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Dietary allicin reduces transformation of L-carnitine to TMAO through impact on gut microbiota
Abstract
Trimethylamine N-oxide (TMAO) was recently discovered as a novel and independent risk factor for promoting atherosclerosis while it has been found to be generated from dietary carnitine through metabolism of gut microbiota for decades. Antibiotics were found to successfully inhibit the pathway of gut microbiota-dependent TMAO formation, as well as prevention of atherosclerosis. However, the side effects and resistance potential of antibiotics limit their potential application. Allicin is a well-established antimicrobial phytochemical naturally found in fresh blended garlic and easily acquired from diet. Here we demonstrated that the plasma TMAO levels in C57BL/6 mice fed with dietary carnitine were 4-22 times greater than that in the control chow diet group during carnitine challenge test. Interestingly, the differences of plasma TMAO level were not seen when comparing mice in carnitine plus allicin diet group with the control chow diet group. The results of this study suggest that dietary allicin may be capable of protecting the host from producing TMAO when carnitine is consumed through its impact on gut microbiota. Allicin and dietary fresh garlic containing allicin may be used as functional foods for the prevention of atherosclerosis.
... Carnitine monooxygenase activity under low oxygen conditions 34 The human intestinal tract encompasses a steep oxygen gradient. It was demonstrated that the oxygen 35 concentration drops along the radial axis from the intestinal submucosa to the lumen. ...
... on gut microbiota has been described (34). Under conditions of the present investigation, an IC 50 of 61 µM 8 was determined and a clearly time-dependent inhibitory effect was demonstrated. ...
... Protein concentrations 32 33 The concentration of purified YeaX and YeaW was determined using Bradford reagent (Sigma-Aldrich) 34 according to the manufacturer's instructions with bovine serum albumin as a standard. ...
Gut microbial production of trimethylamine (TMA) from L-carnitine is directly linked to cardiovascular disease. TMA formation is facilitated by carnitine monooxygenase which was proposed as a target for the development of new cardioprotective compounds. Therefore, the molecular understanding of the two-component Rieske-type enzyme from E. coli was intended. The redox cofactors of the reductase YeaX (FMN, plant-type [2Fe-2S] cluster) and of the oxygenase YeaW (Rieske-type [2Fe-2S] and mononuclear [Fe] center) were identified. Compounds meldonium and the garlic-derived molecule allicin were recently shown to suppress microbiota-dependent TMA formation. Based on two independent carnitine monooxygenase activity assays, enzyme inhibition by meldonium or allicin was demonstrated. Subsequently, the molecular interplay of the reductase YeaX and the oxygenase YeaW was addressed. Chimeric carnitine monooxygenase activity was efficiently reconstituted by combining YeaX (or YeaW) with the orthologous oxygenase CntA (or reductase CntB) from Acinetobacter baumannii. Partial conservation of the reductase/oxygenase docking interface was concluded. A structure guided mutagenesis approach was used to further investigate the interaction and electron transfer between YeaX and YeaW. Based on AlphaFold structure predictions, a total of 28 site-directed variants of YeaX and YeaW were kinetically analyzed. Functional relevance of YeaX residues Arg271, Lys313 and Asp320 was concluded. Concerning YeaW, a docking surface centered around residues Arg83, Lys104 and Lys117 was hypothesized. The presented results might contribute to the development of TMA-lowering strategies that could reduce the risk for cardiovascular disease.
... Recently, allicin was reported to exhibit a modulatory effect on the gut microbiota and reduced hepatic steatosis 38,39 . Additionally, our previous pilot study showed that allicin supplementation shaped the gut microbiota composition and reduced TMAO production by the gut microbiota in mice subject to moderate carnitine consumption (0.02% ʟ-carnitine) 40 . However, the role of raw garlic with allicin in improving cardiovascular phenotypes via gut microbiota modulation has not been fully elucidated. ...
... Allicin potentially inhibited the gut microbiota-host-derived TMA and TMAO in C57BL/6 J mice fed with high concentration (1.3%) of ʟ-carnitine, which is consistent with the results of our previous study in which a daily dosage (0.02%) of ʟ-carnitine was administered 40 . In the murine study, ʟ-carnitine intake was the principal factor affecting the overall gut microbiota composition compared with allicin or DMB intervention. ...
... Information on the resources is provided in Supplementary Table 2. Allicin synthesis, purification, and identification were based on our laboratory protocol 39,40,55 . The purity of allicin was >97%; it was dissolved in 0.5% carboxymethyl cellulose (CMC) and stored at −80°C before administration to the mice. ...
Cardiovascular disease (CVD) is strongly associated with the gut microbiota and its metabolites, including trimethylamine- N -oxide (TMAO), formed from metaorganismal metabolism of ʟ-carnitine. Raw garlic juice, with allicin as its primary compound, exhibits considerable effects on the gut microbiota. This study validated the benefits of raw garlic juice against CVD risk via modulation of the gut microbiota and its metabolites. Allicin supplementation significantly decreased serum TMAO in ʟ-carnitine-fed C57BL/6 J mice, reduced aortic lesions, and altered the fecal microbiota in carnitine-induced, atherosclerosis-prone, apolipoprotein E-deficient (ApoE −/− ) mice. In human subjects exhibiting high-TMAO production, raw garlic juice intake for a week reduced TMAO formation, improved gut microbial diversity, and increased the relative abundances of beneficial bacteria. In in vitro and ex vivo studies, raw garlic juice and allicin inhibited γ-butyrobetaine (γBB) and trimethylamine production by the gut microbiota. Thus, raw garlic juice and allicin can potentially prevent cardiovascular disease by decreasing TMAO production via gut microbiota modulation.
... 34,35 Additionally, our previous pilot study showed that allicin supplementation shaped the gut microbiota composition and reduced TMAO production by the gut microbiota in mice subjected to moderate carnitine consumption (0.02 %carnitine). 36 However, the role of raw garlic with allicin in improving cardiovascular phenotypes via gut microbiota modulation has not been fully elucidated. Therefore, in this study, we aimed to investigate the effect of allicin and raw garlic in modulating both the function and composition of the gut microbiota for cardiovascular protection. ...
... Allicin supplementation in C57BL/6J mice fed a high concentration (1.3 %) of -carnitine demonstrated that the primary compound in raw garlic juice, allicin, potentially inhibited the gut microbiota-and liverderived TMA and TMAO in circulation, which is consistent with the results of our previous study, in which mice were administered a daily dosage (0.02 %) of -carnitine. 36 In the murine study, -carnitine intake was the principal factor affecting the overall gut microbiota composition compared with allicin or DMB intervention. The TMAO-reducing effect of allicin is probably based on its broad-spectrum antimicrobial activities. ...
... Allicin synthesis, puri cation, and identi cation were based on our laboratory protocol. 35,36,48 The purity of allicin was more than 97 %; it was dissolved in 0.5 % carboxymethyl cellulose (CMC) and stored at −80°C before administration to the mice. ...
Cardiovascular disease (CVD) is strongly associated with the gut microbiota and its metabolites, including trimethylamine- N -oxide (TMAO) formed from ʟ-carnitine. Raw garlic juice, with allicin as its primary compound, has been shown to powerfully impact the gut microbiota. This study validated the benefits of raw garlic juice against CVD risk via modulation of the gut microbiota and its metabolites. Allicin supplementation significantly decreased serum TMAO in ʟ-carnitine-fed C57BL/6J mice. It also reduced aortic lesions and altered the fecal microbiota in carnitine-induced, atherosclerosis-prone, apolipoprotein E-deficient mice. In human subjects exhibiting high TMAO production, raw garlic juice intake for a week reduced TMAO formation, improved gut microbial diversity, and increased the relative abundances of beneficial bacteria. In in vitro study, raw garlic juice inhibited γ-butyrobetaine (γBB) and trimethylamine (TMA) production by the gut microbiota. Thus, raw garlic juice can potentially prevent cardiovascular disease by decreasing TMAO production through gut microbiota modulation.
... In fact, the effect of naturally occurring plant compounds on TMAO or trimethylamine (TMA) formation has been investigated in animal models and in vitro. Phytochemicals were found to reduce TMAO formation through modulation of the gut microbiota in mouse models [30,31], and polyphenol-rich plant-based foods were found to reduce the biotransformation of choline and carnitine into TMA in a colonic in vitro model [32]. However, in the latter study, carbohydrates, predominantly in the form of free sugars, possibly caused the main effect [32]. ...
... However, in the latter study, carbohydrates, predominantly in the form of free sugars, possibly caused the main effect [32]. Wu et al. (2015) found that the addition of a food-derived antimicrobial compound, such as allicin found in garlic, can prevent modulation of the gut microbiota induced by a carnitine-enriched diet [31]. Additionally, the structural choline analog, 3,3-dimethyl-1-butanol (DMB), naturally found in foods, such as cold-pressed extra virgin oil, grape seed oil, and some balsamic vinegars, was able to inhibit microbial TMA lyase activity, thereby preventing TMA production [33]. ...
... However, in the latter study, carbohydrates, predominantly in the form of free sugars, possibly caused the main effect [32]. Wu et al. (2015) found that the addition of a food-derived antimicrobial compound, such as allicin found in garlic, can prevent modulation of the gut microbiota induced by a carnitine-enriched diet [31]. Additionally, the structural choline analog, 3,3-dimethyl-1-butanol (DMB), naturally found in foods, such as cold-pressed extra virgin oil, grape seed oil, and some balsamic vinegars, was able to inhibit microbial TMA lyase activity, thereby preventing TMA production [33]. ...
Red meat has been associated with an increased cardiovascular disease (CVD) risk, possibly through gut microbial-derived trimethylamine-N-oxide (TMAO). However, previous reports are conflicting, and influences from the background diet may modulate the impact of meat consumption. This study investigated the effect of red and white meat intake combined with two different background diets on urinary TMAO concentration and its association with the colon microbiome in addition to apparent hepatic TMAO-related activity. For 4 weeks, 32 pigs were fed chicken or red and processed meat combined with a prudent or western background diet. 1H NMR-based metabolomics analysis was conducted on urine samples and hepatic mRNA expression of TMAO-related genes determined. Lower urinary TMAO concentrations were observed after intake of red and processed meat when consumed with a prudent compared to a western background diet. In addition, correlation analyses between urinary TMAO concentrations and relative abundance of colon bacterial groups suggested an association between TMAO and specific bacterial taxa. Diet did not affect the hepatic mRNA expression of genes related to TMAO formation. The results suggest that meat-induced TMAO formation is regulated by mechanisms other than alterations at the hepatic gene expression level, possibly involving modulations of the gut microbiota.
... These common microorganisms contribute to TMA formation in the colon through the precursors L-carnitine and phosphatidylcholine [14]. Previous studies have observed that plant origin substances can act as prebiotics and reduce the transformation of L-carnitine to TMA through their action on the colonic microbiota [15]. Considering this, the gut microbiota could be modulated to restore the balance between beneficial and detrimental microorganisms regarding TMA and TMAO production. ...
... Transplanted mice were randomly assigned to five experimental groups, with eight animals per group (n = 8), in a cage at the beginning of the study, based on a previous similar study [15]: (1) control group, mice without L-carnitine supplementation or essential oil administration; (2) carnitine group, mice with L-carnitine supplementation but not essential oil administration; (3) savory group, mice with L-carnitine supplementation and savory essential oil; (4) parsley group, mice with L-carnitine supplementation and parsley essential oil; and (5) rosemary group, mice with L-carnitine supplementation and rosemary essential oil. No criteria were used for including and excluding animals during the experiment. ...
