From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites.

A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease.

Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits.

Soluble dietary fibers promote metabolic benefits on body weight and glucose control, but underlying mechanisms are poorly understood. Recent evidence indicates that intestinal gluconeogenesis (IGN) has beneficial effects on glucose and energy homeostasis. Here, we show that the short-chain fatty acids (SCFAs) propionate and butyrate, which are generated by fermentation of soluble fiber by the gut microbiota, activate IGN via complementary mechanisms. Butyrate activates IGN gene expression through a cAMP-dependent mechanism, while propionate, itself a substrate of IGN, activates IGN gene expression via a gut-brain neural circuit involving the fatty acid receptor FFAR3. The metabolic benefits on body weight and glucose control induced by SCFAs or dietary fiber in normal mice are absent in mice deficient for IGN, despite similar modifications in gut microbiota composition. Thus, the regulation of IGN is necessary for the metabolic benefits associated with SCFAs and soluble fiber.

FXR is a molecular target for the effects of vertical sleeve gastrectomy.

Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at present the most effective therapy for the treatment of obesity, and are associated with considerable improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering the potential to reveal new targets for therapeutic intervention. Substantial changes in circulating total bile acids are known to occur after VSG. Moreover, bile acids are known to regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor, also known as NR1H4). We therefore examined the results of VSG surgery applied to mice with diet-induced obesity and targeted genetic disruption of FXR. Here we demonstrate that the therapeutic value of VSG does not result from mechanical restriction imposed by a smaller stomach. Rather, VSG is associated with increased circulating bile acids, and associated changes to gut microbial communities. Moreover, in the absence of FXR, the ability of VSG to reduce body weight and improve glucose tolerance is substantially reduced. These results point to bile acids and FXR signalling as an important molecular underpinning for the beneficial effects of this weight-loss surgery.

Integrated Metabolomics and Lipidomics Analyses Reveal Metabolic Reprogramming in Human Glioma with IDH1 Mutation.

Mutations in isocitrate dehydrogenase ( IDH) 1 are high-frequency events in low-grade glioma and secondary glioblastoma, and IDH1 mutant gliomas are vulnerable to interventions. Metabolic reprogramming is a hallmark of cancer. In this study, comprehensive metabolism investigation of clinical IDH1 mutant glioma specimens was performed to explore its specific metabolic reprogramming in real microenvironment. Massive metabolic alterations from glycolysis to lipid metabolism were identified in the IDH1 mutant glioma tissue when compared to IDH1 wild-type glioma. Of note, tricarboxylic acid (TCA) cycle intermediates were in similar levels in both groups, with more pyruvate found entering the TCA cycle in IDH1 mutant glioma. The pool of fatty acyl chains was also reduced, displayed as decreased triglycerides and sphingolipids, although membrane phosphatidyl lipids were not changed. The lower fatty acyl pool may be mediated by the lower protein expression levels of long-chain acyl-CoA synthetase 1 (ACSL1), ACSL4, and very long-chain acyl-CoA synthetase 3 (ACSVL3) in IDH1 mutant glioma. Lower ACSL1 was further found to contribute to the better survival of IDH1 mutant glioma patients based on the The Cancer Genome Atlas (TCGA) RNA sequencing data. Our research provides valuable insights into the tissue metabolism of human IDH1 mutant glioma and unravels new lipid-related targets.

Microbial fermentation of flaxseed fibers modulates the transcriptome of GPR41-expressing enteroendocrine cells and protects mice against diet-induced obesity.

