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The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the h...
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Context 1
... comprehensive map may help define the phenotype of an organism at a specific time ( Zhang et al., 2012). Therefore, the analysis of metabolic differences between unperturbed and perturbed pathways could provide insights on the underlying disease prognosis and diagnosis (Zhang et al., 2012; Figure 2). ...
Context 2
... intestinal gut dysbiosis is associated with a plethora of children and adult diseases, including genetic (i.e., cystic fibrosis [CF]), inflammatory (i.e., inflammatory bowel diseases and syndrome [IBDs, IBS], Chron's [CD], ulcerative colitis [UC], and celiac disease), metabolic (i.e., diabetes, obesity and non-alcoholic fatty liver disease [NAFLD]), and allergic (i.e., atopic dermatitis, food allergies) disorders , and neuropathologies (i.e., autism) (Figure 2). ...
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Citations
... This technology can also identify novel phage proteins and lipids. In terms of metagenomics, MS can be used to identify the proteome and lipidome of unculturable bacteria and therefore aid in the understanding of their genome (Vernocchi et al., 2016). Furthermore, it can be utilized to help examine the interactome, or the influence of the molecular interactions between phage and their host (Milewska et al., 2019). ...
... [14][15][16] Hence, metabolomics has become an increasingly promising tool for understanding the relationship between the host and gut microbiota. 17 Liquid chromatography-mass spectrometry (LC-MS) is an extremely sensitive, specific, high-resolution metabolomics research technique with high throughput, resolution, and sensitivity. A metabolic profile can be used as a diagnostic, prognostic or therapeutic biomarker in clinical medicine, providing new insight into disease pathogenesis. ...
The aim of this study was to explore the impact of chronic apical periodontitis (CAP) on atherosclerosis in apoE −/− mice fed high-fat diet (HFD). This investigation focused on the gut microbiota, metabolites, and intestinal barrier function to uncover potential links between oral health and cardiovascular disease (CVD). In this study, CAP was shown to exacerbate atherosclerosis in HFD-fed apoE −/− mice, as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining. 16S rRNA sequencing revealed significant alterations in the gut microbiota, with harmful bacterial species thriving while beneficial species declining. Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis, leading to elevated levels of taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TDCA). These metabolic shifts may contribute to atherosclerosis development. Furthermore, impaired intestinal barrier function, characterized by reduced mucin expression and disrupted tight junction proteins, was observed. The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions, highlighting the importance of the intestinal barrier in cardiovascular health. In conclusion, this research underscores the intricate interplay among oral health, gut microbiota composition, metabolite profiles, and CVD incidence. These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues, as well as the need for further investigations into the intricate mechanisms linking oral health, gut microbiota, and metabolic pathways in CVD development.
... Acetate is a crucial SCFA present in the gut, especially in the colon, with trophic effects on the colonic epithelium and mucosal blood flux (Vernocchi, Del Chierico, & Putignani, 2016), and the knowledge of the role of microbiota-derived acetate in health and disease is increasing (Antunes et al., 2019;Bhattarai et al., 2017;Chen et al., 2023;Erny et al., 2021;Jugder, Kamareddine, & Watnick, 2021;Lin et al., 2022;Marques et al., 2017;Niu et al., 2023;. The other SCFAs, propionate (Bai et al., 2021;Bajic et al., 2020;Bindels et al., 2012;Chen et al., 2021;Dürholz et al., 2022;Hou et al., 2021;Huang et al., 2020;Huang, Shi, Xu, & Ji, 2021;Kim et al., 2019;Langfeld, Du, Bereswill, & Heimesaat, 2021;Li et al., 2021;Su, Braat, & Peppelenbosch, 2021;Yan et al., 2022) and butyrate (Amiri et al., 2022;Bridgeman et al., 2020;Couto, Gonçalves, Magro, & Martel, 2020;Gheorghe et al., 2022;Stilling et al., 2016) are involved as well in important metabolic pathways and systemic conditions. ...
... Many of these micromolecules have not been extensively studied and do not fit into traditional nutrient types. Currently, the importance of micronutrients and gut microbiota-derived metabolites in health and disease has gained a high impact (Shenkin, 2006;Vernocchi et al., 2016;Liu et al., 2022), yet their responsible transporters are not well understood. Understanding the absorption and reabsorption mechanisms of dietary micronutrients and gut microbiota-derived metabolites will provide a key molecular process for controlling their dynamics and molecular activities. ...