Ischemic heart disease (IHD) and type-2 diabetes mellitus (T2DM) remain major health problems worldwide and commonly coexist in individuals. Gut microbial metabolites, such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), have been linked to cardiovascular and metabolic diseases. Previous studies have reported dysbiosis in the gut microbiota of these patients and the prebiotic effects of some components of the Mediterranean diet. Essential oil emulsions of savory (Satureja hortensis), parsley (Petroselinum crispum) and rosemary (Rosmarinus officinalis) were assessed as nutraceuticals and prebiotics in IHD and T2DM. Humanized mice harboring gut microbiota derived from that of patients with IHD and T2DM were supplemented with L-carnitine and orally treated with essential oil emulsions for 40 days. We assessed the effects on gut microbiota composition and abundance, microbial metabolites and plasma markers of cardiovascular disease, inflammation and oxidative stress. Our results showed that essential oil emulsions in mice supplemented with L-carnitine have prebiotic effects on beneficial commensal bacteria, mainly Lactobacillus genus. There was a decrease in plasma TMAO and an increase in fecal SCFAs levels in mice treated with parsley and rosemary essential oils. Thrombomodulin levels were increased in mice treated with savory and parsley essential oils. While mice treated with parsley and rosemary essential oils showed a decrease in plasma cytokines (INFɣ, TNFα, IL-12p70 and IL-22); savory essential oil was associated with increased levels of chemokines (CXCL1, CCL2 and CCL11). Finally, there was a decrease in protein carbonyls and pentosidine according to the essential oil emulsion. These results suggest that changes in the gut microbiota induced by essential oils of parsley, savory and rosemary as prebiotics could differentially regulate cardiovascular and metabolic factors, which highlights the potential of these nutraceuticals for reducing IHD risk in patients affected by T2DM.
... This overall improves the cardiovascular health of an individual. Allicin found in garlic is able to inhibit the formation of trimethylamine-N-oxide (TMAO) [70] . The gut microbiota forms TMAO through the metabolism of carnitine, and it acts to promote atherosclerosis [70] . ...
... Allicin found in garlic is able to inhibit the formation of trimethylamine-N-oxide (TMAO) [70] . The gut microbiota forms TMAO through the metabolism of carnitine, and it acts to promote atherosclerosis [70] . Hence, we can deduce that consumption of garlic in the long term will decrease the risk of atherosclerosis. ...
Garlic is a herb and has been used as a spice with a long history in different types of cuisine. Garlic and its components are believed to be able to bring benefits to the health of an individual. The gut microbiota is closely related to an individual's health, and garlic is shown to have an effect on the gut microbiota as well. Hence, this literature review aims to portray the uses of garlic and its bioactive constituents on human health, particularly looking at how it modulates the gut microbiota and subsequently affects an individual's health directly or indirectly. These studies have shown the ameliorative effects of garlic and its bioactive constituents on various chronic diseases, including hypertension, diabetes mellitus, hyperlipidaemia and liver diseases.
... 14,121,122 Allicin supplementation also reportedly altered the gut-microbiota composition and decreased TMAO generation by the gut microbiota in mice administered carnitine (Table 4). 123 Allicin relieves atherosclerosis in ApoE À/À , and raw garlic juice (containing allicin) reduces plasma TMAO and increases beneficial bacteria, including Faecalibacterium prausnitzii and Akkermansia spp. in humans. ...
... Study model Important finding Effect on gut microbiota and their metabolites Raw garlic (Allicin) 123 Male C57BL/6 mice fed with 0.02% ʟ-carnitine in the drinking water and supplemented with 10 mg/kg/day allicin by oral gavage. ...
Dietary nutrients are associated with the development of cardiovascular disease (CVD) both through traditional pathways (inducing hyperlipidemia and chronic inflammation) and through the emergence of a metaorganism-pathogenesis pathway (through the gut microbiota, its metabolites, and host). Several molecules from food play an important role as CVD risk-factor precursors either themselves or through the metabolism of the gut microbiome. Animal-based dietary proteins are the primary source of CVD risk-factor precursors; however, some plants also possess these precursors, though at relatively low levels compared with animal-source food products. Various medications have been developed to treat CVD through the gut-microbiota–circulation axis, and they exhibit potent effects in CVD treatment. Nevertheless, such medicines are still being improved, and there are many research gaps that need to be addressed. Furthermore, some medications have unpleasant or adverse effects. Numerous foods and herbs impart beneficial effects upon health and disease. In the past decade, many studies have focused on treating and preventing CVD by modulating the gut microbiota and their metabolites. This review provides an overview of the available information, summarizes current research related to the gut-microbiota–heart axis, enumerates the foods and herbs that are CVD-risk precursors, and illustrates how metabolites become CVD risk factors through the metabolism of gut microbiota. Moreover, we present perspectives on the application of foods and herbs—including prebiotics, probiotics, synbiotics, postbiotics, and antibiotic-like substances—as CVD prevention agents to modulate gut microbiota by inhibiting gut-derived CVD risk factors.
Taxonomy (classification by EVISE)
Cardiovascular disease, gut microbiota, herbal medicine, preventive medicine, dietary therapy, nutrition supplements.
... While various mechanisms of action have been proposed, an emerging theory is that phytochemicals may also mediate their cardioprotective effects in part through the inhibition of TMAO formation [10]. Some intervention strategies based on phytochemical supplementation (i.e., allicin and 3,3-dimethyl-1-butanol) have been successful to reduce TMA and/or TMAO formation in animal models [11,14,15] and humans [16,17]. High-throughput inhibitor screening studies have demonstrated their utility for quickly identifying synthetic CutC/D inhibitors [18], and these types of approaches could be used to narrow down a vast array of hundreds or thousands of potential phytochemicals to a few promising candidate compounds with inhibitory activity to be subsequently tested in vivo. ...
... The inhibition of TMAO formation can be achieved by reducing the conversion of choline and carnitine to TMA in the gut, thus reducing the amount of TMA available for oxidation to TMAO [11]. Phytochemicals are known to exert cardioprotective and anti-atherosclerotic functions [13,27], and some of these compounds have also been reported to reduce TMAO formation [11,[14][15][16][17]. It is thus possible that phytochemical inhibition of TMA formation may be an effective cardioprotective mechanism via lowering TMAO. ...
Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of
pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). A reduction in TMA formation has shown cardioprotective effects, and some phytochemicals may reduce TMA formation. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study the inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20% fecal slurry (1:10 in PBS), 100 µM choline, and 12 h fermentation. Additionally, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50% reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80–90% TMA production inhibition), with IC50 around 5 mM. Neither DMB nor gallic acid or chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA-lyase activity or expression.
... While various mechanisms of action have been proposed, an emerging theory is that phytochemicals may also mediate their cardioprotective effect in part through the inhibition of TMAO formation [10]. Some intervention strategies based on phytochemical supplementation (i.e., allicin and 3,3-dimethyl-1butanol) have been successful to reduce TMA and/or TMAO formation in animal models [11,14,15] and humans [16,17]. High throughput inhibitor screening studies have demonstrated their utility for quickly identifying synthetic CutC/D inhibitors [18], and these type of approaches could be used to narrow down a vast array of hundreds or thousands of potential phytochemicals to a few promising candidate compounds with inhibitory activity to be subsequently tested in vivo. ...
... The inhibition of TMAO formation can be achieved by reducing the conversion of choline and carnitine to TMA in the gut, thus reducing the amount of TMA available for oxidation to TMAO [11]. Phytochemicals are known to exert cardioprotective and anti-atherosclerotic functions [13,27], and some of these compounds have also been reported to reduce TMAO formation [11,[14][15][16][17]. It is thus possible that phytochemical inhibition of TMA formation may be an effective cardioprotective mechanism via lowering TMAO. ...
Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). Reduction of TMA formation has been shown to provide to cardioprotective effects, and some phytochemicals may produce such reduction. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20 % fecal slurry (1:10 in PBS), 100 M choline, and 12 h fermentation. Also, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50 % reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80 -90 % in. TMA production inhibition), with IC50 around 5 mM. Nor DMB neither gallic acid and chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA lyase activity or expression.
... Taking only this information into consideration, the reduction of red meat within a healthy diet should be recommended. However, carnitine exerts positive effects as mentioned above, and most importantly, the TMAO formed from carnitine is largely dependent on the microbial population of the gut and the presence of dietary substances with ability to inhibit the TMA synthesis from carnitine, such as resveratrol or allicin (Chen et al., 2016;Wu et al., 2015). Other authors have found different TMAO blood levels in diabetic and non-diabetic cardiac patients, being strongly associated with different patterns of the intestinal microbiota (Sanchez-Alcoholado et al., 2017). ...
... This antioxidant and antimicrobial substance achieved this reduction by modulating the microbiota, inhibiting commensal microbial TMA producers and increasing levels of the genera Lactobacillus and Bifidobacterium (Chen et al., 2016). Similarly, allicin, a potent antimicrobial found in garlic, significantly reduced TMAO blood levels in mice fed with carnitine, through gut microbiota modulation (Wu et al., 2015). ...
The assessment of the actual contribution of red or processed meat to increasing the risk of suffering cardiovascular diseases (CVD) requires identification of specific harmful components and their underlying pathological mechanisms. In regards to CVD, meat lipids and their oxidation products have been recurrently studied due to their implications on lipid metabolism, hypercholesterolemia, obesity, and risk of suffering vascular events such as stroke. The impact of excess NaCl intake on increasing blood pressure is well-established and processed meat products have been recognized as a major contributor to dietary sodium in developed countries. Recent evidence has also suggested carnitine from red meat, as a precursor for trimethylamine-N-oxide, which has been shown to cause atherosclerosis, may increase the risk of suffering CVD in experimental animals. The present review aims to provide an updated overview, including evidence, controversies and unresolved questions on both the epidemiology and mechanisms relating red and processed meat consumption to CVD.
... For example, consumption of phytochemicals, such as allicin in garlic and resveratrol in red wine and grapes, may change the composition of the gut microbiota and, in association, reduce the effect of TMAO. Wu et al. (2015) examined the effect of allicin (50 mg) on carnitine diet using C57Bl/6 mice [144]. Oral feeding of allicin reduced the carnitine-induced plasma level of TMAO to that of standard chow, concomitant with a change in the taxa of the gut microbiota. ...
... For example, consumption of phytochemicals, such as allicin in garlic and resveratrol in red wine and grapes, may change the composition of the gut microbiota and, in association, reduce the effect of TMAO. Wu et al. (2015) examined the effect of allicin (50 mg) on carnitine diet using C57Bl/6 mice [144]. Oral feeding of allicin reduced the carnitine-induced plasma level of TMAO to that of standard chow, concomitant with a change in the taxa of the gut microbiota. ...
Diet and microbiota each have a direct impact on many chronic, inflammatory, and metabolic diseases. As the field develops, a new perspective is emerging. The effects of diet may depend on the microbiota composition of the intestine. A diet that is rich in choline, red meat, dairy, or egg may promote the growth, or change the composition, of microbial species. The microbiota, in turn, may produce metabolites that increase the risk of cardiovascular disease. This article reviews our current understanding of the effects of the molecule trimethylamine-N-oxide (TMAO) obtained from food or produced by the microbiota. We review the mechanisms of actions of TMAO, and studies that associate it with cardiovascular and chronic kidney diseases. We introduce a novel concept: TMAO is one among a group of selective uremic toxins that may rise to high levels in the circulation or accumulate in various organs. Based on this information, we evaluate how TMAO may harm, by exacerbating inflammation, or may protect, by attenuating amyloid formation, in autoimmune diseases such as rheumatoid arthritis.