Dietary fibers, an integral part of the human diet, require the enzymatic activity of the gut microbiota for complete metabolism into short-chain fatty acids (SCFAs). SCFAs are important modulators of host metabolism and physiology and act in part as signaling molecules by activating G protein-coupled receptors (GPCRs), such as GPR41. Flaxseed fibers improve metabolism in rodents and mice, but their fermentation profiles, effects on enteroendocrine cells, and associated metabolic benefits are unknown. We fed GPR41-red fluorescent protein mice, an enteroendocrine reporter mouse strain, chow, high-fat diet (HFD), or HFD supplemented either with 10% nonfermentable fiber cellulose or fermentable flaxseed fibers for 12 wk to assess changes in cecal gut microbiota, enteroendocrine cell transcriptome in the ileum and colon, and physiological parameters. We observed that flaxseed fibers restructured the gut microbiota and promoted proliferation of the genera Bifidobacterium and Akkermansia compared with HFD. The shifts in cecal bacterial composition restored levels of the SCFAs butyrate similar to the chow diet, resulting in colonic but not ileal enteroendocrine cell transcriptional changes in genes related to cell cycle, mRNA, and protein transport compared with HFD. Consistent with the effects on enteroendocrine functions, flaxseed fibers also protected mice from diet-induced obesity, potentially by preventing a reduction in energy expenditure induced by an HFD. Our study shows that flaxseed fibers alter cecal microbial ecology, are fermented to SCFAs in the cecum, and modulate enteroendocrine cell transcriptome in the colon, which may contribute to their metabolically favorable phenotype.

Abundance of gut Prevotella at baseline and metabolic response to barley prebiotics.

PURPOSE: We previously showed that short-term intervention with barley kernel bread (BKB) improved glucose tolerance. However, glucose tolerance was not improved in a subset of individuals (non-responders) who were characterized by a low Prevotella/Bacteroides ratio. The purpose of the present study was to investigate if the baseline Prevotella/Bacteroides ratio can be used to stratify metabolic responders and non-responders to barley dietary fiber (DF). METHODS: Fecal samples were collected from 99 healthy humans with BMI < 28 kg/m2 between 50 and 70 years old. The abundance of fecal Prevotella and Bacteroides was quantified with 16S rRNA quantitative PCR. 33 subjects were grouped in three groups: subjects with highest Prevotella/Bacteroides ratios, "HP", n = 12; subjects with lowest Prevotella/Bacteroides ratios, "LP", n = 13; and subjects with high abundance of both measured bacteria, HPB, n = 8. A 3-day randomized crossover intervention with BKB and white wheat bread (control) was performed. Cardiometabolic test variables were analyzed the next day following a standardized breakfast. RESULTS: The BKB intervention lowered the blood glucose responses to the breakfast independently of Prevotella/Bacteroides ratios (P < 0.01). However, independently of intervention, the HP group displayed an overall lower insulin response and lower IL-6 concentrations compared with the LP group (P < 0.05). Furthermore, the groups HP and HPB showed lower hunger sensations compared to the LP group (P < 0.05). CONCLUSIONS: Here we show that the abundance of gut Prevotella and Bacteroides at baseline did not stratify metabolic responders and non-responders to barley DF intervention. However, our results indicate the importance of gut microbiota in host metabolic regulation, further suggesting that higher Prevotella/Bacteroides ratio may be favorable. CLINICALTRIALS. GOV ID: NCT02427555.

Induction of farnesoid X receptor signaling in germ-free mice colonized with a human microbiota.

The gut microbiota influences the development and progression of metabolic diseases partly by metabolism of bile acids (BAs) and modified signaling through the farnesoid X receptor (FXR). In this study, we aimed to determine how the human gut microbiota metabolizes murine BAs and affects FXR signaling in colonized mice. We colonized germ-free mice with cecal content from a mouse donor or feces from a human donor and euthanized the mice after short-term (2 weeks) or long-term (15 weeks) colonization. We analyzed the gut microbiota and BA composition and expression of FXR target genes in ileum and liver. We found that cecal microbiota composition differed between mice colonized with mouse and human microbiota and was stable over time. Human and mouse microbiota reduced total BA levels similarly, but the humanized mice produced less secondary BAs. The human microbiota was able to reduce the levels of tauro-ß-muricholic acid and induce expression of FXR target genes Fgf15 and Shp in ileum after long-term colonization. We show that a human microbiota can change BA composition and induce FXR signaling in colonized mice, but the levels of secondary BAs produced are lower than in mice colonized with a mouse microbiota.