Transporter research primarily relies on the canonical substrates of well-established transporters. This approach has limitations when studying transporters for the low-abundant micromolecules, such as micronutrients, and may not reveal physiological functions of the transporters. While d -serine, a trace enantiomer of serine in the circulation, was discovered as an emerging biomarker of kidney function, its transport mechanisms in the periphery remain unknown. Here, using a multi-hierarchical approach from body fluids to molecules, combining multi-omics, cell-free synthetic biochemistry, and ex vivo transport analyses, we have identified two types of renal d -serine transport systems. We revealed that the small amino acid transporter ASCT2 serves as a d -serine transporter previously uncharacterized in the kidney and discovered d -serine as a non-canonical substrate of the sodium-coupled monocarboxylate transporters (SMCTs). These two systems are physiologically complementary, but ASCT2 dominates the role in the pathological condition. Our findings not only shed light on renal d -serine transport, but also clarify the importance of non-canonical substrate transport. This study provides a framework for investigating multiple transport systems of various trace micromolecules under physiological conditions and in multifactorial diseases.
... Metabolites undergo analysis to profile the metabolic activity of microbial hosts. [67,69,70] DNA microarrays ...
Parkinson's disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the central nervous system. Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a growing interest concerning the role of the gut microbiome in the etiology and pathophysiology of PD. The establishment of a brain-gut microbiome axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota through metabolic, immune, neuronal, and endocrine mechanisms and pathways. Among these, the vagus nerve represents the most direct form of communication between the brain and the gut. Given the potential interactions between bacteria and drugs, it has been observed that the therapies for PD can have an impact on the composition of the microbiome. Therefore, in the scope of the present review, we will discuss the current understanding of gut microbiome on PD and whether this may be a new paradigm for treating this devastating disease.
... TLR4-MD2 is typically expressed in microglia, dendritic cells, monocytes and macrophages, and their interaction with LPS induces downstream proinflammatory cytokine production and cell proliferation [158][159][160]. Polysaccharide A is another gut gram-negative Bacteroides fragilis component that interacts with TLR and specifically trigger an inflammatory response in the CNS including microglial activation that ultimately led to neuronal loss [161,162]. Furthermore, LPS interact with lipopolysaccharide-binding protein (LBP) and brain-specific angiogenesis inhibitor 1 (BAI1) which are abundantly expressed in glial cells and neurons that induce anti-angiogenic effects in a brain tumour model [155]. LPS has been found in glioblastoma microenvironment of patient samples [163], and TLR4 highly expressed in patients' glioma cells tumour in addition to glioma stem-like cells [164]. ...
... Microbiota-produced metabolites, like short-chain fatty acids (SCFAs), have the potential to reduce inflammation. Metabolites produced by the microbiota, such as short-chain fatty acids (SCFAs), may exert anti-inflammatory effects, modulate intestinal immune activity, and enhance epithelial barrier function (Vernocchi et al., 2016;Cheng et al., 2022). Our results are consistent with a previous study (Liu et al., 2022) that showed supplementing with B. coagulans can increase levels of SCFAs. ...
Introduction
Alcoholic-associated liver diseases (ALD) are now widespread issues worldwide. Alcoholic-induced chronic dysbiosis of the gut microbiota is one of the factors in the pathophysiology of ALD.
Methods
In this work, we employed a chronic-binge ethanol feeding mice model, as described in a previous report.
Results
Our findings demonstrate that hepatic inflammatory injury damage and accumulation of fat can be effectively reduced in mice with ALD by altering the gut microbiota utilizing Bacillus coagulans. Treatment with B. coagulans significantly modulates the levels of TNF-α, IL-1β, and IL-22 cytokines while maintaining tight junction proteins and mucin protein expressions to support intestinal barrier function restoration. Treatment with B. coagulans also alters the composition of the gut microbiota and increases the production of short-chain fatty acids (SCFAs).
Discussion
This is mostly due to B. coagulans promotes the growth of bacteria that produce SCFAs, such as Ruminococcus species and Akkermansia, while inhibiting the growth of pathogenic bacteria like Escherichia Shigella. Moreover, treatment with B. coagulans causes levels of 2-Ketobutyric acid, ketoleucine, and indoleacetic acid increase while homovanillic acid and 3’-O-Methylguanosine metabolites decrease significantly. This study facilitates the development of therapeutic and preventive strategies for ALD using lactic acid bacteria.
... Indeed, it is described that IBD patients have a 25% higher production of these BCFA [102] and in vitro experiments with high concentrations of iso-valerate stimulated the release of pro-inflammatory cytokines [103] . However, not many other (in vitro) studies have been performed with these BCFA and additionally iso-butyrate is poorly metabolized by enterocytes [104,105] ; thus, the potential effect of BCFA remains rather speculative here. Likely, another metabolite, or group of metabolites, contributes to the additional positive effects of the inulintreated supernatant on intestinal barrier function and inflammation. ...