... However, the administration of allicin, a component of garlic, was able to reduce the content of Robinsoniella psoriasis in mice fed with dietary carnitine. This suggests that certain functional foods and their active compounds can have effects on specific bacteria and subsequently influence metabolic syndrome markers [87]. ...
It is now widely recognized that gut microbiota plays a critical role not only in the development and progression of diseases, but also in its susceptibility to dietary patterns, food composition, and nutritional intake. In this comprehensive review, we have compiled the latest findings on the effects of food nutrients and bioactive compounds on the gut microbiota. The research indicates that certain components, such as unsaturated fatty acids, dietary fiber, and protein have a significant impact on the composition of bile salts and short-chain fatty acids through catabolic processes, thereby influencing the gut microbiota. Additionally, these compounds also have an effect on the ratio of Firmicutes to Bacteroides, as well as the abundance of specific species like Akkermansia muciniphila. The gut microbiota has been found to play a role in altering the absorption and metabolism of nutrients, bioactive compounds, and drugs, adding another layer of complexity to the interaction between food and gut microbiota, which often requires long-term adaptation to yield substantial outcomes. In conclusion, understanding the relationship between food compounds and gut microbiota can offer valuable insights into the potential therapeutic applications of food and dietary interventions in various diseases and health conditions.
... Additionally, essential oils or vehicle were administered daily by gavage in a final volume of 100 µL. The dosages were established as previously reported [29], with an initial basal dosage of 10 mg/kg/day. Subsequently, this basal dosage was increased to 20 mg/kg/day to investigate potential dose-dependent effects of the essential oils. ...
Essential oils sourced from herbs commonly used in the Mediterranean diet have demonstrated advantageous attributes as nutraceuticals and prebiotics within a model of severe cardiometabolic disorder. The primary objective of this study was to assess the influences exerted by essential oils derived from thyme (Thymus vulgaris) and oregano (Origanum vulgare) via a comprehensive multi-omics approach within a gnotobiotic murine model featuring colonic microbiota acquired from patients diagnosed with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM). Our findings demonstrated prebiotic and potential antioxidant effects elicited by these essential oils. We observed a substantial increase in the relative abundance of the Lactobacillus genus in the gut microbiota, accompanied by higher levels of short-chain fatty acids and a reduction in trimethylamine N-oxide levels and protein oxidation in the plasma. Moreover, functional enrichment analysis of the cardiac tissue proteome unveiled an over-representation of pathways related to mitochondrial function, oxidative stress, and cardiac contraction. These findings provide compelling evidence of the prebiotic and antioxidant actions of thyme- and oregano-derived essential oils, which extend to cardiac function. These results encourage further investigation into the promising utility of essential oils derived from herbs commonly used in the Mediterranean diet as potential nutraceutical interventions for mitigating chronic diseases linked to CAD and T2DM.
... [88] ↓: Decrease, ↑: Increase, T2DM: Type 2 diabetes mellitus, CVD: Cardiovascular disease, HFpEF: Heart failure with preserved ejection fraction, HT: Hypertension, HF: Heart failure, CAD: Coronary artery disease, HFrEF: Heart failure reduced ejection fraction, NDM2: Nondiabetes mellitus type 2, ACVD: Atherosclerotic cardiovascular disease, PHTN: Prehypertensive, HMW: High-molecular-weight. Allicin ↓plasma TMAO and influenced gut-microbiota composition [61] absorption. There is evidence to suggest that nutrition and the activity of the gut microbiota are closely linked and can be coordinated. ...
Cardiovascular disease (CVD) remains the most common cause of death worldwide and has become a public health concern. The proven notable risk factors for CVD are atherosclerosis, hypertension, diabetes, dyslipidemia, inflammation, and some genetic defects. However, research has shown a correlation between metabolic health, gut microbiota, and dietary risk factors. The gut microbiota makes an important contribution to human functional metabolic pathways by contributing enzymes that are not encoded by the human genome, for instance, the breakdown of polysaccharides, polyphenols and vitamins synthesis. TMAO and SCFAs, human gut microbiota compounds, have respective immunomodulatory and pro-inflammatory effects. Choline and l-carnitine are abundant in high-fat diets and are transformed into TMA by gut bacteria. The liver's phase of metabolism then changes TMA into TMAO. In turn, TMAO promotes the activation of macrophages, damages vascular endothelium, and results in CVD-however, dysbiosis decreases SCFAs and bile acids, which raises intestinal permeability. Congestion in the portal vein, a drop in cardiac output, a reduction in intestinal perfusion, and intestinal leakage are all caused by heart failure. These factors induce systemic inflammation by increasing intestinal leakage. By raising CRP and pro-inflammatory reactions, human gut dysbiosis and elevated TMAO levels promote the development of arterial plaque, hasten the beginning of atherosclerosis, and raise the risk of CAD. A healthy symbiosis between the gut microbiota and host is a key factor in shaping the biochemical profile of the diet, therefore which are crucial for maintaining the intestinal epithelial barrier, growing mucosa, reducing inflammation, and controlling blood pressure.
... Several natural products have been widely recognized to modulate gut microbiota and influence health in human in vivo and in vitro studies. For instance, polyphenol-rich diets [81], an edible leguminous mung bean (Vignaradiata L.) supplement [82], blueberry proanthocyanidins [83], a wasabi supplement [84], polyphenols rich in high-quality extra-virgin olive oil in combination with a Mediterranean diet [85], sulfated polysaccharides from the flesh of Callosobruchus chinensis [86], cranberry (Vaccinium macrocarpon) fruits [87], apple procyanidin polyphenols [88], resveratrol polyphenol [89], a supplement mixture of quercetin and catechin polyphenols [90], dietary fiber from Apple-derived pectin [91], a dietary quercetin [92], and the phytochemical allicin phytochemical from garlic [93] all modulate gut microbiota and confer improvements in metabolic health profile, as well as anti-arthrosclerosis effects. This shows the promising role of natural products in stroke prevention. ...
The human microbiota-gut-brain axis has an enormous role in the maintenance of homeostasis and health. Over the last two decades, it has received concerted research attention and focus due to a rapidly emerging volume of evidence that has established that impairment within the microbiota-gut-brain axis contributes to the development and progression of various diseases. Stroke is one of the entities identified to be associated with microbiota-gut-brain axis impairment. Currently, there are still limitations in the clinical treatment of stroke, and the presence of a non-nervous factor from gut microbiota that can alter the course of stroke presents a novel strategy towards the search for a therapeutic silver bullet against stroke. Hence, the aim herein, was to focus on the involvement of microbiota-gut-brain axis impairment in the pathogenesis stroke as well as elucidate its implications as a potent therapeutic target against stroke. The findings of studies to date have revealed and extended the role microbiota-gut-brain axis impairment in the pathogenesis of stroke, and studies have identified from both clinical and pre-clinical perspectives targets within the microbiota-gut-brain axis and successfully modulated the outcome of stroke. It was concluded that the microbiota-gut-brain axis stands as potent target to salvage the neurons in the ischemic penumbra for the treatment of stroke. Assessment of the microbiota profile and its metabolites status holds enormous clinical potentials as a non-invasive indicator for the early diagnosis and prognosis of stroke.
... Garlic has been used in food from ancient times. It contains allicin which has been confirmed to alter the gut microflora, and it reduces TMAO generation [72]. The colonization of Faecalibacterium prausnitzii and Akkermansia spp. is found to be promoted by administering raw garlic juice [68]. ...
The human gut is colonized by a variety of microorganisms especially bacteria. There are multiple evidences that gut microflora dysbiosis is a novel risk factor for development of various intestine-related diseases such as irritable bowel syndrome and inflammatory bowel disease as well as nonintestinal diseases including obesity, type II diabetes, and cardiovascular diseases. A mutual relationship among the host’s immune system and the metabolites produced by the gut microflora, including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acids, is present. Alterations in the host-microbial interaction lead to impaired homeostasis and thus contribute towards the activation of several pathways that causes progression of cardiovascular diseases. This review summarizes the role of gut microflora dysbiosis in the development and progression of atherosclerosis, coronary artery disease, and hypertension. Dysbiosis has been implicated in the pathogenesis of atherosclerosis by TLR activation, intracellular Ca2+ release, FXR-induced signalling, and decreased removal of cholesterol from peripheral macrophages, while in hypertension the mechanism involved is prolonged haemodynamic effects of angiotensin-II and oxLDL-induced hypertension. In fact, CVDs are the leading cause of mortality across the globe; thus, targeting the gut microflora in the treatment of these diseases along with the conventional therapy can markedly reduce the cardiovascular disease burden. The gut microbiota-targeted treatment including prebiotics, probiotics, and postbiotics can be therapeutically beneficial. In future, the heart-gut axis can be presented as a novel and clinically relevant area for research.
... Some studies have also found that in the setting of dysglycaemia, the ratio of Firmicutes to Bacteroidetes increased, as did the abundances of Ruminococcus/Clostridium and Barnesiellaceae/E. coli/Proteobacteria [28][29][30]. However, the abundance of butyric acid-producing bacteria and the ratio of Bacteroides/Verrucomicrobiae decreased substantially [31]. ...
Background:
This paper aimed to examine the effects of probiotics on eight factors in the prediabetic population by meta-analysis, namely, fasting blood glucose (FBG), glycated haemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the mechanisms of action are summarized from the existing studies.
Methods:
Seven databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed, CNKI, and Wanfang Med) were searched until March 2022. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model to observe the efficacy of probiotic supplementation on the included indicators.
Results:
Seven publications with a total of 460 patients were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HbA1c (WMD, -0.07; 95% CI -0.11, -0.03; P = 0.001), QUICKI (WMD, 0.01; 95% CI 0.00, 0.02; P = 0.04), TC (SMD, -0.28; 95% CI -0.53, -0.22; P = 0.03), TG (SMD, -0.26; 95% CI -0.52, -0.01; P = 0.04), and LDL-C (WMD, -8.94; 95% CI -14.91, -2.97; P = 0.003) compared to levels in the placebo group. The effects on FBG (WMD, -0.53; 95% CI -2.31, 1.25; P = 0.56), HOMA-IR (WMD, -0.21; 95% CI -0.45, 0.04; P = 0.10), and HDL-C (WMD, 2.05; 95% CI -0.28, 4.38; P = 0.08) were not different from those of the placebo group.
Conclusion:
The present study clearly indicated that probiotics may fulfil an important role in the regulation of HbA1c, QUICKI, TC, TG and LDL-C in patients with prediabetes. In addition, based on existing studies, we concluded that probiotics may regulate blood glucose homeostasis in a variety of ways.
Trial registration:
This meta-analysis has been registered at PROSPERO with ID: CRD42022321995.
... Resveratrol (RSV) reduces TMAO-induced atherosclerosis by lowering TMAO levels and enhancing hepatic bile acid synthesis through gut microbiota remodeling [116]. Antimicrobial phytochemicals, such as allicin, a dietary dosage derived from garlic, effectively neutralize the metabolic ability of gut microbiota to produce TMAO-induced by L-carnitine intake [117]. Luhong granules, a complex blend of herbs, flowers, animal parts, seeds, and roots, prolong ventricular remodeling after myocardial infarction by lowering TMAO and LPS levels in the bloodstream by increasing the gut microflora and intestinal barrier function [118]. ...