Crosstalk between Bile Acids and Gut Microbiota and Its Impact on Farnesoid X Receptor Signalling.

BACKGROUND: The gut microbiota has a substantial impact on health and disease. The human gut microbiota influences the development and progression of metabolic diseases; however, the underlying mechanisms are not fully understood. The nuclear farnesoid X receptor (FXR), which regulates bile acid homeostasis and glucose and lipid metabolism, is activated by primary human and murine bile acids, chenodeoxycholic acid and cholic acid, while rodent specific primary bile acids tauromuricholic acids antagonise FXR activation. The gut microbiota deconjugates and subsequently metabolises primary bile acids into secondary bile acids in the gut and thereby changes FXR activation and signalling. Key Message: Mouse models have been used to study the crosstalk between bile acids and the gut microbiota, but the substantial differences in bile acid composition between humans and mice need to be considered when interpreting data from such studies and for the development of so-called humanised mouse models. CONCLUSION: It is of special importance to elucidate how a human gut microbiota influences bile acid composition and FXR signalling in colonised mice.

The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis.

The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene (Ffar2) expression is higher in pancreatic islets during pregnancy. Using female Ffar2-/- mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2-/- and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational ß-cell mass, observing that Ffar2-/- mice had diminished gestational expansion of ß-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Together, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis.

Resistant starch intake facilitates weight loss in humans by reshaping the gut microbiota.

Emerging evidence suggests that modulation of gut microbiota by dietary fibre may offer solutions for metabolic disorders. In a randomized placebo-controlled crossover design trial (ChiCTR-TTRCC-13003333) in 37 participants with overweight or obesity, we test whether resistant starch (RS) as a dietary supplement influences obesity-related outcomes. Here, we show that RS supplementation for 8 weeks can help to achieve weight loss (mean -2.8 kg) and improve insulin resistance in individuals with excess body weight. The benefits of RS are associated with changes in gut microbiota composition. Supplementation with Bifidobacterium adolescentis, a species that is markedly associated with the alleviation of obesity in the study participants, protects male mice from diet-induced obesity. Mechanistically, the RS-induced changes in the gut microbiota alter the bile acid profile, reduce inflammation by restoring the intestinal barrier and inhibit lipid absorption. We demonstrate that RS can facilitate weight loss at least partially through B. adolescentis and that the gut microbiota is essential for the action of RS.

Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery.

Roux-en-Y gastric bypass surgery (RYGB) leads to improved glycemic control in individuals with severe obesity beyond the effects of weight loss alone. Here, We addressed the potential contribution of gut microbiota in mediating this favourable surgical outcome by using an established preclinical model of RYGB. 16S rRNA sequencing revealed that RYGB-treated Zucker fatty rats had altered fecal composition of various bacteria at the phylum and species levels, including lower fecal abundance of an unidentified Erysipelotrichaceae species, compared with both sham-operated (Sham) and body weight-matched to RYGB-treated (BWM) rats. Correlation analysis further revealed that fecal abundance of this unidentified Erysipelotrichaceae species linked with multiple indices of glycemic control uniquely in RYGB-treated rats. Sequence alignment of this Erysipelotrichaceae species identified Longibaculum muris to be the most closely related species, and its fecal abundance positively correlated with oral glucose intolerance in RYGB-treated rats. In fecal microbiota transplant experiments, the improved oral glucose tolerance of RYGB-treated compared with BWM rats could partially be transferred to recipient germfree mice, independently of body weight. Unexpectedly, providing L. muris as a supplement to RYGB recipient mice further improved oral glucose tolerance, while administering L. muris alone to chow-fed or Western style diet-challenged conventionally raised mice had minimal metabolic impact. Taken together, our findings provide evidence that the gut microbiota contributes to weight loss-independent improvements in glycemic control after RYGB and demonstrate how correlation of a specific gut microbiota species with a host metabolic trait does not imply causation. IMPORTANCE Metabolic surgery remains the most effective treatment modality for severe obesity and its comorbidities, including type 2 diabetes. Roux-en-Y gastric bypass (RYGB) is a commonly performed type of metabolic surgery that reconfigures gastrointestinal anatomy and profoundly remodels the gut microbiota. While it is clear that RYGB is superior to dieting when it comes to improving glycemic control, the extent to which the gut microbiota contributes to this effect remains untested. In the present study, we uniquely linked fecal Erysipelotrichaceae species, including Longibaculum muris, with indices of glycemic control after RYGB in genetically obese and glucose-intolerant rats. We further show that the weight loss-independent improvements in glycemic control in RYGB-treated rats can be transmitted via their gut microbiota to germfree mice. Our findings provide rare causal evidence that the gut microbiota contributes to the health benefits of metabolic surgery and have implications for the development of gut microbiota-based treatments for type 2 diabetes.