Background: The gut and its microbiome have a major impact on many aspects of health and are therefore also an attractive target for drug- or food-based therapies. Here, we report on the added value of combining a microbiome screening model, the i-screen, with fresh intestinal tissue explants in a microfluidic gut-on-a-chip model, the Intestinal Explant Barrier Chip (IEBC).
Methods: Adult human gut microbiome (fecal pool of 6 healthy donors) was cultured anaerobically in the i-screen platform for 24 h, without and with exposure to 4 mg/mL inulin. The i-screen cell-free culture supernatant was subsequently applied to the luminal side of adult human colon tissue explants (n = 3 donors), fixed in the IEBC, for 24 h and effects were evaluated.
Results: The supplementation of the media with inulin promoted the growth of Anaerostipes , Bifidobacterium , Blautia , and Collinsella in the in vitro i-screen, and triggered an elevated production of butyrate by the microbiota. Human colon tissue exposed to inulin-treated i-screen cell-free culture supernatant or control i-screen cell-free culture supernatant with added short-chain fatty acids (SCFAs) showed improved tissue barrier integrity measured by a 28.2%-34.2% reduction in FITC-dextran 4000 (FD4) leakage and 1.3 times lower transport of antipyrine. Furthermore, the release of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α was reduced under these circumstances. Gene expression profiles confirmed these findings, but showed more profound effects for inulin-treated supernatant compared to SCFA-supplemented supernatant.
Conclusion: The combination of i-screen and IEBC facilitates the study of complex intestinal processes such as host-microbial metabolite interaction and gut health.
... Understanding these changes is of paramount relevance to complete the factors influencing the success of non-typhoidal Salmonella serovars in swine salmonellosis. 7 The gut microbiota participates actively in a number of metabolic processes including vitamin and SCFA production, amino acids synthesis, bile acid biotransformation or hydrolisis and fermentation of non-digestible substrates [17]. We observed a good overlap between prediction of metabolic routes and metabolomic results in differentially abundant amino acids. ...
Salmonella Typhimurium infection in pigs is characterized by an intense inflammatory response in early infection which seems to dysregulate host physiology including the gut microbiota. Both, changes in host physiology and microbiome composition, must entail modifications within the gut environment. This study analyzes the gut metabolome in early infected pigs (48 hours after infection) and non-infected controls by untargeted metabolomics (LC–QTOF MS/MS and GC–TOF MS), supported with microbiome data (16S rRNA abundance and prediction functional analyses). The metabolomic profile in Salmonella-infected pigs differed from healthy controls in 39 of these metabolites, including eight amino acids, four bile acids and carboxylic acids, three carnitines and sugar derivates, eleven fatty acids and six other compounds. Changes in amino acids abundance and the observed decrease of proteolytic bacteria such as Lactobacillus or Bacteroides could favor the niche colonization by Desulfovibrionaceae. In addition, the decrease in short chain fatty acids and tricarboxylic acids cycle was correlated to a decrease in beneficial bacteria in infected pigs. Interestingly, we observed an increase of bile acids concentration and compounds such as succinic acid or pantothenic acid, which may boost the inflammatory response. Altogether, the results reveal how S. Typhimurium infection alters the gut microbiome composition and prompts changes in the metabolism with a potential interaction between intestinal metabolism and microbiota abundance.
... Additionally, the presence of acetone in feces has been correlated with specific gut taxa in pathologies involving altered intestinal barriers, such as inflammatory bowel disease (IBD) [31]. Conversely, two volatile organic compounds (VOCs), hexanal and gammaterpinene, indicative of lipid peroxidation and decomposition of linoleic acid [32], exhibited decreased concentrations. ...
A healthy intestinal permeability facilitates the selective transport of nutrients, metabolites, water, and bacterial products, involving cellular, neural, hormonal, and immune factors. An altered intestinal permeability indicates pathologic phenotypes and is associated with the exacerbation of obesity and related comorbidities. To investigate the impact of altered permeability in obese patients undergoing a calorie-restrictive dietary regimen (VLCKD), we collected urinary and fecal samples from obese patients with both normal and altered permeability (determined based on the lactulose/mannitol ratio) before and after treatment. The analysis of volatile organic compounds (VOCs) aids in understanding the metabolites produced by the intestinal microbiota in this unique ecological niche. Furthermore, we examined clinical and anthropometric variables from the cohort and compared them to significant VOC panels. Consequently, we identified specific markers in the metabolomics data that differentiated between normal and altered profiles before and after the diet. These markers indicated how the variable contribution specifically accounted for interleukins and lipopolysaccharides (LPS). The targeted metabolomics experiment detected no differences in measured short-chain fatty acids (SCFA). In summary, our study evaluated metabolomic markers capable of distinguishing low-grade inflammation conditions, exacerbated in more advanced stages of obesity with altered intestinal permeability.
