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Dietary intake, energy metabolism, and excretory losses of adult male germfree Wistar rats
Abstract
Adult germfree rats excreted 87% more calories with the feces than comparable conventional rats, but this loss was compensated by an 18% higher intake. As a result, energy utilization of germfree and conventional rats was similar (148 and 143 kcal/kg/day, respectively), although the germfree rat metabolized only 71.9% of its dietary intake, versus the conventional rat's 80%. Germfree rats consumed 33% more water than conventional rats. Both excreted approximately 33% of water intake via feces and urine, but the germfree rat excreted 56% of this with the feces, the conventional rat only 15%. Cecectomy of the germfree rat reduced water loss via the feces, but the total daily excretion of fecal dry matter remained comparable to that of the intact germfree rat. The increase in fecal dry matter excretion demonstrated by the germfree rat can be largely accounted for in terms of water-soluble organic material. The data imply that the lower oxygen consumption of the germfree rat is not coupled to a reduction in metabolized energy, but may be an anomaly linked to cecal stasis and enlargement.
... The difference between these 2 values estimates the absorbed calories. As reported previously [44], GF animals ingested on average between 10% and 20% more standard chow compared to Oli-goMM12 and SPF mice ( Fig 2C). Correspondingly, GF animals also excreted a much larger dry mass of feces, while OligoMM12 mice produced an intermediate fecal mass and SPF mice excreted the least (Fig 2D). ...
... Since the early days of nutritional studies, there has been a clear interest to understand the role of microbiota in host morphology, physiology, and nutrition [54,55]. Pioneering work comparing GF rats with conventionally raised counterparts already described differences in food intake, energy extraction from diet, and energy expenditure by indirect calorimetry [44,56]. More recently, researchers have explored the effect of specific complex microbiota communities and how they influence energy metabolism and body composition in the host [9,57,58]. ...
... Interestingly, energy density of dry feces in GF mice was lower compared to OligoMM12 and SPF mice. Previous results have found a similar difference (approximately 0.1 kcal/g) when comparing GF and SPF rats under standard chow [44]. We theorized that this difference is due the contribution of energy stored in bacterial mass, which we estimated is in the range of 0.5 kcal/g per gram of feces. ...
The capacity of the intestinal microbiota to degrade otherwise indigestible diet components is known to greatly improve the recovery of energy from food. This has led to the hypothesis that increased digestive efficiency may underlie the contribution of the microbiota to obesity. OligoMM12-colonized gnotobiotic mice have a consistently higher fat mass than germ-free (GF) or fully colonized counterparts. We therefore investigated their food intake, digestion efficiency, energy expenditure, and respiratory quotient using a novel isolator-housed metabolic cage system, which allows long-term measurements without contamination risk. This demonstrated that microbiota-released calories are perfectly balanced by decreased food intake in fully colonized versus gnotobiotic OligoMM12 and GF mice fed a standard chow diet, i.e., microbiota-released calories can in fact be well integrated into appetite control. We also observed no significant difference in energy expenditure after normalization by lean mass between the different microbiota groups, suggesting that cumulative small differences in energy balance, or altered energy storage, must underlie fat accumulation in OligoMM12 mice. Consistent with altered energy storage, major differences were observed in the type of respiratory substrates used in metabolism over the circadian cycle: In GF mice, the respiratory exchange ratio (RER) was consistently lower than that of fully colonized mice at all times of day, indicative of more reliance on fat and less on glucose metabolism. Intriguingly, the RER of OligoMM12-colonized gnotobiotic mice phenocopied fully colonized mice during the dark (active/eating) phase but phenocopied GF mice during the light (fasting/resting) phase. Further, OligoMM12-colonized mice showed a GF-like drop in liver glycogen storage during the light phase and both liver and plasma metabolomes of OligoMM12 mice clustered closely with GF mice. This implies the existence of microbiota functions that are required to maintain normal host metabolism during the resting/fasting phase of circadian cycle and which are absent in the OligoMM12 consortium.
... BA act as surfactants and play a critical role in lipid absorption. Furthermore, BA have a positive impact on pancreatic function since they are able to trigger GLP-1 secretion, through their action as natural ligands on the Takeda G protein-coupled membrane receptor (TGR5) receptor expressed in intestinal L cells [119]. Both RYGB and VSG induce modifications of fasting and post-prandial BA serum concentration and composition [103,[120][121][122][123], whereas LAGB solely reduces serum BA [120]. ...
... Indirect proof of the involvement of BA on weight loss and improved glucose tolerance has been demonstrated using TGR5 and farnesoid X receptor (FXR) KO mice submitted to VSG, BA being another natural ligand for FXR [119]. In TGR5 −/− mice, VSG fails to induce improvements in body weight, fasting glycemia, and glucose tolerance [103], thus suggesting the importance of the TGR5 signaling pathway in the improvement of glucose homeostasis post-BS. ...
Le bypass Roux-en-Y (RYGB) permet d’induire une perte de poids massive et durable chez des patients atteints d’obésité sévère, ainsi qu’une rémission du diabète de type 2 (DT2) chez environ 50% des patients, bien que cette proportion diminue avec le temps. Notre équipe et d’autres ont décrit des modifications de la composition du microbiote intestinal (MI) à court et long terme après RYGB. Nous faisons l’hypothèse donc que ces modifications du MI participent à l’amélioration métabolique, et/ou la réaggravation du DT2 après quelques années. Grace à la description d’une cohorte de 175 patients DT2 ayant eu un RYGB et ayant été caractérisés au cours des 5 années post-RYGB, et montrons que plusieurs paramètres cliniques sont associés à la probabilité de rémission du T2D, ce qui nous a permis de développer un score de prédiction de la rémission du DT2 à 5 ans, le 5y-Ad-DiaRem. Nous avons ensuite réalisé des séquençages métagénomiques par MinION du MI de 100 de ces patients à 5 ans postopératoire. Par clustering hiérarchique, nous avons mis en évidence 2 groupes de sévérité du DT2. Nous montrons que ces groupes présentent des différences notoires de composition du MI. Afin d’apprécier la causalité liant amélioration métabolique post-RYGB et MI, nous avons réalisé une étude de transferts de matières fécales, qui a montré une modulation métabolique notable (tolérance au glucose, résistance à l’insuline) chez les animaux receveurs en lien direct avec l’état métabolique des donneurs. Nos résultats démontrent donc la contribution partielle du MI à l’amélioration métabolique post-RYGB, ce qui offre des perspectives prédictives, mécanistiques et thérapeutiques très précieuses.
... changes in drug efficacy [20]. Given that broad-spectrum antibiotics, a common method to cause a bacterial imbalance, may reduce the abundance and diversity of intestinal microorganisms [21], ampicillin and norfloxacin were selected to establish the pseudo-sterile model. Numerous studies have recognized that early intervention with antibiotics affects the metabolic system and increases the risk of obesity [22]. ...
... Numerous studies have recognized that early intervention with antibiotics affects the metabolic system and increases the risk of obesity [22]. However, a lower lipid level and a better OGTT result were observed in our pseudo-sterile model, which was consistent with earlier studies in germ-free mice [21,23] and some detrimental effects observed in healthy mice and HFD-fed mice [24,25]. We speculated that an unexpected macrobiotic imbalance was made by killing the most beneficial and harmful intestinal bacteria at the same time, thus affecting the body's energy metabolism. ...
Background
Intestinal microbiota is a novel drug target of metabolic diseases, especially for those with poor oral bioavailability. Nuciferine, with poor bioavailability, has an anti-hyperlipidemic effect at low dosages.