Hypothalamic integrity is necessary for sustained weight loss after bariatric surgery: A prospective, cross-sectional study.

OBJECTIVE: The hypothalamus is the main integrator of peripheral and central signals in the control of energy homeostasis. Its functional relevance for the effectivity of bariatric surgery is not entirely elucidated. Studying the effects of bariatric surgery in patients with hypothalamic damage might provide insight. SUMMARY BACKGROUND DATA: Prospective study to analyze the effects of bariatric surgery in patients with hypothalamic obesity (HO) vs. matched patients with common obesity (CO) with and without bariatric surgery. METHODS: 65 participants were included (HO-surgery: n = 8, HO-control: n = 10, CO-surgery: n = 12, CO-control: n = 12, Lean-control: n = 23). Body weight, levels of anorexic hormones, gut microbiota, as well as subjective well-being/health status, eating behavior, and brain activity (via functional MRI) were evaluated. RESULTS: Patients with HO lost significantly less weight after bariatric surgery than CO-participants (total body weight loss %: 5.5 % vs. 26.2 %, p = 0.0004). After a mixed meal, satiety and abdominal fullness tended to be lowest in HO-surgery and did not correlate with levels of GLP-1 or PYY. Levels of PYY (11,151 ± 1667 pmol/l/h vs. 8099 ± 1235 pmol/l/h, p = 0.028) and GLP-1 (20,975 ± 2893 pmol/l/h vs. 13,060 ± 2357 pmol/l/h, p = 0.009) were significantly higher in the HO-surgery vs. CO-surgery group. Abundance of Enterobacteriaceae and Streptococcus was increased in feces of HO and CO after bariatric surgery. Comparing HO patients with lean-controls revealed an increased activation in insula and cerebellum to viewing high-caloric foods in left insula and cerebellum in fMRI. CONCLUSIONS: Hypothalamic integrity is necessary for the effectiveness of bariatric surgery in humans. Peripheral changes after bariatric surgery are not sufficient to induce satiety and long-term weight loss in patients with hypothalamic damage.

Maturation of the gut metabolome during the first year of life in humans.

The gut microbiota is involved in the production of numerous metabolites that maintain host wellbeing. The assembly of the gut microbiome is highly dynamic, and influenced by many postnatal factors, moreover, little is known about the development of the gut metabolome. We showed that geography has an important influence on the microbiome dynamics in the first year of life based on two independent cohorts from China and Sweden. Major compositional differences since birth were the high relative abundance of Bacteroides in the Swedish cohort and Streptococcus in the Chinese cohort. We analyzed the development of the fecal metabolome in the first year of life in the Chinese cohort. Lipid metabolism, especially acylcarnitines and bile acids, was the most abundant metabolic pathway in the newborn gut. Delivery mode and feeding induced particular differences in the gut metabolome since birth. In contrast to C-section newborns, medium- and long-chain acylcarnitines were abundant at newborn age only in vaginally delivered infants, associated by the presence of bacteria such as Bacteroides vulgatus and Parabacteroides merdae. Our data provide a basis for understanding the maturation of the fecal metabolome and the metabolic role of gut microbiota in infancy.