Atherosclerosis (AS) is the common pathological underpinning of numerous cardiovascular illnesses (CVDs), and it is the leading cause of death worldwide. In recent years, researchers have begun to recognize the importance of gut microbiota in AS. Gut microbial dysbiosis has been reported to be connected with various CVDs. Moreover, dietary choline, betaine, and L-carnitine produce trimethylamine N-oxide (TMAO), a key gut microbe-dependent metabolite. Multiple studies have found a link between plasma TMAO levels and the likelihood of developing AS. The mechanism underlying this link, however, is still unknown. In this chapter, we discuss the TMAO-mediated mechanisms of atherosclerotic CVD from the perspectives of dietary patterns and gut microbial metabolism. Finally, we explain how TMAO has emerged as a novel therapeutic target for CVDs, as well as many treatment options for lowering TMAO levels that are currently being investigated, such as medications, dietary changes, probiotics, and so on.
... Moreover, allicin prevented trimethylamine N-oxide (TMAO) formation after carnitine intake by modulating gut microbiota (W.-K. Wu et al., 2015). TMAO is a gut microbiota-liver metabolite that may aggravate steatosis by modulating bile acid metabolism (Tan et al., 2019). ...
This systematic review and meta-analysis study was conducted to summarize the effects of garlic or its major components on hepatic triglyceride and cholesterol content, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, and liver weight. We searched PubMed, Embase, Scopus, and Web of Knowledge databases. Data were pooled, and standardized mean difference (SMD) and 95% confidence intervals (CI) were estimated using the random-effect model. Out of 958 reports, 28 articles were eligible, of which 22 studies were included in the meta-analysis. Most of the included studies demonstrated the beneficial effects of garlic on hepatic histopathological features. The pooled results showed that garlic significantly decreased hepatic triglyceride and cholesterol, ALT, AST, and liver weight. The certainty of the estimates was very low to low according to GRADE. In conclusion, our study demonstrated amelioration of hepatic histopathological characteristics, hepatic lipid content, serum liver enzymes, and liver weight following garlic administration.
... Supplementing feed of farrowing sows and European bass with GO decreased pathogenic microbes from the gut microbiome (Rimoldi et al., 2020;Satora et al., 2020). Allicin treatment prevented high carnitine diet-induced dysbiosis to lower the atherosclerosis risk factor trimethylamine N-oxide that is produced by the gut microbiome (Wu W. K. et al., 2015). Oral administration of alliin, precursor of allicin, to rats resulted in decreasing the relative abundance of only Allobaculum genus in the cecum . ...
Garlic ( Allium sativum ), a popular food spice and flavoring agent, has also been used traditionally to treat various ailments especially bacterial infections for centuries in various cultures around the world. The principal phytochemicals that exhibit antibacterial activity are oil-soluble organosulfur compounds that include allicin, ajoenes, and allyl sulfides. The organosulfur compounds of garlic exhibit a range of antibacterial properties such as bactericidal, antibiofilm, antitoxin, and anti-quorum sensing activity against a wide range of bacteria including multi-drug resistant (MDR) strains. The reactive organosulfur compounds form disulfide bonds with free sulfhydryl groups of enzymes and compromise the integrity of the bacterial membrane. The World Health Organization (WHO) has recognized the development of antibiotic resistance as a global health concern and emphasizes antibiotic stewardship along with the urgent need to develop novel antibiotics. Multiple antibacterial effects of organosulfur compounds provide an excellent framework to develop them into novel antibiotics. The review provides a focused and comprehensive portrait of the status of garlic and its compounds as antibacterial agents. In addition, the emerging role of new technologies to harness the potential of garlic as a novel antibacterial agent is discussed.
... Conversely, according to Latkovskis et al. [93], a reduction of TMAO urinary was associated with increase plasma TMAO concentration, which may not be beneficial. Besides, allicin (2-propene-1-sulfinothioic acid S-2) found in garlic was efficient in reducing TMAO levels by acting as a natural antibiotic in the gut microbiota [94]. ...
Background
Trimethylamine N-oxide (TMAO) is a metabolite that has attracted attention due to its positive association with several chronic non-communicable diseases such as insulin resistance, atherosclerotic plaque formation, diabetes, cancer, heart failure, hypertension, chronic kidney disease, liver steatosis, cardiac fibrosis, endothelial injury, neural degeneration and Alzheimer's disease. TMAO production results from the fermentation by the gut microbiota of dietary nutrients such as choline and carnitine, which are transformed to trimethylamine (TMA) and converted into TMAO in the liver by flavin-containing monooxygenase 1 and 3 (FMO1 and FMO3). Considering that TMAO is involved in the development of many chronic diseases, strategies have been found to enhance a healthy gut microbiota. In this context, some studies have shown that nutrients and bioactive compounds from food can modulate the gut microbiota and possibly reduce TMAO production.Objective
This review has as main objective to discuss the studies that demonstrated the effects of food on the reduction of this harmful metabolite.Methods
All relevant articles until November 2020 were included. The articles were searched in Medline through PubMed.ResultsBoth the food is eaten acutely and chronically, by altering the nature of the gut microbiota, influencing colonic TMA production. Furthermore, hepatic production of TMAO by the flavin monooxygenases in the liver may also be influenced by phenolic compounds present in foods.Conclusion
The evidence presented in this review shows that TMAO levels can be reduced by some bioactive compounds. However, it is crucial to notice that there is significant variation among the studies. Further clinical studies should be conducted to evaluate these dietary components’ effectiveness, dose, and intervention time on TMAO levels and its precursors.
... Chen et al. [26] and Wk et al. [96] conducted studies in germ-free ApoE À/À mice revealed natural bioactive compounds such as resveratrol and allicin attenuated TMAO-induced atherosclerosis. Another ApoEÀ/À mice study showed lower circulating LPS levels lead to reduced systemic inflammation and decreased atherosclerosis compared to conventionally raised ApoE À/À mice [97]. ...
Human gut microbiota (GM) is a unique ecosystem harboring trillions of microbes, is arguably the largest endocrine and paracrine organ in the body. Microbes residing in human intestine produce several bioactive signaling molecules (BSM), which are transported in the systemic circulation to various organs. Development of heart disease or its acceleration is seen in individuals who have coexisting gastrointestinal disorders. Dysbiosed GM (altered gut microbial composition) produce high levels of harmful BSM such as trimethylamine (TMA)/trimethylamine-N-oxide (TMAO), bile acids (BAs), uremic toxins, lipopolysaccharide (LPS), low concentrations of short chain fatty acids (SCFAs). Intestinal epithelial cells (IECs) in dysbiosed gut synthesize reduced levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), the key regulator of LDL-C clearance. The expression of PCSK9 in IECs depends on the host metabolic status and dietary habits. Decreased production of PCSK9 in the gut may promote imbalance in cholesterol metabolism leading to atherosclerotic cardiovascular disease (ASCVD). In contrast, in the normal gut the optimum production of PCSK9 show a protective effect on the cardiovascular system by regulating low-density lipoprotein receptor (LDLR) expression and apolipoprotein-B-lipoprotein cholesterol biosynthesis. However, a definitive link between the intestine-derived PCSK9 in cholesterol homeostasis and cardiovascular risk remains poorly understood. The objective of this review is to present the current knowledge and discuss the heart-gut-PCSK9 interaction, for a better understanding of the role GM plays in the regulation of cholesterol metabolism. We have presented the available evidences implicating a bidirectional cross-talk between heart and gut in reducing LDL-C through PCSK9, and also highlighted the prospects of GM-targeted treatment strategies for ASCVD prevention.
... For example, dietary allicin, an active antibacterial compound in garlic, can reduce TMAO formation by affecting the gut microbiota. 116 Resveratrol, a polyphenolic plant antitoxin with an anti-inflammatory effect, has been reported to rescue TMAOinduced atherosclerosis by shifting the gut microbiota composition, reducing plasma TMAO levels, and accelerating liver bile acid synthesis. 117 As described above, a key regulator in the TMAO synthesis pathway is FMO3, which rapidly converts TMA to TMAO. ...
An increasing amount of evidence reveals that the gut microbiota is involved in the pathogenesis and progression of various cardiovascular diseases. In patients with heart failure (HF), splanchnic hypoperfusion causes ischemia and intestinal edema, allowing bacterial translocation and bacterial metabolites to enter the blood circulation via an impaired intestinal barrier. This results in local and systemic inflammatory responses. Gut microbe-derived metabolites are implicated in the pathology of multiple diseases, including HF. These landmark findings suggest that gut microbiota influences the host's metabolic health, either directly or indirectly by producing several metabolites. In this review, we mainly discuss a newly identified gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO), which appears to participate in the pathologic processes of HF and can serve as an early warning marker to identify individuals who are at the risk of disease progression. We also discuss the potential of the gut–TMAO–HF axis as a new target for HF treatment and highlight the current controversies and potentially new and exciting directions for future research.
... Reduction in carnitine-induced elevation of plasma TMAO levels in mice, microbiota re-modeling [183]. ...
Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease. However, the relationship between the microbiota production of these components and its impact on these diseases still remains unknown. In this review, we will address which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., the genotype) and diet affect TMA production, and the colonization of these microbes and the reversal of dysbiosis as a therapy for these diseases.
... L-carnitine is present in high levels in red meat, poultry and some dairy products, which is why TMAU sufferers are recommended to avoid these in their diet [60]. Interestingly, allicin, an organosulfur compound obtained from garlic, lowered TMAO levels when supplemented in addition to L-carnitine in male mice [61], an animal model that is a natural knockout for FMO3, and in which FMO1 does not efficiently catalyze the transformation of TMA to TMAO [62]. The mechanism of allicin remains elusive but is hypothesized to be connected to its potential role as a Rieske protein inhibitor, which would reduce carnitine transformation to TMA by bacteria. ...
Trimethylamine (TMA) is a volatile, foul-smelling, diet-derived amine, primarily generated in the colon and metabolized in the liver to its odorless N-oxide (TMAO). In primary trimethylaminuria (TMAU), an inherited deficiency in flavin-containing monooxygenase 3 leads to elevated systemic TMA levels. The excretion of elevated amounts of TMA in sweat, breath, urine and other bodily secretions gives individuals affected by TMAU a smell resembling that of rotten fish. Although the disorder might not seem an important health problem, its social and psychological burden can be devastating. To date, no treatment modifying the disorder exists and only a few pharmacological therapies provide modest and transient benefits. This review provides an overview of investigated TMAU treatments and outlines promising new research directions.
... A study demonstrated that dietary fiber feeding reshaped the intestinal microbial ecology; enhanced the growth of Akkermansia and Bifidobacterium, etc.; and restrained the growth of harmful species to reduce TMA and TMAO metabolism via remodeling of the gut microbiota structure in mice (127). Furthermore, some bioactive molecules from foods, such as allicin, also influence TMA and TMAO production (128). ...
The substantial discrepancy between the strong effects of functional foods and various drugs, especially traditional Chinese medicines (TCMs), and the poor bioavailability of these substances remains a perplexing problem. Understanding the gut microbiota, which acts as an effective bioreactor in the human intestinal tract, provides an opportunity for the redefinition of bioavailability. Here, we discuss four different pathways associated with the role of the gut microbiota in the transformation of parent compounds to beneficial or detrimental small molecules, which can enter the body’s circulatory system and be available to target cells, tissues, and organs. We further describe and propose effective strategies for improving bioavailability and alleviating side effects with the help of the gut microbiota. This review also broadens our perspectives for the discovery of new medicinal components.