Purpose
In the present study, we aimed to explore the role of intestinal microbiota in the anti-hyperlipidemic function of nuciferine and identify the key bacterial targets that might confer the therapeutic actions.
Methods
The contribution of gut microbes in the anti-hyperlipidemic effect of nuciferine was evaluated by conventional and antibiotic-established pseudo-sterile mice. Whole-metagenome shotgun sequencing was used to characterize the changes in microbial communities by various agents.
Results
Nuciferine exhibited potent anti-hyperlipidemic and liver steatosis-alleviating effects at the doses of 7.5-30 mg/kg. The beneficial effects of nuciferine were substantially abolished when combined with antibiotics. Metagenomic analysis showed that nuciferine significantly shifted the microbial structure, and the enrichment of Akkermansia muciniphila was closely related to the therapeutic effect of nuciferine.
Conclusions
Our results revealed that gut microbiota played an essential role in the anti-hyperlipidemic effect of nuciferine, and enrichment of Akkermansia muciniphila represented a key mechanism through which nuciferine exerted its therapeutic effects.
... However, microbes reciprocally allow their host to use resources that they otherwise cannot digest or metabolize on their own, including essential vitamins. Consistent with this idea, the lack of a metabolically active gut microbiome causes caloric restriction in germ-free mice [67], and axenically grown C. elegans [68], showing a host's dependence on their microbiome for optimal nutrition. Similarly, our diet can dramatically impact our microbiome, as a Mediterraneanstyle diet rich in fruits and fibres, and low in fat, can have a positive impact on the gut microbial diversity and metabolism [69][70][71]. ...
The Human Microbiome Project was a research programme that successfully identified associations between microbial species and healthy or diseased individuals. However, a major challenge identified was the absence of model systems for studying host–microbiome interactions, which would increase our capacity to uncover molecular interactions, understand organ-specificity and discover new microbiome-altering health interventions. Caenorhabditis elegans has been a pioneering model organism for over 70 years but was largely studied in the absence of a microbiome. Recently, ecological sampling of wild nematodes has uncovered a large amount of natural genetic diversity as well as a slew of associated microbiota. The field has now explored the interactions of C. elegans with its associated gut microbiome, a defined and non-random microbial community, highlighting its suitability for dissecting host–microbiome interactions. This core microbiome is being used to study the impact of host genetics, age and stressors on microbiome composition. Furthermore, single microbiome species are being used to dissect molecular interactions between microbes and the animal gut. Being amenable to health altering genetic and non-genetic interventions, C. elegans has emerged as a promising system to generate and test new hypotheses regarding host–microbiome interactions, with the potential to uncover novel paradigms relevant to other systems.
This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.
... Accumulating research evidence highlights the decisive influence of host gut microbiota on the status of metabolic syndrome. Different researchers have reported microbiota modulation and concomitant anti-obesity effects of natural products [19][20][21][22][23]. Pathogenesis of obesity is closely associated with disturbances in the gut microbiota and variations in the ratio of two major intestinal microbial phyla (Firmicutes and Bacteroidetes) [24][25][26]. Nonetheless, comparisons of the gut bacterial communities between obese and lean subjects have produced conflicting results. In the present study, the abundance of Firmicutes with a concomitant decrease in the Bacteroidetes was found in the HFD-fed obese mice, which is consistent with several previous reports [20,27,28]. ...
... The two main types of bacteria that are known as Probiotics are Lactobacilli and bifidobacteria. The list of beneficial functions attributed to intestinal bacteria continues to grow and includes regulation of intestinal angiogenesis [4], nutrient processing [5], development of gut-associated lymphoid tissues [GALT] [6], induction of mucosal immunity [7], oral tolerance [8], and diversification of the preimmune Ab repertoire [9,10] in their studies have indicated that the lack of proper connections between human host and the bacteria contributes to the prevalence of allergies and Crohn's disease in developed countries [11] have indicated that these intestinal microflora has been shown to contribute to antigenic exclusion. The resident microflora [probiotics] prevents adherence of disease-causing antigens by competing for nutrients and adhesion sites in the Gastrointestinal Tract [GUT], by producing antimicrobial agents, and by increasing production of specific antibody secreting cells and mucus. ...
The human gastrointestinal tract comprises of mouth, pharynx, esophagus and stomach, the small intestines, large intestines and the anus.
... The first evidence for a link between gut microbiota and obesity was from studies of germ-free mice. In 1983, Wostmann et al. first discovered that germ-free rats needed more energy to maintain their body weight compared to wild rats, but the precise mechanism was unknown at the time (35). In 2004, Gordon et al. observed that gut microbiota can affect energy absorption from the diet and energy storage in mice, and found that the proportion of Firmicutes was higher and the proportion of Bacteroidetes was lower in the guts of obese people (36). ...
Obesity, a chronic metabolic disease with a complex pathophysiology, is caused by several variables. High-fat diets lead to the disruption of the gut microbiota and impaired gut barrier function in obese people. The dysbiosis and its metabolites through the intestinal barrier lead to an imbalance in energy metabolism and inflammatory response, which eventually contributes to the development of chronic diseases such as diabetes, hypertension, and cardiovascular disease. Current medicines are therapeutic to obesity in the short term; however, they may bring significant physical and emotional problems to patients as major side effects. Therefore, it is urgent to explore new therapeutic methods that have definite efficacy, can be taken for a long time, and have mild adverse effects. Numerous studies have demonstrated that traditional Chinese medicine (TCM) can control the gut microbiota in a multi-targeted and comprehensive manner, thereby restoring flora homeostasis, repairing damaged intestinal mucosal barriers, and eventually curbing the development of obesity. The active ingredients and compounds of TCM can restore the normal physiological function of the intestinal mucosal barrier by regulating gut microbiota to regulate energy metabolism, inhibit fat accumulation, affect food appetite, and reduce intestinal mucosal inflammatory response, thereby effectively promoting weight loss and providing new strategies for obesity prevention and treatment. Although there are some studies on the regulation of gut microbiota by TCM to prevent and treat obesity, all of them have the disadvantage of being systematic and comprehensive. Therefore, this work comprehensively describes the molecular mechanism of obesity mediated by gut microbiota based on the research state of obesity, gut microbiota, and TCM. A comprehensive and systematic summary of TCM targeting the regulation of gut microbiota for the treatment of obesity should be conducted in order to provide new strategies and ideas for the treatment of obesity.
... Germ-free mice are microbiologically sterile from birth and are maintained in a sterile environment. Illustrating the importance of the microbiota for nutrition, germ-free animals must consume 30% more calories per day than conventional animals to maintain body weight [38]. Table 3 demonstrated the effects of Virus. ...
Microorganisms or microbes are microscopic organisms that exist as unicellular, multicellular, or cell clusters. Microorganisms are widespread in nature and are beneficial to life, but some can cause serious harm. They can be divided into five major types: Bacteria, Archaea, Fungi, Protozoa, and Viruses. Microbes are everywhere in the biosphere, and their presence invariably affects the environment that they are growing in. Microorganisms are beneficial in producing oxygen in environment, decomposing organic material, medicine, providing nutrients for plants, and maintaining human health, but some can be pathogenic and cause diseases in plants and humans. They perform a key role and act as main engineers in governing all ecological processes. They act as universal catalyst and provide ecological transformations. Regardless of whether they influence human health and welfare favorably or unfavorably, microorganisms are capable of profound influences on life. That is to say, it is an integral part of our lives, and therefore acquiring knowledge about it should also be essential and the main thing.