Curated and harmonized gut microbiome 16S rRNA amplicon data from dietary fiber intervention studies in humans.

Next generation amplicon sequencing has created a plethora of data from human microbiomes. The accessibility to this scientific data and its corresponding metadata is important for its reuse, to allow for new discoveries, verification of published results, and serving as path for reproducibility. Dietary fiber consumption has been associated with a variety of health benefits that are thought to be mediated by gut microbiota. To enable direct comparisons of the response of the gut microbiome to fiber, we obtained 16S rRNA sequencing data and its corresponding metadata from 11 fiber intervention studies for a total of 2,368 samples. We provide curated and pre-processed genetic data and common metadata for comparison across the different studies.

A Continuous Battle for Host-Derived Glycans Between a Mucus Specialist and a Glycan Generalist in vitro and in vivo.

The human gastrointestinal tract is colonized by a diverse microbial community, which plays a crucial role in human health. In the gut, a protective mucus layer that consists of glycan structures separates the bacteria from the host epithelial cells. These host-derived glycans are utilized by bacteria that have adapted to this specific compound in the gastrointestinal tract. Our study investigated the close interaction between two distinct gut microbiota members known to use mucus glycans, the generalist Bacteroides thetaiotaomicron and the specialist Akkermansia muciniphila in vitro and in vivo. The in vitro study, in which mucin was the only nutrient source, indicated that B. thetaiotaomicron significantly upregulated genes coding for Glycoside Hydrolases (GHs) and mucin degradation activity when cultured in the presence of A. muciniphila. Furthermore, B. thetaiotaomicron significantly upregulated the expression of a gene encoding for membrane attack complex/perforin (MACPF) domain in co-culture. The transcriptome analysis also indicated that A. muciniphila was less affected by the environmental changes and was able to sustain its abundance in the presence of B. thetaiotaomicron while increasing the expression of LPS core biosynthesis activity encoding genes (O-antigen ligase, Lipid A and Glycosyl transferases) as well as ABC transporters. Using germ-free mice colonized with B. thetaiotaomicron and/or A. muciniphila, we observed a more general glycan degrading profile in B. thetaiotaomicron while the expression profile of A. muciniphila was not significantly affected when colonizing together, indicating that two different nutritional niches were established in mice gut. Thus, our results indicate that a mucin degrading generalist adapts to its changing environment, depending on available carbohydrates while a mucin degrading specialist adapts by coping with competing microorganism through upregulation of defense related genes.

Decreased Abundance of Akkermansia muciniphila Leads to the Impairment of Insulin Secretion and Glucose Homeostasis in Lean Type 2 Diabetes.

Although obesity occurs in most of the patients with type 2 diabetes (T2D), a fraction of patients with T2D are underweight or have normal weight. Several studies have linked the gut microbiome to obesity and T2D, but the role of gut microbiota in lean individuals with T2D having unique clinical characteristics remains unclear. A metagenomic and targeted metabolomic analysis is conducted in 182 lean and abdominally obese individuals with and without newly diagnosed T2D. The abundance of Akkermansia muciniphila (A. muciniphila) significantly decreases in lean individuals with T2D than without T2D, but not in the comparison of obese individuals with and without T2D. Its abundance correlates inversely with serum 3ß-chenodeoxycholic acid (ßCDCA) levels and positively with insulin secretion and fibroblast growth factor 15/19 (FGF15/19) concentrations. The supplementation with A. muciniphila is sufficient to protect mice against high sucrose-induced impairment of glucose intolerance by decreasing ßCDCA and increasing insulin secretion and FGF15/19. Furthermore, ßCDCA inhibits insulin secretion and FGF15/19 expression. These findings suggest that decreased abundance of A. muciniphila is linked to the impairment of insulin secretion and glucose homeostasis in lean T2D, paving the way for new therapeutic options for the prevention or treatment of diabetes.