... Because 22.4% of alliin was found in the intestine within a period of time (19), it only slightly altered the composition of small intestinal bacteria and subsequently cecal bacteria with no specific phylum and only one genus, Allobaculum, significantly impacted in this experiment. This slight alteration was also because alliin did not convert to allicin due to the absence of an appropriate enzyme (alliinase) in rats or mice (Egenschwind, Eckard, & Kemper, 1992;Guo, Muller, Pentz, Kress, & Siegers, 1990), whereas allicin, the enzymatic hydrolysis product of alliin, was reported to significantly affect several specific gut microbiota (Wu et al., 2015). As a result, alliin supplementation has no effect on the level of sulfate-reducing bacteria in gut microbiota, which mainly reside in the colon because they are acclimated to anoxic habitats (Muyzer & Stams, 2008). ...
Alliin is a natural organosulfur‐containing phytochemical in garlic. It is possible that alliin can regulate the gut microbiota for its strong antimicrobial activity against many pathogens. Here, we assessed whether alliin impacts the distal small intestinal bacteria, hence the cecal microbiota, thus altering the gene expression of colonic epithelial tissues (CETs). Eighty mg/kg alliin was orally administered to rats for 14 days, and the 16S rDNA from small intestinal and cecal microbiota as well as mRNA from CETs were sequenced and analyzed. The results showed that alliin consumption affected microbiota composition in both the small intestine and cecum, although there was only one specific genus, Allobaculum that was significantly altered in the rat cecum. The altered composition of microbiota indirectly impacted 174 genes in the CETs. Specifically, five genes, including RT1‐Ba, RT1‐Bb, Cd80, Madcam1, and Aicda, indicated this consumption related to the intestinal immune network for IgA production.
Practical applications
We firstly reported alliin consumption in vivo potentially affected the intestinal immunity of healthy rats by slightly alteration of microbiota composition in small intestine and cecum. The alteration subsequently amplified, resulting in the change of the colonic epithelial expression of several genes related to the intestinal immune network for IgA production. Hence, we suggested the alliin consumption may potentially affect the immune system of healthy individuals by alteration of gut microbiota and epithelial gene expression.
Overall diet, lifestyle choices, genetic predisposition, and other underlying health conditions may contribute to higher trimethylamine N‐oxide (TMAO) levels and increased cardiovascular risk. This review explores the potential therapeutic ability of RSV to protect against cardiovascular diseases (CVD) and affect TMAO levels. This review considers recent studies on the association of TMAO with CVD. It also examines the sources, mechanisms, and metabolism of TMAO along with TMAO‐induced cardiovascular events. Plant polyphenolic compounds, including resveratrol (RSV), and their cardioprotective mechanism of regulating TMAO levels and modifying gut microbiota are also discussed here. RSV's salient features and bioactive properties in reducing CVD have been evaluated. The close relationship between TMAO and CVD is clearly understood from currently available data, making it a potent biomarker for CVD. Precise investigation, including clinical trials, must be performed to understand RSV's mechanism, dose, effects, and derivatives as a cardioprotectant agent.
Die Schleimhäute spielen eine wichtige Rolle für das Immunsystem. Verschiedene Schutzsysteme wahren ihre Integrität. Sie werden als „Funktionelles Feld“ beschrieben. Sich dieses Feld anzuschauen, kann die Diagnostik von verschiedenen Erkrankungen unterstützen, darunter chronisch-entzündliche Darmerkrankungen oder Allergien. Ebenfalls können auf diese Weise Bakterien aufgespürt werden, die Krankheitsprozesse bei Typ-2-Diabetes oder Gefäßerkrankungen anfeuern.
Abundant diet components are unexplored as vital factors in intestinal homeostasis. Dietary irritants stimulate the nervous system and provoke somatosensory responses, further inducing diarrhea, gut microbiota disorder, intestinal barrier damage or even severe gastrointestinal disease. We depicted the effects of food with piquancy, high fat, low pH, high-refined carbohydrates, and indigestible texture. The mechanism of dietary irritants on intestinal homeostasis were comprehensively summarized. Somatosensory responses to dietary irritants are palpable and have specific chemical and neural mechanisms. In contrast, even low-dose exposure to dietary irritants can involve multiple intestinal barriers. Their mechanisms in intestinal homeostasis are often overlapping and dose-dependent. Therefore, treating symptoms caused by dietary irritants requires personalized nutritional advice. The reprocessing of stimulant foods, additional supplementation with probiotics or prebiotics, and enhancement of the intestinal barrier are effective intervention strategies. This review provides promising preliminary guidelines for the treatment of symptoms and gastrointestinal injury caused by dietary irritants.
The interaction between diet, microbiome, and noncommunicable disease onset is gaining growing attention. The trimethylamine N-oxide (TMAO) is a gut microbiota derivative that has been suggested as a potential regulator of human health, especially (but not exclusively) for its association with cardiovascular diseases. It derives from the trimethylamine (TMA), which is produced by the gut microbiome from dietary precursors, such as choline, betaine, and L-carnitine. Due to the potentially harmful effects of TMAO, strategies aimed to reduce circulating TMAO levels (ranging from dietary restrictions or supplementation to pharmacological treatments) have been proposed. Moreover, TMAO has been suggested as a biomarker of disease onset and prognosis. Nevertheless, contrasting evidence can be found in the literature, and mechanistic explanations or causal demonstrations of the association between the TMA/TMAO metabolism and diseases are still missing. Thus, despite promising findings, the history of TMAO might be more complex than initially hypothesized, and further studies are necessary to promote their translation into clinical practice.
As we continue to elucidate the mechanisms underlying age-related brain diseases, the reductionist strategy in nutrition-brain function research has focused on establishing the impact of individual foods. However, the biological processes connecting diet and cognition are complex. Therefore, consideration of a combination of nutritional compounds may be most efficacious. One barrier to establishing the efficacy of multi-nutrient interventions is that the area lacks an established set of evidence-based guidelines for studying their effect on brain health. This review is an output of the International Life Sciences Institute (ILSI) Europe. A multidisciplinary expert group was assembled with the aim of developing a set of considerations to guide research into the effects of multi-nutrient combinations on brain functions. Consensus recommendations converged on six key issues that should be considered to advance research in this area: 1. Establish working mechanisms of the combination and contributions of each individual compound. 2. Validate the relevance of the mechanisms for the targeted human condition. 3. Include current nutrient status, intake, or dietary pattern as inclusion/exclusion criteria in the study design. 4. Select a participant population that is clinically and biologically appropriate for all nutritional components of the combination. 5. Consider a range of cognitive outcomes. 6. Consider the limits of reductionism and the ‘gold standard’ Randomised Controlled Trial. These guiding principles will enhance our understanding of the interactive/complementary activities of dietary components, thereby strengthening the evidence-base for recommendations aimed at delaying cognitive decline.
The gut microbiota and its metabolites have become a hotspot of recent research. Trimethylamine N-oxide (TMAO) metabolized by the gut microbiota is closely related to many diseases such as cardiovascular disease, chronic kidney disease, type 2 diabetes, etc. Chronic kidney disease (CKD) is an important contributor to morbidity and mortality from non-communicable diseases. Recently, increasing focus has been put on the role of TMAO in the development and progress of chronic kidney disease. The level of TMAO in patients with chronic kidney disease is significantly increased, and a high level of TMAO deteriorates chronic kidney disease. This article describes the relationship between TMAO and chronic kidney disease and the research progress of drugs targeted TMAO, providing a reference for the development of anti-chronic kidney disease drugs targeted TMAO.
Background
Recent studies have shown that plasma trimethylamine-N-oxide (TMAO) level is highly correlated with the risk of atherosclerosis (AS), and the elevated level is significantly positively correlated with the incidence of AS.
Purpose
The purpose of this article is to offer a useful summary of the correlation between TMAO and AS, and the effect of herbal monomers, herbal extracts, and formulas on anti-atherosclerosis mediated by TMAO.
Method
The data contained in this article comes from PubMed, Web of Science, and China National Knowledge Infrastructure.
Results
This review discusses the main mechanism of AS induced by TMAO, including endothelial dysfunction, macrophage foaming, platelet reactivity, and cholesterol metabolism, and summarizes 6 herb monomers, 5 herb extracts, and 2 formulas that have been tested for their anti-TMAO activity.
Conclusion
The current understanding of possible ways to reduce TMAO generation is discussed, with the effect and potential of herb monomers, herb extracts, and formulas highlighted.
The incidence of stress-related type 2 diabetes (stress-T2D), which is aggravated by physiological stress, is increasing annually. The effects of Lactobacillus, a key component of probiotics, have been widely studied in diabetes; however, studies on the effects of postbiotics are still limited. This study aimed to examine the mechanism through which heat-killed Lactiplantibacillus plantarum LRCC5314 (HK-LRCC5314) alleviates stress-T2D in a cold-induced stress-T2D C57BL/6 mouse model. HK-LRCC5314 markedly decreased body weight gain, adipose tissue (neck, subcutaneous, and epididymal) weight, and fasting glucose levels. In the adipose tissue, mRNA expression levels of stress-T2D associated factors (NPY, Y2R, GLUT4, adiponectin, and leptin) and pro-inflammatory factors (TNF-α, IL-6, and CCL-2) were also altered. Furthermore, HK-LRCC5314 increased the abundance of Barnesiella, Alistipes, and butyrate-producing bacteria, including Akkermansia, in faeces and decreased the abundance of Ruminococcus, Dorea, and Clostridium. Thus, these findings suggest that HK-LRCC5314 exerts protective effects against stress-T2D via gut microbiome modulation, suggesting its potential as a supplement for managing stress-T2D.
Atherosclerosis is the leading cause of cardiovascular diseases worldwide. Trimethylamine N-oxide (TMAO), a metabolite of intestinal flora from dietary quaternary amines, has been shown to be closely related to the development of atherosclerosis. Previous studies have shown that Enterobacter aerogenes ZDY01 significantly reduces the serum levels of TMAO and cecal trimethylamine (TMA) in Balb/c mice; however, its role in the inhibition of choline-induced atherosclerosis in ApoE-/- mice remains unclear. Here, we demonstrated that E. aerogenes ZDY01 inhibited choline-induced atherosclerosis in ApoE-/- mice fed with 1.3% choline by reducing cecal TMA and modulating CDCA-FXR/FGF15 axis. We observed that E. aerogenes ZDY01 decreased the cecal TMA and serum TMAO levels by utilizing cecal TMA as a nutrient, not by changing the expression of hepatic FMO3 and the composition of gut microbiota. Furthermore, E. aerogenes ZDY01 enhanced the expression of bile acid transporters and reduced the cecal CDCA levels, thereby attenuating the FXR/FGF15 pathway, upregulating the expression of Cyp7a1, promoting reverse cholesterol transport. Taken together, E. aerogenes ZDY01 attenuated choline-induced atherosclerosis in ApoE-/- mice by decreasing cecal TMA and promoting reverse cholesterol transport, implying that E. aerogenes ZDY01 treatment might have therapeutic potential in atherosclerosis.