... Wostmann et al. ont montré en 1983 que les rats axéniques avaient besoin d'un apport calorique supplémentaire de 30% pour maintenir leur poids par rapport à des souris conventionnelles [212]. Plus [215]. ...
Le microbiote intestinal est un écosystème de microorganismes dont les nombreuses fonctions digestives et immunitaires le rendent indispensable à la bonne santé de son hôte. Une susceptibilité génétique associée à des perturbations environnementales peut rompre cet équilibre et entrainer une dysbiose. L’inflammation chronique en résultant se traduit en différents troubles locaux et systémiques. Ainsi la dysbiose a été mise en cause dans la physiopathologie des maladies inflammatoires chroniques de l’intestin et également au développement de troubles métaboliques associés à l’obésité.Les peptides antimicrobiens sont des molécules du système immunitaire innée ayant des fonctions de contrôle de la population bactérienne au niveau de la barrière intestinale et empêchant le contact direct entre celles-ci et les cellules épithéliales.L’objectif de cette thèse est d’étudier le potentiel thérapeutique des peptides antimicrobiens dans le traitement de maladies liées à la dysbiose comme les MICI et le syndrome métabolique. Pour cela Lactococcus lactis, une bactérie lactique interagissant de manière transitoire avec la barrière épithéliale intestinale, a été utilisée comme vecteur de la molécule d’intérêt. Durant cette thèse j’ai pu établir que la cathélicidine humaine (hCAP18) et REG3A avaient un impact sur le microbiote et amélioraient les symptômes de la colite induite et de l’obésité chez le rongeur.
... Despite clear results arising from animal models, the role of SCFA in altering the energy harvest has been less elucidated in humans. An early study reported a lower faecal energy excretion in those with obesity when compared with lean ones [37]. Among others, Bacteroidetes are the main contributors to the production of SCFA, with changes in their abundance impacting the level of SCFA. ...
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease, affecting one-third of the population worldwide. Despite many medications being in the pipeline to treat the condition, there is still no pharmaceutical agent licensed to treat the disease. As intestinal bacteria play a crucial role in the pathogenesis and progression of liver damage in patients with NAFLD, it has been suggested that manipulating the microbiome may represent a therapeutical option. In this review, we summarise the latest evidence supporting the manipulation of the intestinal microbiome as a potential therapy for treating liver disease in patients with NAFLD.
... In the last 50 years, obesity has become a major public health concern worldwide, with nearly 40% of the world's adult population estimated to be overweight in 2016 [body mass index (BMI) of ≥ 25 kg/m 2 ], of whom over 10% were affected by obesity (BMI ≥ 30 kg/m 2 ), representing a prevalence rate three times higher than in 1975 [139] . The role of the intestinal microbiota in metabolism was assessed for the first time using GF rodent models in a historical 1983 study [140] . ...
Alterations in the intestinal microbiota are associated with various human diseases of the digestive system, including obesity and its associated metabolic diseases, inflammatory bowel diseases (IBD), and colorectal cancer (CRC). All three diseases are characterized by modifications of the richness, composition, and metabolic functions of the human intestinal microbiota. Despite being multi-factorial diseases, studies in germ-free animal models have unarguably identified the intestinal microbiota as a causal driver of disease pathogenesis. However, for an increased mechanistic understanding of microbial signatures in human diseases, models require detailed refinement to closely mimic the human microbiota and reflect the complexity and range of dysbiosis observed in patients. The transplantation of human fecal microbiota into animal models represents a powerful tool for studying the causal and functional role of the dysbiotic human microbiome in a pathological context. While human microbiota-associated models were initially employed to study obesity, an increasing number of studies have applied this approach in the context of IBD and CRC over the past decade. In this review, we discuss different approaches that allow the functional validation of the bacterial contribution to human diseases, with emphasis on obesity and its associated metabolic diseases, IBD, and CRC. We discuss the utility of simple models, such as in vitro fermentation systems of the human microbiota and ex vivo intestinal organoids, as well as more complex whole organism models. Our focus here lies on human microbiota-associated mouse models in the context of all three diseases, as well as highlighting the advantages and limitations of this approach.
... Similarly, colonization of GF mice leads to weight gain and increased adiposity (44). At least part of these weight differences is due to increased energy harvest from the diet (45). The gut microbiota metabolizes otherwise indigestible complex carbohydrates leading to the formation of short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. ...
We are host to an assembly of microorganisms that vary in structure and function along the length of the gut and from the lumen to the mucosa. This ecosystem is collectively known as the gut microbiota and significant efforts have been spent during the past two decades to catalog and functionally describe the normal gut microbiota and how it varies during a wide spectrum of disease states. The gut microbiota is altered in several cardiometabolic diseases and recent work has established microbial signatures that may proceed disease. However, most research has focused on identifying associations between the gut microbiota and human diseases states and to investigate causality and potential mechanisms using cells and animals. Since the gut microbiota functions on the intersection between diet and host metabolism, and can contribute to inflammation, several microbially produced metabolites and molecules may modulate cardiometabolic diseases. Here we discuss how the gut bacterial composition is altered in, and can contribute to, cardiometabolic disease, as well as how the gut bacteria can be targeted to treat and prevent metabolic diseases.
... Wostmann et al. were the first ones to reveal the correlation between gut microbiota and obesity on germ-free (GF) rats' model. 11 It was found that adult GF rats excrete with feces on 87% more calories than the control group. according to PubMed data, gut microbiota is the research area, which has received the greatest boost in its development during the last two decades. ...
Interaction between intestinal microbiota and obesity is becoming abundantly according to current many scientific investigations. In this article, probiotic therapy was offered as the promising strategy of metabolic disorders control through the recovery of microbiota composition and health maintenance with the help of impact on the abovementioned mechanisms. First, this therapy is safe, with minimal side effects, well-tolerated, and appropriate for long-term use. Second, it can improve body mass, glucose, and fat metabolism, increase insulin sensitivity, and decrease systemic chronic inflammation. In conclusion, the restorative role of gut microbiota on metabolic disorders and associated diseases could open new ways in the treatment of obesity, insulin resistance, and type 2 diabetes.
... It was shown in in vivo studies that animals depleted of microbes had increased susceptibility to infection and serious defects of mucosal immune system [50]. Moreover, the microbiota is responsible for the immune system modulation by the regulation of inflammatory cytokines, plays a role in metabolic activity regulating the production of short chain fatty acids and influences significantly of host fat storage [51][52][53]. ...
Irritable bowel syndrome (IBS) is a common, chronic, functional disorder with a large impact on world population. Its pathophysiology is not completely revealed; however, it is certain that dysregulation of the bidirectional communications between the central nervous system (CNS) and the gut leads to motility disturbances, visceral hypersensitivity, and altered CNS processing characterized by differences in brain structure, connectivity and functional responsiveness. Emerging evidence suggests that gut microbiota exerts a marked influence on the host during health and disease. Gut microbiome disturbances can be also important for development of IBS symptoms and its modulation efficiently contributes to the therapy. In this work, we review the current knowledge about the IBS therapy, the role of gut microbiota in pathogenesis of IBS, and we discuss that its targeting may have significant impact on the effectiveness of IBS therapy.
... Additionally, Wostmann first discovered that the growth rate of GF mice was slower than normal mice. Gut microbiota also contributes to fat deposition (33). Bäckhed et al. (19) proved that gut microbiota could inhibit the expression of LPL cycle inhibitor, ANGPTL4, in the intestine. ...