Developmental trajectory of the healthy human gut microbiota during the first 5 years of life.

The gut is inhabited by a densely populated ecosystem, the gut microbiota, that is established at birth. However, the succession by which different bacteria are incorporated into the gut microbiota is still relatively unknown. Here, we analyze the microbiota from 471 Swedish children followed from birth to 5 years of age, collecting samples after 4 and 12 months and at 3 and 5 years of age as well as from their mothers at birth using 16S rRNA gene profiling. We also compare their microbiota to an adult Swedish population. Genera follow 4 different colonization patterns during establishment where Methanobrevibacter and Christensenellaceae colonize late and do not reached adult levels at 5 years. These late colonizers correlate with increased alpha diversity in both children and adults. By following the children through age-specific community types, we observe that children have individual dynamics in the gut microbiota development trajectory.

Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals.

Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.

Linking phylogenetic identities of bacteria to starch fermentation in an in vitro model of the large intestine by RNA-based stable isotope probing.

Carbohydrates, including starches, are an important energy source for humans, and are known for their interactions with the microbiota in the digestive tract. Largely, those interactions are thought to promote human health. Using 16S ribosomal RNA (rRNA)-based stable isotope probing (SIP), we identified starch-fermenting bacteria under human colon-like conditions. To the microbiota of the TIM-2 in vitro model of the human colon 7.4 g l(-1) of [U-(13)C]-starch was added. RNA extracted from lumen samples after 0 (control), 2, 4 and 8 h was subjected to density-gradient ultracentrifugation. Terminal-restriction fragment length polymorphism (T-RFLP) fingerprinting and phylogenetic analyses of the labelled and unlabelled 16S rRNA suggested populations related to Ruminococcus bromii, Prevotella spp. and Eubacterium rectale to be involved in starch metabolism. Additionally, 16S rRNA related to that of Bifidobacterium adolescentis was abundant in all analysed fractions. While this might be due to the enrichment of high-GC RNA in high-density fractions, it could also indicate an active role in starch fermentation. Comparison of the T-RFLP fingerprints of experiments performed with labelled and unlabelled starch revealed Ruminococcus bromii as the primary degrader in starch fermentation in the studied model, as it was found to solely predominate in the labelled fractions. LC-MS analyses of the lumen and dialysate samples showed that, for both experiments, starch fermentation primarily yielded acetate, butyrate and propionate. Integration of molecular and metabolite data suggests metabolic cross-feeding in the system, where populations related to Ruminococcus bromii are the primary starch degrader, while those related to Prevotella spp., Bifidobacterium adolescentis and Eubacterium rectale might be further involved in the trophic chain.

Simplified Intestinal Microbiota to Study Microbe-Diet-Host Interactions in a Mouse Model.

The gut microbiota can modulate human metabolism through interactions with macronutrients. However, microbiota-diet-host interactions are difficult to study because bacteria interact in complex food webs in concert with the host, and many of the bacteria are not yet characterized. To reduce the complexity, we colonize mice with a simplified intestinal microbiota (SIM) composed of ten sequenced strains isolated from the human gut with complementing pathways to metabolize dietary fibers. We feed the SIM mice one of three diets (chow [fiber rich], high-fat/high-sucrose, or zero-fat/high-sucrose diets [both low in fiber]) and investigate (1) how dietary fiber, saturated fat, and sucrose affect the abundance and transcriptome of the SIM community, (2) the effect of microbe-diet interactions on circulating metabolites, and (3) how microbiota-diet interactions affect host metabolism. Our SIM model can be used in future studies to help clarify how microbiota-diet interactions contribute to metabolic diseases.