Over the past decade, changes in the composition and metabolism of gut microbiota have been linked to the development and progression of cardiovascular disease (CVD), such as atherosclerosis, hypertension (HTN), heart failure (HF), obesity, and insulin resistance. Even though the alteration in the composition of gut microbiota can be assessed by sequencing methods, there are still limited data on the inter- and intrapersonal variations in gut microbial composition in humans. Recent research has begun focusing more on the measurement of gut microbiota-related metabolites contributing to the susceptibility to cardiometabolic diseases in order to find the interactions among diet, gut microbiota, and CVD. Several gut microbial metabolites, most notably trimethylamine N-oxide, have been strongly linked to the pathogenesis of CVD. This chapter reviews the complex host-microbiota relationship, including the physiology of gut microbiota, associations between altered gut microbial composition and metabolism and CVD, and the possibility of targeting gut microbiota for developing novel treatments of CVD.
Chronic kidney disease (CKD) is characterized by the retention of a myriad of solutes termed uraemic (or uremic) toxins, which inflict damage to several organs, including the cardiovascular system. Uraemic toxins can induce hallmarks of cardiovascular disease (CVD), such as atherothrombosis, heart failure, dysrhythmias, vessel calcification and dysregulated angiogenesis. CVD is an important driver of mortality in patients with CKD; however, reliance on conventional approaches to managing CVD risk is insufficient in these patients, underscoring a need to target risk factors that are specific to CKD. Mounting evidence suggests that targeting uraemic toxins and/or pathways induced by uraemic toxins, including tryptophan metabolites and trimethylamine N-oxide (TMAO), can lower the risk of CVD in patients with CKD. Although tangible therapies resulting from our growing knowledge of uraemic toxicity are yet to materialize, a number of pharmacological and non-pharmacological approaches have the potential to abrogate the effects of uraemic toxins, for example, by decreasing the production of uraemic toxins, by modifying metabolic pathways induced by uraemic toxins such as those controlled by aryl hydrocarbon receptor signalling and by augmenting the clearance of uraemic toxins.
Trimethylamine-N-oxide (TMAO) has been reported as a risk factor for atherosclerosis development, as well as for other cardiovascular disease (CVD) pathologies. The objective of this review is to provide a useful summary on the use of phytochemicals as TMAO-reducing agents. This review discusses the main mechanisms by which TMAO promotes CVD, including the modulation of lipid and bile acid metabolism, and the promotion of endothelial dysfunction and oxidative stress. Current knowledge on the available strategies to reduce TMAO formation are discussed, highlighting the effect and potential of phytochemicals. Overall, phytochemicals (i.e., phenolic compounds or glucosinolates) reduce TMAO formation by modulating gut microbiota composition and/or function, inhibiting host's capacity to metabolize TMA to TMAO, or a combination of both. Perspectives for design of future studies involving phytochemicals as TMAO-reducing agents are discussed. Overall, the information provided by this review outlines the current state of the art of the role of phytochemicals as TMAO reducing agents, providing valuable insight to further advance in this field of study.
The observation that unhealthy diets (those that are low in whole grains, fruits and vegetables, and high in sugar, salt, saturated fat and ultra-processed foods) are a major risk factor for poor health outcomes has boosted interest in the concept of 'food as medicine'. This concept is especially relevant to metabolic diseases, such as chronic kidney disease (CKD), in which dietary approaches are already used to ameliorate metabolic and nutritional complications. Increased awareness that toxic uraemic metabolites originate not only from intermediary metabolism but also from gut microbial metabolism, which is directly influenced by diet, has fuelled interest in the potential of 'food as medicine' approaches in CKD beyond the current strategies of protein, sodium and phosphate restriction. Bioactive nutrients can alter the composition and metabolism of the microbiota, act as modulators of transcription factors involved in inflammation and oxidative stress, mitigate mitochondrial dysfunction, act as senolytics and impact the epigenome by altering one-carbon metabolism. As gut dysbiosis, inflammation, oxidative stress, mitochondrial dysfunction, premature ageing and epigenetic changes are common features of CKD, these findings suggest that tailored, healthy diets that include bioactive nutrients as part of the foodome could potentially be used to prevent and treat CKD and its complications.
There is a growing body of clinical evidence that supports a strong association between elevated circulating trimethylamine N-oxide (TMAO) levels with increased risk of developing adverse cardiovascular outcomes such as atherosclerosis and thrombosis. TMAO is synthesized through a meta-organismal stepwise process that involves (i) the microbial production of TMA in the gut from dietary precursors and (ii) its subsequent oxidation to TMAO by flavin-containing monooxygenases in the liver. Choline, L-carnitine, betaine, and other TMA-containing compounds are the major dietary precursors of TMA. TMAO can also be absorbed directly from the gastrointestinal tract after the intake of TMAO-rich foods such as fish and shellfish. Thus, diet is an important factor as it provides the nutritional precursors to eventually produce TMAO. A number of studies have attempted to associate circulating TMAO levels with the consumption of diets rich in these foods. On the other hand, there is growing interest for the development of novel food ingredients that reduce either the TMAO-induced damage or the endogenous TMAO levels through the interference with microbiota and host metabolic processes involved in TMAO pathway. Such novel functional food ingredients would offer great opportunities to control circulating TMAO levels or its effects, and potentially contribute to decrease cardiovascular risk. In this review we summarize and discuss current data regarding the effects of TMA precursors-enriched foods or diets on circulating TMAO levels, and recent findings regarding the circulating TMAO-lowering effects of specific foods, food constituents and phytochemicals found in herbs, individually or in extracts, and their potential beneficial effect for cardiovascular health.
The intestinal microbiome plays an important role in the pathogenesis of liver diseases. Alcohol intake induces gut microbiota dysbiosis and alters its function. This study investigated the antibiotic effect of allicin in mice with hepatic steatosis. Male C57BL/6 mice were administered an ethanol diet supplemented with allicin (5 and 20 mg/kg bw/day) for 4 weeks. Allicin modified the gut microbiota composition. Cecal microbiota exhibited a positive correlation with alcohol and hepatic triacylglycerol, but were suppressed with allicin. Ethanol diet with 5 mg allicin induced a lower intestinal permeability compared to ethanol diet alone. Allicin mediated the LPS-CD14-TLR4-induced hepatic inflammation pathway by reducing LPS, CD14, TLR4, and pro-inflammatory cytokines—TNF-ɑ, IL-1β, and IL-6. However, hepatic inflammation primarily resulted from alcohol toxicity rather than LPS production in the gut. The prediction of functional profiles from metagenomic 16S rRNA data revealed different functional profiles in each group. The predicted aldehyde dehydrogenase tended to increase in alcoholic mice administered allicin. The predicted LPS-related pathway and LPS biosynthesis protein results exhibited a similar trend as plasma LPS levels. Thus, alcohol and allicin intake shapes the gut microbiota and its functional profile and improves the CD14-TLR4 pathway to alleviate inflammation in the liver.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Our understanding of how diet affects health is limited to 150 key nutritional components that are tracked and catalogued by the United States Department of Agriculture and other national databases. Although this knowledge has been transformative for health sciences, helping unveil the role of calories, sugar, fat, vitamins and other nutritional factors in the emergence of common diseases, these nutritional components represent only a small fraction of the more than 26,000 distinct, definable biochemicals present in our food—many of which have documented effects on health but remain unquantified in any systematic fashion across different individual foods. Using new advances such as machine learning, a high-resolution library of these biochemicals could enable the systematic study of the full biochemical spectrum of our diets, opening new avenues for understanding the composition of what we eat, and how it affects health and disease.
Cardiovascular disease (CVD) is a leading cause of deaths and is a growing epidemic worldwide. Atherosclerosis, the primary cause of heart diseases and stroke, is associated with vascular inflammation and accumulation of lipids and fibrous elements in the arteries. Recently, blood trimethylamine-N-oxide (TMAO) has been identified as an independent risk factor for CVD in humans. TMAO is mainly derived from dietary trimethylamine (TMA)-containing nutrients via the bioconversion of gut microbiota and hepatic flavin monooxygenases (FMOs). Both in vivo and in vitro studies have revealed that TMAO promotes atherogenesis by exacerbating vascular inflammation, impairing vascular functions and disturbing cholesterol homeostasis at multiple levels. This review summarizes the current research on the microbiota-dependent generation pathway of TMAO, the associations of TMAO with atherosclerosis, and the potential dietary interventions to reduce the TMAO-associated risk of CVD.
Trimethylamine-N-oxide (TMAO) has been described as a new biomarker of cardiovascular disease (CVD), deriving from dietary choline and L-carnitine gut microbial biotransformation into trimethylamine (TMA), and subsequent hepatic oxidation. (Poly)phenols are among the dietary factors able to interfere with microbial enzymatic activity, possibly modulating TMA biotransformation at gut level. The aim of this work was investigating the in vitro biotransformation of choline and carnitine using faecal starters obtained from omnivorous and vegetarian subjects and the effect of (poly)phenol-rich foods on TMA production. Choline and L-carnitine were fermented with vegetarian or omnivorous faecal slurries, alone or in combination with 10 (poly)phenol-rich food items. TMA production from carnitine, but not from choline, was significantly lower when vegetarian faecal starters were used, and, among the tested food items, blonde orange juice significantly reduced TMA formation during faecal biotransformation. Consequently, the main compounds of orange juice, namely phenolic compounds, terpenes, limonoids, organic acids and sugars, were tested individually. Sugars exerted the highest inhibitory effect on TMA production. Despite some limitations deriving from the applied in vitro model, this is the first work describing a possible role of some (poly)phenol-rich dietary products on the modulation of TMA colonic production. Free sugars were the main responsible of TMA inhibition, suggesting a potential beneficial role of colonic fermentation of carbohydrates in reducing TMA formation from its precursor molecules. This work opens new research lines to evaluate the effect of the dietary fermentable fibre in TMA production and, potentially, on circulating TMAO levels.
Objective
The gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance.
Design
A pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation.
Results
The OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal CntA gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT.
Conclusion
The OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment.
Trial registration number
NCT02838732 ; Results.
Subway systems are indispensable for urban societies, but microbiological characteristics of subway aerosols are relatively unknown. Previous studies investigating microbial compositions in subways employed methodologies that underestimated the diversity of microbial exposure for commuters, with little focus on factors governing subway air microbiology, which may have public health implications. Here, a culture-independent approach unraveling the bacterial diversity within the urban subway network in Hong Kong is presented. Aerosol samples from multiple subway lines and outdoor locations were collected. Targeting the 16S rRNA gene V4 region, extensive taxonomic diversity was found, with the most common bacterial genera in the subway environment among those associated with skin. Overall, subway lines harbored different phylogenetic communities based on α- and β-diversity comparisons, and closer inspection suggests that each community within a line is dependent on architectural characteristics, nearby outdoor microbiomes, and connectedness with other lines. Microbial diversities and assemblages also varied depending on the day sampled, as well as the time of day, and changes in microbial communities between peak and nonpeak commuting hours were attributed largely to increases in skin-associated genera in peak samples. Microbial diversities within the subway were influenced by temperature and relative humidity, while carbon dioxide levels showed a positive correlation with abundances of commuter-associated genera. This Hong Kong data set and communities from previous studies conducted in the United States formed distinct community clusters, indicating that additional work is required to unravel the mechanisms that shape subway microbiomes around the globe.
Gut microbiota is found in virtually any metazoan, from invertebrates to vertebrates. It has long been believed that gut microbiota, more specifically, the activity of the microbiome and its metabolic products, directly influence a variety of aspects in metazoan physiology. However, the exact molecular relationship among microbe-derived gut metabolites, host signaling pathways, and host physiology remains to be elucidated. Here we review recent discoveries regarding the molecular links between gut metabolites and host physiology in different invertebrate and vertebrate animal models. We describe the different roles of gut microbiome activity and their metabolites in regulating distinct host physiology and the molecular mechanisms by which gut metabolites cause physiological homeostasis via regulating specific host signaling pathways. Future studies in this direction using different animal models will provide the key concepts to understanding the evolutionarily conserved chemical dialogues between gut microbiota and metazoan cells and also human diseases associated with gut microbiota and metabolites.