Increasing studies have shown that obesity is the primary cause of cardiovascular diseases, non-alcoholic fatty liver diseases, type 2 diabetes, and a variety of cancers. The dysfunction of gut microbiota was proved to result in obesity. Recent research indicated ANGPTL4 was a key regulator in lipid metabolism and a circulating medium for gut microbiota and fat deposition. The present study was conducted to investigate the alteration of gut microbiota and ANGPTL4 expression in the gastrointestinal tract of mice treated by the high-fat diet. Ten C57BL/6J mice were randomly allocated to two groups and fed with a high-fat diet (HFD) containing 60% fat or a normal-fat diet (Control) containing 10% fat. The segments of ileum and colon were collected for the determination of ANGPTL4 expression by RT-qPCR and immunohistochemical analysis while the ileal and colonic contents were collected for 16S rRNA gene sequencing. The results showed HFD significantly increased mice body weight, epididymal fat weight, perirenal fat weight, liver weight, and the lipid content in the liver (P < 0.05). The relative expression of ANGPTL4 and the ANGPTL4-positive cells in the ileum and colon of mice was significantly increased by HFD treatment. Furthermore, 16S rRNA gene sequencing of the ileal and colonic microbiota suggested that HFD treatment changed the composition of the gut microbiota. The ratio of Firmicutes to Bacteroidetes and the abundance of Allobaculum was significantly higher in the HFD group than in the Control group while the abundance of Adlercreutzia, Bifidobacterium, Prevotellaceae UCG-001, and Ruminococcus was significantly decreased. Interestingly, the abundance of Allobaculum was positively correlated with the expression of ANGPTL4. These findings provide a theoretical foundation for the development of strategies to control the obesity and related diseases by the regulation of ANGPTL4 and gut microbiota.
... 11 Moreover, despite consuming 30% more calories than conventionally raised mice to maintain comparable body weight, germ-free mice still show deficits in digestion, nutrient absorption, and metabolism. 7,13 Although germ-free mice retain immune function, their immune capabilities are blunted, with decreased or absent levels of certain bacterial recognition receptors, such as toll-like receptors, reduced antibody secretion, and smaller immune surveillance centers called Peyer's patches within the gut. 10,14 Conventionalization of germ-free mice reverses many of these anatomic and physiologic deficiencies. ...
Years of coevolution with resident microbes has made them an essential component of health. Yet, little is known about oral commensal bacteria’s contribution to and role in the maintenance of oral health and homeostasis. Commensal bacteria are speculated to play a host protective role in the maintenance of health. In this review, we describe and provide examples of the coordinate regulation that occurs between oral commensal bacteria and the host innate immune response to modulate and maintain oral homeostasis.
... In general, greater than 90% of SCFA produced are absorbed in the lower gut (Bindelle et al., 2008) and it is estimated that SCFA contribute to approximately 25% of the maintenance energy requirement of the pig (Yen et al., 1991;Grieshop et al., 2001). In germ-free rats it has been shown that there is a 30% increase in energy intake required for maintenance compared to rats with an intact intestinal microbial population (Wostmann et al., 1983). ...
... The IM provides the host with key enzymes for different metabolic processes, including complex polysaccharide catabolism, vitamin and amino acid biosynthesis, and bile acid deconjugation and dehydroxylation, which control lipid solubilization and absorption [43]. For this reason, as a whole, it is assumed that IM increases host ability to extract energy from food and promotes fat storage [47][48][49]. The IM also participates in the regulation of the energy balance through the interaction with the central nervous system, acting on the synthesis and activity of hormones and neuropeptides [43]. ...
Obesity is a chronic disease resulting from an imbalance between energy intake and expenditure. The growing relevance of this metabolic disease lies in its association with other comorbidities. Obesity is a multifaceted disease where intestinal hormones such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), produced by enteroendocrine cells (EECs), have a pivotal role as signaling systems. Receptors for these hormones have been identified in the gut and different brain regions, highlighting the interconnection between gut and brain in satiation mechanisms. The intestinal microbiota (IM), directly interacting with EECs, can be modulated by the diet by providing specific nutrients that induce environmental changes in the gut ecosystem. Therefore, macronutrients may trigger the microbiota–gut–brain axis (MGBA) through mechanisms including specific nutrient-sensing receptors in EECs, inducing the secretion of specific hormones that lead to decreased appetite or increased energy expenditure. Designing drugs/functional foods based in bioactive compounds exploiting these nutrient-sensing mechanisms may offer an alternative treatment for obesity and/or associated metabolic diseases. Organ-on-a-chip technology represents a suitable approach to model multi-organ communication that can provide a robust platform for studying the potential of these compounds as modulators of the MGBA.
... The symbiotic relationship between the gut microbiota and the host is the result of a dynamic and beneficial equilibrium between both players, and exponentially growing studies focus on the fascinating interkingdom of communication pathways developed between prokaryotic and eukaryotic cells in health and disease conditions Figure 2. Microorganisms harboring the human gastrointestinal tract produce many pleiotropic compounds, such as vitamins, gas, organic acids, bile salts, and bacteriocin, influencing in the host innate and acquired immunity maturation and homeostasis, energy, and metabolism and maintenance of the epithelial barrier function, providing defense against pathogens [26]. GF animals display significant differences in metabolite levels in different biological tissues including the gut, if compared with conventionally reared controls, necessitating a higher caloric intake to maintain the same body weight and are prone to vitamin deficiencies requiring dietary supplementation [211,212]. Dysbiosis associated with IBD may alter the bacterial metabolic profile influencing the host organism homeostasis with prominent alterations in the levels of metabolites with immunomodulatory properties, such as SCFAs, bile acids, and tryptophan metabolites predisposing to mucosal inflammation [213]. Defects in the production of protective bacterial metabolites may adversely influence gut-brain communication favoring gutbrain disorders associated with IBD. ...
The complex bidirectional communication system existing between the gastrointestinal tract and the brain initially termed the “gut–brain axis” and renamed the “microbiota–gut–brain axis”, considering the pivotal role of gut microbiota in sustaining local and systemic homeostasis, has a fundamental role in the pathogenesis of Inflammatory Bowel Disease (IBD). The integration of signals deriving from the host neuronal, immune, and endocrine systems with signals deriving from the microbiota may influence the development of the local inflammatory injury and impacts also more distal brain regions, underlying the psychophysiological vulnerability of IBD patients. Mood disorders and increased response to stress are frequently associated with IBD and may affect the disease recurrence and severity, thus requiring an appropriate therapeutic approach in addition to conventional anti-inflammatory treatments. This review highlights the more recent evidence suggesting that alterations of the microbiota–gut–brain bidirectional communication axis may concur to IBD pathogenesis and sustain the development of both local and CNS symptoms. The participation of the main microbial-derived metabolites, also defined as “postbiotics”, such as bile acids, short-chain fatty acids, and tryptophan metabolites in the development of IBD-associated gut and brain dysfunction will be discussed. The last section covers a critical evaluation of the main clinical evidence pointing to the microbiome-based therapeutic approaches for the treatment of IBD-related gastrointestinal and neuropsychiatric symptoms.
... Gut microbiota plays an important role in the fat synthesis and storage. Since germ-free mice require high energy to achieve and sustain target body mass compared to wild mice, a strong association of gut microbiota with energy expenditure and body weight is anticipated (Cani et al., 2019;Wostmann et al., 1983). Noteworthy, supplementation of butyrate reported to abrogate the high fat diet generated obesity and insulin resistance in mice (Gao et al., 2009;Lin et al., 2012;Muscogiuri et al., 2019). ...
Ischemic brain injury is a serious neurological complication, which accrues an immense activation of neuroinflammatory responses. Several lines of research suggested the interconnection of gut microbiota perturbation with the activation of proinflammatory mediators. Intestinal microbial communities also interchange information with the brain through various afferent and efferent channels and microbial by-products. Herein, we discuss the different microelements of gut microbiota and its connection with the host immune system and how change in immune-microbial signatures correlates with the stroke incidence and post-injury neurological sequelae. The activated inflammatory cells increase the production of proinflammatory cytokines, chemokines, proteases and adhesive proteins that are involved in the systemic inflammation, blood brain barrier disruption, gut dysbiosis and aggravation of ischemic brain injury. We suggest that fine-tuning of commensal gut microbiota (eubiosis) may regulate the activation of CNS resident cells like microglial, astrocytes, mast cells and natural killer cells.
... The main reason for the progression of aging, Elie Mechnikov believed, was the formation of compounds from microbial intestinal putrefaction (Metchnikoff and Mitchell, 1908). The correlation between microbiota and host's obesity was first described by Wostmann et al. (Wostmann et al., 1983). Studies have shown that germ-free (GF) rodents excrete 87% more calories in their feces than normal rats. ...
The worldwide prevalence of obesity more than doubled between 1980 and 2014. The most frequent cause which leads to the obesity development is a dysbalance between energy intake and energy expenditure. In this complex process genetic susceptibility, environmental and lifestyle factors are involved. Consequently, the gut microbiota is gaining significant research interest in relation to obesity and associated metabolic disorders in an attempt to better understand the etiology of obesity and potentially new methods of its prevention and treatment.
... One human study showed a significant association between the presence of steatohepatitis and an increased percentage Firmicutes and a reduced percentage of Bacteroidetes (two predominant bacterial phyla colonizing the healthy human large intestine) [141], and the increase of the Firmicutes/Bacteroidetes ratio was reported associated with increased energy harvest from the diet [142]. SCFAs not only provide extra energy to the host (about 30% of hepatic energy supply) [143] but also impact satiety and insulin signaling by stimulating the production of peptide YY (PYY) and GLP-1 in the intestine [144]. The insulin-mediated fat accumulation could be suppressed by the interaction of SCFAs and their receptors, G-protein-coupled receptors (GPCRs), in the gut, skeletal muscle, adipose tissue and the liver [145]. ...
Non-alcoholic fatty liver disease (NAFLD) represents the leading cause of chronic liver disease worldwide and the anticipated health burden is huge. There are limited therapeutic approaches for NAFLD now. It’s imperative to get a better understanding of the disease pathogenesis if new treatments are to be discovered. As the hepatic manifestation of metabolic syndrome, this disease involves complex interactions between different organs and regulatory pathways. It’s increasingly clear that brain, gut and adipose tissue all contribute to NAFLD pathogenesis and development, in view of their roles in energy homeostasis. In the present review, we try to summarize currently available data regarding NAFLD pathogenesis and to lay a particular emphasis on the inter-organ crosstalk evidence.
... At the same time, some plant foods such as corn and sugar cane is added as an indispensable supplement during the feeding process (Zhiyong et al., 2018). A carnivorous animal such as the dhole does not digest polysaccharides found in plant fiber well but we found a high abundance of Bacteroidetes in its intestinal microbiota, which can produce a series of enzymes that digest these polysaccharides to provide energy to the host (Wostmann et al., 1983;Younes et al., 2001;Lópezmondéjar et al., 2016;Xiong et al., 2018). ...
The co-evolution of gut microbes and the host plays a vital role in the survival and reproduction of the host. The dhole ( Cuon alpinus ) has been listed as endangered species by the International Union for Conservation of Nature; therefore, conservation and effective breeding of dholes are essential. Effective estrus can promote reproduction. However, little is known about the relative contribution of estrus in shaping the structure and the functions of fecal microbiota. Here, we investigated the potential association between estrus and the fecal microbiota in dholes using shotgun metagenomic sequencing. We found that the estrus stages in dholes vary significantly in terms of gut bacterial composition and microbiome metabolism and function. Compared with that of non-estrus, adult dholes, the microbiome of estrus adult dholes had a significantly higher abundance of Bacillus faecalis and Veillonella , which play a key role in the synthesis of sex hormones and nucleic acids, energy production, and reproductive cell division. The insulin and energy metabolism-related pathways are significantly enhanced in the gut microbes and the related gluconeogenic enzymes are significantly enriched during estrus. These findings suggest that the structure and metagenome of the fecal microbiome during estrus have a significant effect in promoting estrus in dholes, thus providing a new perspective for dhole conservation.
... It has been found that bacterial diversity in the gut promote host development and growth by enabling greater resource acquisition and preventing domination by certain bacteria (Ley et al. 2006;Lozupone et al. 2012;Foster et al. 2017). For example, studies have demonstrated that germ-free animals require a higher calorific intake to attain the same growth as hosts with a normal microbial diversity (Wostmann et al. 1983;Bäckhed et al. 2004;Shin et al. 2011;Sommer & Bäckhed 2013). Conversely, it has been suggested that a reduced diversity in the gut microbiota may increase growth and accelerate host development. ...
The development of gut microbiota during ontogeny in vertebrates is emerging as an important process influencing physiology, immune system, health, and adult fitness. However, we have little knowledge of how the gut microbiome is colonised and develops in non-model organisms, and to what extent microbial diversity and specific taxa influence changes in fitness-related traits. Here, we used 16S rRNA gene sequencing to describe the successional development of the faecal microbiota in juvenile ostriches ( Struthio camelus ; n = 71) over their first three months of life, during which time a five-fold difference in weight was observed. We found a gradual increase in microbial diversity with age, an overall convergence in community composition among individuals, multiple colonisation and extinction events, and major taxonomic shifts coinciding with the cessation of yolk absorption. In addition, we discovered significant but complex associations between juvenile growth and microbial diversity, and identified distinct bacterial groups that had positive (Bacteroidaceae) and negative (Enterobacteriaceae, Enterococcaceae, Lactobacillaceae) correlations with the growth of individuals at specific ages. These results have broad implications for our understanding of the development of gut microbiota and its association with juvenile growth.
... Obesity is a risk factor for diabetes mellitus, dyslipidemia, and several immune-related disorders such as inflammatory bowel diseases and cancers. As early as in 1983, Wostmann and his colleagues have found that the germ-free rats consumed more calories than normal rats (Wostmann, Larkin, Moriarty, & Bruckner-Kardoss, 1983). Also, there was a significant difference in the composition of intestinal microbiota between obese patients and healthy volunteers. ...
Gut microbiota plays a key role in the maintenance of human health. In most cases, carbohydrates can be fermented by gut microbiota as substrates. By such degradation reaction, the abundances, activities and metabolite production of gut microbiota will be regulated and thus prevent the occurrence of human diseases such as glycolipid metabolism disorders, enteric abnormality, aging and neurodegeneration, cancers and depression. In this paper, we reviewed the roles of carbohydrates in promoting human health through gut microbial regulation, as well as further studies on the regulatory mechanism and potential application of carbohydrates, which need to be strengthened in the future.