Epidemiological evidences throughout the years have indicated that consumption of phytochemicals may play important functions in the regulation of pathological and normal biological processes. Polyphenols are one of the large and ubiquitous groups of phytochemicals. Dietary polyphenols are naturally present in a wide variety of fruits and vegetables, and potentially contribute to the maintenance of human health. However, growing information has indicated that the bioactive compounds from polyphenols may exert beneficial effects in part by their metabolites. The bioactive metabolites were converted by the gut microflora, liver microsomes and hepatocytes, and identified in intestinal, plasma, feces, and urine after dietary ingestion. Surprisingly, recent studies suggested that many metabolites possess more active biological functions than their precursors. In order to explore the possibilities of metabolites in food bioactive compounds, more clear understanding of the metabolic pathways and the molecular targets responsible for health promotion and diseases prevention are needed. In this review, we first summarize the distribution and beneficial health activities of metabolites from dietary polyphenols. We also discuss the available evidence on the relationship between metabolites bioefficacy and bioavailability of their parent polyphenol compounds. We hope that this knowledge will lead to future research to discover and develop new bioactive compounds as possible chemopreventive agents.
Significance
Metabolism of l -carnitine, a compound abundant in human diet, to trimethylamine by human microbiota has been shown to promote atherosclerosis and subsequent development of heart disease. However, the underpinning molecular and biochemical mechanisms remain unknown. In this study, we reveal that a previously unidentified Rieske-type protein is responsible for carnitine transformation to trimethylamine from human microbiota. Knowledge gained in our study provides the opportunity not only to explore Rieske protein inhibitors in preventing trimethylamine formation in animal studies and clinical trials, but also for its use as a functional genetic marker to better understand human microbiota and their dynamics in our health and disease in future epidemiological studies and dietary interventions.
Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
Recent studies in animals have shown a mechanistic link between intestinal microbial metabolism of the choline moiety in dietary phosphatidylcholine (lecithin) and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO). We investigated the relationship among intestinal microbiota-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and adverse cardiovascular events in humans.
We quantified plasma and urinary levels of TMAO and plasma choline and betaine levels by means of liquid chromatography and online tandem mass spectrometry after a phosphatidylcholine challenge (ingestion of two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine) in healthy participants before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics. We further examined the relationship between fasting plasma levels of TMAO and incident major adverse cardiovascular events (death, myocardial infarction, or stroke) during 3 years of follow-up in 4007 patients undergoing elective coronary angiography.
Time-dependent increases in levels of both TMAO and its d9 isotopologue, as well as other choline metabolites, were detected after the phosphatidylcholine challenge. Plasma levels of TMAO were markedly suppressed after the administration of antibiotics and then reappeared after withdrawal of antibiotics. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event (hazard ratio for highest vs. lowest TMAO quartile, 2.54; 95% confidence interval, 1.96 to 3.28; P<0.001). An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors (P<0.001), as well as in lower-risk subgroups.
The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota. Increased TMAO levels are associated with an increased risk of incident major adverse cardiovascular events. (Funded by the National Institutes of Health and others.).
Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary l-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of l-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma l-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary l-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.
Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.
Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine--choline, trimethylamine N-oxide (TMAO) and betaine--were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
During recent years, the composition of the gut microbiota (GM) has received increasing attention as a factor in the development of experimental inflammatory disease in animal models. Because increased variation in the GM might lead to increased variation in disease parameters, determining and reducing GM variation between laboratory animals may provide more consistent models. Both genetic and environmental aspects influence the composition of the GM and may vary between laboratory animal breeding centers and within an individual breeding center. This study investigated the variation in cecal microbiota in 8-wk-old NMRI and C57BL/6 mice by using denaturing gradient gel electrophoresis to profile PCR-derived amplicons from bacterial 16S rRNA genes. Comparison of the cecal microbiotas revealed that the similarity index of the inbred C57BL/6Sca strain was 10% higher than that of the outbred Sca:NMRI stock. Comparing C57BL/6 mice from 2 vendors revealed significant differences in the microbial profile, whereas the profiles of C57BL/6Sca mice raised in separate rooms within the same breeding center were not significantly different. Furthermore, housing in individually ventilated cages did not lead to intercage variation. These results show that denaturing gradient gel electrophoresis is a simple tool that can be used to characterize the gut microbiota of mice. Including such characterizations in future quality-control programs may increase the reproducibility of mouse studies.
Chronic Helicobacter pylori disease is reduced withAllium vegetable intake. This study was designed to assess the in vivo anti-H. pylori potential of a variety of garlic substances. The garlic materials all showed substantial but widely differing anti-H. pylori effects against all strains and isolates tested. The MICs (range, 8 to 32 μg/ml) and minimum bactericidal concentrations
(MBCs) (range, 16 to 32 μg/ml) of undiluted garlic oil (GO) were smaller than those of garlic powder (GP) (MIC range, 250
to 500 μg/ml; MBC range, 250 to 500 μg/ml) but greater than the MIC of allicin (4.0 μg/ml) (Table 2) present in GP. Allicin (MIC, 6 μg/ml; MBC, 6 μg/ml) was more potent than diallyl disulfide (MIC range, 100 to 200 μg/ml;
MBC range, 100 to 200 μg/ml), its corresponding sulfide, but of a strength similar to that of diallyl tetrasulfide (MIC range,
3 to 6 μg/ml; MBC range, 3 to 6 μg/ml). Antimicrobial activity of the diallyl sulfides increased with the number of sulfur
atoms. Time course viability studies and microscopy showed dose-dependent anti-H. pylori effects with undiluted GO, GP, allicin, and diallyl trisulfide after a lag phase of ca. 1 to 2 h. Substantial in vitro anti-H. pylori effects of pure GO and GP and their diallyl sulfur components exist, suggesting their potential for in vivo clinical use
against H. pylori infections.
Although garlic has been used for its medicinal properties for thousands of years, investigations into its mode of action are relatively recent. Garlic has a wide spectrum of actions; not only is it antibacterial, antiviral, antifungal and antiprotozoal, but it also has beneficial effects on the cardiovascular and immune systems. Resurgence in the use of natural herbal alternatives has brought the use of medicinal plants to the forefront of pharmacological investigations, and many new drugs are being discovered. This review aims to address the historical use of garlic and its sulfur chemistry, and to provide a basis for further research into its antimicrobial properties.
As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.
The authors recently described a potential role of the phosphatidylcholine metabolic pathway involving gut flora in contributing to the pathogenesis of atherosclerotic coronary disease in an animal model (Wang Z et al, Nature 2011;472:57-63). TMAO is an intestinal flora-dependent metabolite of the choline group of phosphatidylcholine that is excreted in the urine (Simenhoff ML et al, Lancet 1976;2:818-21). The major dietary source of choline is lecithin, a part of the B-complex vitamin family. Choline and its metabolites, such as betaine, can serve as a source of the methyl groups required for proper metabolism of amino acids such as homocysteine and methionine (Zeisel AQ et al, Annu Rev Nutr 2006;26:229-50). Diets rich in phosphatidylcholine (those containing eggs, liver, beef, and pork) can contribute to the formation of the metabolite trimethylamine, with conversion to TMAO. TMAO production may be facilitated by intestinal microflora, thereby, potentially, providing a link between atherogenic diets, intestinal microflora, and atherosclerotic disease. The authors investigated the relationship of intestinal microflora-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and cardiovascular events in humans. Plasma and urinary levels of TMAO and plasma choline and betaine levels were measured with liquid chromatography and gas spectrometry after a phosphatidylcholine challenge (two hard-boiled eggs with deuterium [d9]-labeled phosphatidylcholine) in healthy participants before and after suppression of intestinal microbiota with oral broad-spectrum antibiotics. Fasting plasma levels of TMAO were also examined in conjunction with incident major adverse cardiovascular events (death, myocardial infarction, or stroke) during 3 years of follow-up in 4007 patients undergoing elective coronary angiography. The authors found time-dependent increases in levels of TMAO and its [d9] isotopologue, as well as other choline metabolites, after the phosphatidylcholine challenge. TMAO plasma levels were suppressed after administration of antibiotics and reappeared after withdrawal of antibiotics. Increased plasma levels of TMAO were associated with an increased risk of major adverse cardiovascular events (hazard ratio for highest vs lowest TMAO quartile, 2.54; 95% confidence interval, 1.96-3.28; P < .001). After adjustment for traditional cardiovascular risk factors, an elevated TMAO level predicted an increased risk of major cardiovascular events (P < .001).
Tea is one of the most widely consumed beverages worldwide and has received increasing attention from researchers and food industries for various reasons mainly related to its health benefits. Polyphenols, such as catechins for green tea and theaflavins and thearubigins for black tea, are considered to be the main active components of tea. Recently, there is increasing awareness that the beneficial health effects of tea could be partly contributed by breakdown products of its polyphenols formed in the gut. Different studies have been carried out to understand the formation of microbially derived metabolites of tea components and their bioactivities. In general, tea catechins are typically transformed to specific hydroxyphenyl-γ-valerolactones, which could be further metabolized to smaller phenolic acids by gut flora. This review summarizes the current knowledge on the metabolism of major tea components by gut microbiota and the bioactivities of their metabolites.
Fatty liver is significantly associated with hepatic cirrhosis and liver cancer. Excessive alcohol consumption causes alcoholic fatty liver disease (AFLD). Ginger has been reported to exhibit antioxidant potential and hepatoprotective activity. In the present study, a mouse model for AFLD was developed by employing male C57BL/6 mice who were fed an alcohol-containing liquid diet (Lieber-DeCarli diet) ad libitum. In the treatment groups, ginger essential oil (GEO) and citral were orally administered every day for 4 weeks. Serum biochemical analysis, antioxidant enzyme activity analysis, and histopathological evaluation revealed that GEO and citral exhibited hepatoprotective activity against AFLD. Metabolites in serum samples were profiled by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS). Metabolomic data indicated the amounts of metabolites such as D-glucurono-6,3-lactone, glycerol-3-phosphate, pyruvic acid, lithocholic acid, 2-pyrocatechuic acid, and prostaglandin E1 were increased after alcohol administration, but the levels were recovered in treatment groups. Our analysis indicated that ginger possesses hepatoprotective properties against AFLD. Further, these metabolites can serve as early non-invasive candidate biomarkers in the clinical application of AFLD for health management.
Diet is a major factor driving the composition and metabolism of the colonic microbiota. The amount, type and balance of the main dietary macronutrients (carbohydrates, proteins and fats) have a great impact on the large intestinal microbiota. The human colon contains a dense population of bacterial cells that outnumber host cells 10-fold. Bacteroidetes, Firmicutes and Actinobacteria are the three major phyla that inhabit the human large intestine and these bacteria possess a fascinating array of enzymes that can degrade complex dietary substrates. Certain colonic bacteria are able to metabolise a remarkable variety of substrates whilst other species carry out more specialised activities, including primary degradation of plant cell walls. Microbial metabolism of dietary carbohydrates results mainly in the formation of short chain fatty acids and gases. The major bacterial fermentation products are acetate, propionate and butyrate; and the production of these tends to lower the colonic pH. These weak acids influence the microbial composition and directly affect host health, with butyrate the preferred energy source for the colonocytes. Certain bacterial species in the colon survive by cross-feeding, using either the breakdown products of complex carbohydrate degradation or fermentation products such as lactic acid for growth. Microbial protein metabolism results in additional fermentation products, some of which are potentially harmful to host health. The current 'omic era promises rapid progress towards understanding how diet can be used to modulate the composition and metabolism of the gut microbiota, allowing researchers to provide informed advice, that should improve long-term health status.