... The involvement of SCFAs and energy harvest in obesity was first brought to light in seminal studies performed by Bäckhed et al., in which GF mice were protected against diet induced obesity compared to their wild-type littermates [15]. In keeping with this result, GF mice also displayed reduced concentrations of intestinal SCFAs [28] and doubled their caloric excretion of undigested polysaccharides in feces and urine compared to conventional animals [29], supporting the causal role of gut bacteria in converting these substrates into a bioavailable energy source for the host. Furthermore, colonization of these mice with a healthy microbiome was sufficient to increase intestinal SCFAs and induce adiposity [15], while colonization with microbiota from an obese donor doubled this subsequent gain in fat mass [9]. ...
Obesity has become a global epidemic and a public health crisis in the Western World, experiencing a threefold increase in prevalence since 1975. High-caloric diets and sedentary lifestyles have been identified as significant contributors to this widespread issue, although the role of genetic, social, and environmental factors in obesity’s pathogenesis remain incompletely understood. In recent years, much attention has been drawn to the contribution of the gut microbiota in the development of obesity. Indeed, research has shown that in contrast to their healthier counterparts the microbiomes of obese individuals are structurally and functionally distinct, strongly suggesting microbiome as a potential target for obesity therapeutics. In particular, pre and probiotics have emerged as effective and integrative means of modulating the microbiome, in order to reverse the microbial dysbiosis associated with an obese phenotype. The following review brings forth animal and human research supporting the myriad of mechanisms by which the microbiome affects obesity, as well as the strengths and limitations of probiotic or prebiotic supplementation for the prevention and treatment of obesity. Finally, we set forth a roadmap for the comprehensive development of functional food solutions in combatting obesity, to capitalize on the potential of pre/probiotic therapies in optimizing host health.
... Humans cannot degrade most plant polysaccharides, which instead, can be utilized by the gut bacteria, producing SCFAs that are important energy substrates [80]. Direct evidence supporting the role of the gut microbiome in energy balance is that germ-free rats have reduced intestinal levels of SFCAs and doubled excretion of calories through urine and feces [98,99]. It is suggested that the capacity for the energy harvest of the gut microbiome is correlated with its microbial composition [100], specifically, the ratio of two major phyla Firmicutes and Bacteroidetes. ...
The human gut microbiome can be easily disturbed upon exposure to a range of toxic environmental agents. Environmentally induced perturbation in the gut microbiome is strongly associated with human disease risk. Functional gut microbiome alterations that may adversely influence human health is an increasingly appreciated mechanism by which environmental chemicals exert their toxic effects. In this review, we define the functional damage driven by environmental exposure in the gut microbiome as gut microbiome toxicity. The establishment of gut microbiome toxicity links the toxic effects of various environmental agents and microbiota-associated diseases, calling for more comprehensive toxicity evaluation with extended consideration of gut microbiome toxicity.
Objectives
Gut microbiota increases energy availability through fermentation of dietary fibers to short-chain fatty acids in conventionally raised mice. Energy deficiency in germ-free (GF) mice increases glucagon-like peptide-1 (GLP-1) levels, which slows intestinal transit. To further analyze the role of GLP-1-mediated signaling in this model of energy deficiency, we re-derived mice lacking GLP-1 receptor (GLP-1R KO) as GF.
Methods
GLP-1R KO mice were rederived as GF through hysterectomy and monitored for 30 weeks. Mice were subjected to rescue experiments either through feeding an energy-rich diet or colonization with a normal cecal microbiota. Histology and intestinal function were assessed at different ages. Intestinal organoids were assessed to investigate stemness.
Results
Unexpectedly, 25% of GF GLP-1R KO mice died before 20 weeks of age, associated with enlarged ceca, increased cecal water content, increased colonic expression of apical ion transporters, reduced number of goblet cells and loss of colonic epithelial integrity. Colonocytes from GLP-1R KO mice were energy-deprived and exhibited increased ER-stress; mitochondrial fragmentation, increased oxygen levels and loss of stemness. Restoring colonic energy levels either by feeding a Western-style diet or colonization with a normal gut microbiota normalized gut phenotypes and prevented lethality.
Conclusions
Our findings reveal a heretofore unrecognized role for GLP-1R signaling in the maintenance of colonic physiology and survival during energy deprivation.
The gut microbiome is a community of commensal microbes in the gastrointestinal tract that are ecologically, physiologically, and symbiotically associated with the host from the early days of life. Gut microbiota is analogous to endocrine glands. Microbial colonies in the gut produce certain microbial metabolites from nutrient metabolism. These gut-derived metabolites regulate the host’s health and disease by influencing immunity and physiology. Gut microbiota protects the intestinal environment from invading non-native pathogens by immune modulation and direct competition with pathogens for nutrient access. The gut microbiome is essential in regulating the immune system through interaction with its microbial surface antigens and metabolites. Gut microbiota is coevolved with host development and varies among individuals. The proportion of gut microbiota is constant during health. This constancy is affected by factors such as diet, medications, environment, and mental status regulating the host’s health. The dysbiotic microbiome is a risk signature of immune dysfunction and disorders in host physiology. The gut microbiome modulates the immune system locally and systematically; thus, its composition balances an individual’s health and disease conditions. This chapter reviewed the link between microbiome composition and its outcome on host physiology, immune system development, metabolic syndromes, and cancer outcomes.
Germ-free animals refer to the animals in which bacteria, fungi, actinomycetes,
mycoplasma, chlamydia, spirochetes, rickettsia, viruses, protozoa, and parasites cannot be
detected in any part of the body and in vitro by modern technologies. Since germ-free animals
do not carry any microorganism, they can be modeled into the animals carrying specific
microorganisms. Because of the dormant immune system, germ-free animals are extremely
sensitive to microbial infections. A variety of gnotobiotic animal models can be established for
specific microbial infection experiments and pathogenic mechanism research. As a key tool,
germ-free animals are pivotal in studying the relationship between microbiome and diseases
and play an irreplaceable role in the research on the relationship between microbiome and host
health and the mechnisms of infections. We briefly introduce germ-free animals and review the
applications of germ-free animals in the research on the mechanisms of host-microorganism
interactions.
Obesity and diabetes are closely related metabolic disorders that have become major public health concerns worldwide. Over the past few decades, numerous studies have explored the underlying mechanisms of these disorders and identified various risk factors, including genetics, lifestyle, and dietary habits. Traditional Chinese Medicine (TCM) has been increasingly recognized for its potential to manage obesity and diabetes. Weight loss is difficult to sustain, and several diabetic therapies, such as sulfonylureas, thiazolidinediones, and insulin, might make it harder to lose weight. While lifestyle changes should be the primary approach for people interested in lowering weight, drugs are also worth investigating. Since some of the newer glucose-lowering medications that cause weight loss, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), are additionally utilized or are under consideration for use as anti-obesity drugs, the frontier between glucose-lowering medication and weight loss drugs appears to be shifting. This review provides an overview of the literature on the underlying mechanisms of obesity and diabetes and the prospect of TCM in their management. We discuss the various TCM interventions, including acupuncture, herbal medicine, and dietary therapy, and their effects on metabolic health. We also highlight the potential of TCM in regulating gut microbiota, reducing inflammation, and improving insulin sensitivity. The findings suggest that TCM may provide a promising approach to preventing and managing obesity and diabetes. However, further well-designed studies are needed to confirm the efficacy and safety of TCM interventions and to elucidate their underlying mechanisms of action.
Triptolide (TP) is a toxic component of Tripterygium wilfordii Hook. f. that exhibits liver and gastrointestinal toxicity. However, TP-induced liver injury varies between individuals via an unknown mechanism, which limits the safe clinical application of TP. Herein, we aimed to study the mechanism underlying the regulation of TP-induced liver injury via the gut-liver axis using a multi-omics technique. C57BL/6 mice were administered with TP at 800 µg/kg. We also constructed a mouse model based on the male C57BL/6 gut microbiota with quadruple antibiotics. 16S rRNA gene sequencing, hematoxylin and eosin staining, and biochemical analyses were used to analyze the intestinal microbiota composition in stool samples and TP-induced hepatotoxicity and enterotoxicity. Proteomics and targeted metabonomics were performed to analyze key proteins related to intestinal injury and differential liver metabolic markers. Gut microbiota Lactobacillus and Bacteroides were related to TP hepatotoxicity, while the Lactobacillus rhamnosus or Bacteroides fragilis colonization alleviated TP-induced liver and ileum damage after gut microbiota disorder. Multi-omics analyses showed that the TP caused changes in genes related to intestinal and liver immune responses. Gut microbiota disorder amplified related immune responses, causing changes in intestinal immune barrier-related proteins REG3B and REG3G and changes to liver metabolites via the gut-liver axis. Thus, the gut microbiota (via the gut–liver axis) plays an important role in liver injury induced by TP, allowing a better interpretation of TP-induced hepatotoxicity.
Obesity can be considered a multifactorial disease, with a variety of
origins and a multitude of genes involved, affecting 300-400 million
people worldwide. In extreme cases, obesity is a life-threatening condition,
requiring drastic treatments, such as bariatric surgery. This disease can be
triggered by genetic syndromes, but is often the result of enteric dysbiosis,
caused by either an inadequate diet or simply gluttony. This review
focuses on particular biochemical and genetic markers that, together with
enteric microorganisms, are believed to generate the current global obesity
epidemic.
Cancer is a substantial global health problem both in humans and animals with a consistent increase in mortality and incidence rate. The commensal microbiota has been involved in the regulation of several physiological and pathological processes, both within the gastrointestinal system and at distant tissue locations. Cancer isn't an exception, and different aspects of the microbiome have been described to have anti- or pro-tumour effects. Using new techniques, for example high-throughput DNA sequencing, microbial populations of the human body have been largely described and, in the last years, studies more focused on companions' animals have emerged. In general, the recent investigations of fecal microbial phylogeny and functional capacity of the canine and feline gut have shown similarities with human gut. In this translational study we will review and summarize the relation between the microbiota and cancer, in humans and companion animals, and compare their resemblance in the type of neoplasms already studied in veterinary medicine: multicentric and intestinal lymphoma, colorectal tumours, nasal neoplasia and mast cell tumours. In the context of One Health, microbiota and microbiome integrative studies may contribute to the understanding of the tumourigenesis process, besides offering an opportunity to develop new diagnostics and therapeutic biomarkers both for veterinary and human oncology.
The most popular approach to measure key functions of any living entity is to remove it and then study the consequences of its removal. Microorganisms influence their host in several manners and their role can be studied by eliminating them from their host and observe the host’s response, in their absence. Numerous studies have justified the vital role of microbiota in human health and disease development. Germ-free (GF) animal models are useful tools to improve our understanding of the host–microbiota relationship in vivo. Although different animal models, lacking microbiota (partially or completely) have been extensively used in research but germ-free (GF) mice are the most widely used rodent model in human research due to its close proximity to humans. In modern research, GF technology is one of the most attractive and informative tools for getting insights into host’s microbial community. Each body part harbors unique microorganisms with unique functions. Because of the advancement of microbial characterization techniques, the human microbiota community is expanding day by day. GF mice model can efficiently reveal the role of these valuable partners of humans. In spite of its high cost and obligation of skilled experts, GF research is a hot field for investigators and has a huge possibility for future applications. The present book chapter is a summary of the basics of GF technology and its main applications with future prospects.
High fructose corn syrup (HFCS)-associated health problems have raised concerns. We investigated the effects of HFCS-containing drinking water on body fat, intestinal microbiota structure of mice, and the relationships between them. HFCS drinking water significantly increased body fat content and altered the intestinal microbiome. The Christensenellaceae R-7 group negatively correlated with body weight, perirenal fat, epididymal fat, and liver fat percentage.
The gut microbiome serves as a critical regulator of human physiology. The gut community is influenced by various external factors, mainly diet, pharmaceuticals, stress, exercise, etc. The gut microbiome can be of benefit or harm to the host depending on the metabolites produced. It has been shown that the gut microbiome also plays a significant role on the host metabolism. The alteration of gut microbial composition and reduction of its diversity contribute to the incidence of metabolic diseases. On the other hand, manipulation of gut microbial ecology through balancing some specific types of bacteria or enhancing the number of good bacteria can potentially prevent and serve as a therapeutic approach against metabolic related diseases. This chapter reviews how the gut microbiome interacts with the host, particularly in regulation of metabolism. The involvement of the gut microbiome with the development of metabolic diseases is highlighted. The modulation of the gut microbiome as a target source for prevention of metabolic diseases and possible mechanisms have been reviewed.
A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.
The human gut microbiota harbors a heterogenous and dynamic community of microorganisms which coexist with the host to exert a marked influence on human physiology and health. Throughout the lifespan, diet can shape the composition and diversity of the members of the gut microbiota by determining the microorganisms that will colonize, persist, or become extinct. This is no more pronounced than during early-life succession of the gut microbiome when food type and source changes relatively often and food preferences are established, which is largely determined by geographic location and the customs and cultural practices of that environment. These dietary selection pressures continue throughout life as society has become increasingly mobile and we consume new foods to which we have had no previous exposure. Dietary selection pressures also come in the form of overall reduction or excess such as with the growing problems of food insecurity (lack of food) as well as dietary obesity (overconsumption). These are well-documented forms of dietary selection pressures that have profound impact on the gut microbiota that ultimately may contribute to or worsen disease. However, diets and dietary components can also be used to promote healthy microbial functions in the gut, which will require tailored approaches taking into account an individual’s personal history and doing away with one-size-fits-all nutrition. Herein, we summarize current knowledge on major dietary selection pressures that influence gut microbiota structure and function across and within populations, and discuss both the potential of personalized dietary solutions to health and disease, and the challenges of implementation.
Nonalcoholic fatty liver disease (NAFLD) is one of the major drivers for the rising trend in hepatocellular carcinoma (HCC). Over the past three decades, the incidence of both NAFLD and HCC have increased two- to threefold. It has been forecasted that the number of patients with NAFLD in the Unites States will reach 101 million by 2030; global increase is also foreseen. This trend will likely continue to translate into increased HCC in the Unites States and across the globe. In this chapter, we summarize the current evidence linking NAFLD, metabolic syndrome, particularly obesity and type 2 diabetes mellitus, and HCC. We describe the main molecular mechanisms connecting these metabolic perturbations and hepatocarcinogenesis.