The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease.
Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. This goal is formidable. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time - especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.
Garlic has been used throughout history for both culinary and medicinal purpose. Allicin is a major component of crushed garlic. Although it is sensitive to heat and light and easily metabolized into various compounds such as diallyl disulfide, diallyl trisulfide, and diallyl sulfide, allicin is still a major bioactive compound of crushed garlic. The mortality of hepatocellular carcinoma is quite high and ranks among the top 10 cancer-related deaths in Taiwan. Although numerous studies have shown the cancer-preventive properties of garlic and its components, there is no study on the effect of allicin on the growth of human liver cancer cells. In this study, we focused on allicin-induced autophagic cell death in human liver cancer Hep G2 cells. Our results indicated that allicin induced p53-mediated autophagy and inhibited the viability of human hepatocellular carcinoma cell lines. Using Western blotting, we observed that allicin decreased the level of cytoplasmic p53, the PI3K/mTOR signaling pathway, and the level of Bcl-2 and increased the expression of AMPK/TSC2 and Beclin-1 signaling pathways in Hep G2 cells. In addition, the colocalization of LC3-II with MitoTracker-Red (labeling mitochondria), resulting in allicin-induced degradation of mitochondria, could be observed by confocal laser microscopy. In conclusion, allicin of garlic shows great potential as a novel chemopreventive agent for the prevention of liver cancer.
The in vitro antibacterial activity of essential oils (EOs) obtained from fresh bulbs of garlic, Allium sativum L., and leek, Allium porrum L. ( Alliaceae), was studied. A. sativum (garlic) EO showed a good antimicrobial activity against Staphylococcus aureus (inhibition zone 14.8 mm), Pseudomonas aeruginosa (inhibition zone 21.1 mm), and Escherichia coli (inhibition zone 11.0 mm), whereas the EO of A. porrum (leek) had no antimicrobial activity. The main constituents of the garlic EO were diallyl monosulfide, diallyl disulfide (DADS), diallyl trisulfide, and diallyl tetrasulfide. The EO of A. porrum was characterized by the presence of dipropyl disulfide (DPDS), dipropyl trisulfide, and dipropyl tetrasulfide. The antimicrobial activities of the DADS and DPDS were also studied. The results obtained suggest that the presence of the allyl group is fundamental for the antimicrobial activity of these sulfide derivatives when they are present in Allium or in other species (DADS inhibition zone on S. aureus 15.9 mm, P. aeruginosa 21.9 mm, E. coli 11.4 mm). Copyright © 2012 John Wiley & Sons, Ltd.
Meat consumption is inconsistently associated with development of coronary heart disease (CHD), stroke, and diabetes mellitus, limiting quantitative recommendations for consumption levels. Effects of meat intake on these different outcomes, as well as of red versus processed meat, may also vary.
We performed a systematic review and meta-analysis of evidence for relationships of red (unprocessed), processed, and total meat consumption with incident CHD, stroke, and diabetes mellitus. We searched for any cohort study, case-control study, or randomized trial that assessed these exposures and outcomes in generally healthy adults. Of 1598 identified abstracts, 20 studies met inclusion criteria, including 17 prospective cohorts and 3 case-control studies. All data were abstracted independently in duplicate. Random-effects generalized least squares models for trend estimation were used to derive pooled dose-response estimates. The 20 studies included 1 218 380 individuals and 23 889 CHD, 2280 stroke, and 10 797 diabetes mellitus cases. Red meat intake was not associated with CHD (n=4 studies; relative risk per 100-g serving per day=1.00; 95% confidence interval, 0.81 to 1.23; P for heterogeneity=0.36) or diabetes mellitus (n=5; relative risk=1.16; 95% confidence interval, 0.92 to 1.46; P=0.25). Conversely, processed meat intake was associated with 42% higher risk of CHD (n=5; relative risk per 50-g serving per day=1.42; 95% confidence interval, 1.07 to 1.89; P=0.04) and 19% higher risk of diabetes mellitus (n=7; relative risk=1.19; 95% confidence interval, 1.11 to 1.27; P<0.001). Associations were intermediate for total meat intake. Consumption of red and processed meat were not associated with stroke, but only 3 studies evaluated these relationships.
Consumption of processed meats, but not red meats, is associated with higher incidence of CHD and diabetes mellitus. These results highlight the need for better understanding of potential mechanisms of effects and for particular focus on processed meats for dietary and policy recommendations.
Ajoene, a garlic-derived sulfur-containing compound that prevents platelet aggregation, exhibited broad-spectrum antimicrobial activity. Growth of gram-positive bacteria, such as Bacillus cereus, Bacillus subtilis, Mycobacterium smegmatis, and Streptomyces griseus, was inhibited at 5 micrograms of ajoene per ml. Staphylococcus aureus and Lactobacillus plantarum also were inhibited below 20 micrograms of ajoene per ml. For gram-negative bacteria, such as Escherichia coli, Klebsiella pneumoniae, and Xanthomonas maltophilia, MICs were between 100 and 160 micrograms/ml. Ajoene also inhibited yeast growth at concentrations below 20 micrograms/ml. The microbicidal effect of ajoene on growing cells was observed at slightly higher concentrations than the corresponding MICs. B. cereus and Saccharomyces cerevisiae were killed at 30 micrograms of ajoene per ml after 24 h of cultivation when cultivation was started at 10(5) cells per ml. However, the minimal microbicidal concentrations for resting cells were at 10 to 100 times higher concentrations than the corresponding MICs. The disulfide bond in ajoene appears to be necessary for the antimicrobial activity of ajoene, since reduction by cysteine, which reacts with disulfide bonds, abolished its antimicrobial activity.
Allicin, one of the active principles of freshly crushed garlic homogenates, has a variety of antimicrobial activities. Allicin in its pure form was found to exhibit i) antibacterial activity against a wide range of Gram-negative and Gram-positive bacteria, including multidrug-resistant enterotoxicogenic strains of Escherichia coli; ii) antifungal activity, particularly against Candida albicans; iii) antiparasitic activity, including some major human intestinal protozoan parasites such as Entamoeba histolytica and Giardia lamblia; and iv) antiviral activity. The main antimicrobial effect of allicin is due to its chemical reaction with thiol groups of various enzymes, e.g. alcohol dehydrogenase, thioredoxin reductase, and RNA polymerase, which can affect essential metabolism of cysteine proteinase activity involved in the virulence of E. histolytica.
Six different mixtures of garlic distilled oils containing diallyl disulfide (DDS) and diallyl trisulfide (DTS), ranging from 1 to 51% and 88 to 38% respectively, have been assayed against a number of yeasts (C. albicans, C. tropicalis and B. capitatus), gram-positive bacteria (S. aureus and B. subtilis) and gram-negative bacteria (P. aeruginosa and E. coli). Results obtained support a specific antifungal more than an antibacterial activity and implicate DDS as the active constituent. Incubation of garlic extracts made up of 1% DDS and 88% DTS resulted, in fact, in the absence of growth inhibition against all the tested microorganisms, whereas garlic oils with higher quantities of DDS showed significant inhibitory activity, increasing with the increase of DDS amount.
In support of a new clinical trial designed to compare the effects of crushed fresh garlic and two types of garlic supplement tablets (enteric-coated dried fresh garlic and dried aged garlic extract) on serum lipids, the three garlic products have been characterized for (a) composition (14 sulfur and 2 non-sulfur compounds), (b) stability of suspected active compounds, and (c) availability of allyl thiosulfinates (mainly allicin) under both simulated gastrointestinal (tablet dissolution) conditions and in vivo. The allyl thiosulfinates of blended fresh garlic were stable for at least 2 years when stored at -80 degrees C. The dissolution release of thiosulfinates from the enteric-coated garlic tablets was found to be >95%. The bioavailability of allyl thiosulfinates from these tablets, measured as breath allyl methyl sulfide, was found to be complete and equivalent to that of crushed fresh garlic. S-Allylcysteine was stable for 12 months at ambient temperature. The stability of the suspected active compounds under the conditions of the study and the bioavailability of allyl thiosulfinates from the dried garlic supplement have validated the use of these preparations for comparison in a clinical trial.
Many microbial genomes have been sequenced in the recent years. Multiple genes encoding Rieske iron-sulfur proteins, which are subunits of cytochrome bc-type complexes or oxygenases, have been detected in many pro- and eukaryotic genomes. The diversity of substrates, co-substrates and reactions offers obvious explanations for the diversity of the low potential Rieske proteins associated with oxygenases, but the physiological significance of the multiple genes encoding high potential Rieske proteins associated with the cytochrome bc-type complexes remains elusive. For some organisms, investigations into the function of the later group of genes have been initiated. Here, we summarize recent finding on the characteristics and physiological functions of multiple high potential Rieske proteins in prokaryotes. We suggest that the existence of multiple high potential Rieske proteins in prokaryotes could be one way of allowing an organism to adapt their electron transfer chains to changing environmental conditions.
Consideration of the underlying features responsible for garlic-allicin's antimicrobial activity as well as its instability has prompted an investigation into substituted S-aryl alkylthiolsulfinates as a class of garlic mimic with enhanced stability. Synthesis of the targets has inspired the development of new methods for synthesizing unsymmetrical aralkyl disulfides, which are then oxidized to the targets. Some simple representatives have been synthesized, setting the scene for a full SAR study of this relatively unexplored class of thiolsulfinate.
The aim of the present study was to evaluate the association between meat consumption and the prevalence of a first, non-fatal event of an acute coronary syndrome (ACS), in a Greek sample.
Randomized, case-control study.
Tertiary care.
A total of 848 out of 956 patients who had been randomly selected from hospitals with first event of an ACS and 1078 population-based controls, age and sex matched.
Detailed information regarding their medical records, alcohol intake, physical activity and smoking habits was recorded. Nutritional habits were evaluated with a semiquantitative food-frequency questionnaire. Multiple logistic regression analysis estimated the odds ratio of having ACS by level of meat intake, after taking into account several confounders.
Patients consumed higher quantities of meat compared with controls (6.5+/-2.9 vs 4.9+/-2.1 portions per month, P<0.001). Food-specific analysis showed that red meat consumption was strongly associated with 52% increased odds of ACS (95% confidence interval (CI) 1.47-1.58). On the contrary, white meat consumption seems to be associated with only 18% likelihood of having cardiac events (95% CI 1.11-1.26). Participants who consumed >8 portions red meat and >12 portions white meat per month had 4.9 times and 3.7 higher odds of having ACS, respectively (P<0.001), compared with low meat intake (<4 portions and <8 portions per month, respectively).
Increased red meat consumption showed a strong positive association with cardiac disease risk, whereas white meat consumption showed less prominent results, after controlling for several potential confounding factors.
Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
- W H Tang
- Z Wang
- B S Levison
- R A Koeth
- E B Britt
- X Fu
- Y Wu
- S L Hazen
Tang, W. H., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X.,
Wu, Y., & Hazen, S. L. (2013). Intestinal microbial metabolism
of phosphatidylcholine and cardiovascular risk. The New
England Journal of Medicine, 368, 1575-1584.