T helper cells are required to produce cytokines adapted to the type of infection. Several subsets have been defined, including pro-inflammatory Th1, Th2, Th17; and anti-inflammatory, Foxp3+ iTreg cells. The fate-determining decision of a naive T cell to differentiate into a defined subset was investigated here.Recent findings showed that metabolic constituents impact T cell differentiation, but so far the influence of glutamine on T cell differentiation has been neglected although being the main source of nitrogen. In this study, deprivation of glutamine induced an abnormal expression of Foxp3 under Th1 but not under Th2 condition, while impairing Th1 and Th17 differentiation. Thus, in poor metabolic micro-environments like solid tumours, a lack of glutamine would initiate a detrimental anti-inflammatory response.A mathematical modelling approach using Ordinary Differential Equations was chosen to capture the properties of T cell differentiation, first in normal conditions with glutamine. In order to train the model, kinetics of the master transcription factors and cytokines expression were measured under different T cell differentiation polarizing conditions. The in vitro data revealed major delays in transcription, translation and secretion of cytokines, which shaped the order of fate decision events. The model could successfully reproduce the dynamics of differentiation, confirming that the 'canonical' differentiation in vitro can be explained by a simple regulatory network. However, it only partially reproduced the plastic behaviour of T cells. The mathematical model will be utilized to compare different mechanistic hypotheses linking glutamine sensing to differentiation.
Type-1 diabetes (T1D) is an autoimmune disease characterized by the loss of immune tolerance to the beta (β)-cells of the pancreas. In this disease, the islet infiltrating immune cells mainly comprising of autoreactive T cells target the β-cell associated antigens, such as preproinsulin (PPI) and in the process destroy β-cells, leading to insulin deficiency. Besides, genetically predisposing human leukocyte antigen (HLA) alleles, several environmental factors have been proposed in the initiation of T1D, as the disease develop years before the actual presentation of clinical symptoms. However, loss of tolerance to β-cells is the central event in the pathogenesis of T1D for which various cellular entities and cellular mechanisms have been implicated. This chapter provides a detailed review of involvement of these cells and mediators, right from the organogenesis of the pancreatic tissue till the destruction of the β-cells. Further, the chapter focuses on the role of various innate immune cells including, macrophages, monocytes, dendritic cells (DCs), neutrophils, natural killer (NK) cells, innate lymphoid cells (ILCs) and adaptive immune cells mainly different subsets of CD4+ and CD8+ T cells and B cells in causing β-cell damage with special focus on immune cells that infiltrate early in the pancreas during the disease process. Amongst the cellular mechanisms, factors such as endoplasmic reticulum (ER) stress and posttranslational modifications (PTM), neutrophil extracellular traps (NETosis), over-expression of major histocompatibility complex (MHC)-I, involvement of major chemokines and inflammatory cytokines have also been discussed. The latter half of the chapter discusses about various immunomodulatory cells, mainly regulatory T cells (Tregs) that are involved in the protection of β-cells and efforts to replace functional β-cells or prevent β-cell destruction. While the complete treatment of T1D is still far in sight, this chapter attempts to refresh the current knowledge on the pathogenesis of the disease from the perspective of cellular players, which might be helpful in exploring newer therapeutic approaches.
An efficient energy harvesting mechanism is likely critical for animals in their natural environment. Intestinal microbiota enriched by a high-fat diet aid in lipid accumulation, a strategy likely evolved for energy harvest in mammals. However, whether this strategy is conserved among vertebrate organisms remains unclear. A bacterial strain (S1), enriched on soybean oil rich medium, was isolated from the gut of Nile tilapia and demonstrated to be a member of the Citrobacter genus. Although a high-fat diet increased the number of Citrobacter spp., these bacteria were not abundant in the intestine by high-throughput sequencing. Addition of bacterium S1 to a high-fat diet modulated intestinal microbial composition and increased high-fat diet-induced lipid accumulation in mesenteric adipose tissue, accompanied by (i) increased triglyceride absorption efficiency and triglyceride reesterification and (ii) increased intestinal permeability. Collectively, our results provide evidence that specific intestinal bacteria aid the host in harvesting more energy from a high-fat diet in fish. Furthermore, the results from the present study also suggest that nondominant bacteria in the gut may play an important role in regulating host metabolism.
IMPORTANCE This study shows that the ability of gut microbiota members to enhance host energy harvest from a high-fat diet is a conserved feature of host-microbe interactions in fish, as in mammals. It also underscores that gut microbiota members are able to significantly impact host biology even when at low abundance.
Okara, the residue of the production of tofu and soybean milk, is rich in dietary fibers (DFs) and phytochemical components such as soy isoflavones (SIs) and soyasaponins (SSs). Despite its nutritive value, okara is scarcely used as a food source as the DFs in okara are mostly insoluble and have adverse effects on food texture. Thus, it is necessary to improve the physicochemical properties of okara. This review presents a detailed investigation on okara food development focusing on nanocellulose (NC) technologies that have progressed in recent years, mainly the Supermasscolloider and Star Burst systems. These NC technologies have increased the dispersion ability, viscosity, and specific surface area of cellulose and okara. Increased viscosity and specific surface area of atomized okara effectively suppressed α-amylase activity, and the increased specific surface area and dispersion ability of okara increased the production of short-chain fatty acids by human dominant gut bacteria. In addition, the consumption of cellulose nanofibrils in conjunction with exercise inhibited the obesity induced by high-fat diets by modulating the gut microbiota balance in mice. Mice experiments indicated that dietary supplementation with SIs and SSs may also have beneficial effects in preventing allergic contact dermatitis, and that the gut microbiota is critical for their therapeutic value. Therefore, frontline technologies for NC will facilitate novel ways to develop healthy foods to prevent obesity and immune-related diseases using okara.
The gut microbiota plays an important role in maintaining human health. Accumulating evidence has indicated an intimate relationship between gut microbiota and cardiovascular diseases (CVD) which has become the leading cause of death worldwide. The alteration of gut microbial composition (gut dysbiosis) has been proven to contribute to atherosclerosis, the basic pathological process of CVD. In addition, the metabolites of gut microbiota have been found to be closely related to the development of CVD. For example, short-chain fatty acids are widely acclaimed beneficial effect against CVD, whereas trimethylamine-N-oxide is considered as a contributing factor in the development of CVD. In this chapter, we mainly discuss the gut microbial metabolite-involved mechanisms of CVD focusing on atherosclerosis, hypertension, diabetes, obesity, and heart failure. Targeting gut microbiota and related metabolites are novel and promising strategies for the treatment of CVD.
Chronic liver injury mainly comprises viral hepatitis, fatty liver disease, autoimmune hepatitis, cirrhosis and liver cancer. It is well established that gut microbiota serves as the key upstream modulator for chronic liver injury progression. Indeed, the term “gut–liver axis” was mostly applied for chronic liver injury. In the current chapter, we will summarize the relationship between gut microbiota and chronic liver injury, including the interaction between them based on latest clinic and basic research.
Despite the fact that there is still insufficient evidence to consider non-alcoholic fatty liver disease (NAFLD) as an stand-alone indication for bariatric surgery, many clinical and histopathological beneficial effects on both NAFLD and non-alcoholic steatohepatitis (NASH) have been shown. Although weight loss seems to be the obvious mechanism, weight-loss independent factors are also believed to be involved. Among them, changes in gut microbiota and bile acids (BA) composition may be playing an unappreciated role in the improvement of NAFLD. In this review we examine the mechanisms and interdependence of the gut microbiota and BA, and their influence on NAFLD pathogenesis and its reversal following bariatric surgery. According to the currently available evidence, gut microbiota has a major influence on BA composition. In fact, both BA and microbiome disturbances (dysbiosis) play a role in the etiopathogenesis of NAFLD and might be potential therapeutic targets. In addition, bariatric surgery can modify the intraluminal ileal environment in a way that causes significant repopulation of the gut microbiota and a reversal of the plasma primary/secondary BA ratio, which, in turn, induces weigh-independent metabolic improvements.
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