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.Peer reviewe

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

Intestinal Ralstonia pickettii augments glucose intolerance in obesity

An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.Peer reviewe

Quantifying diet-induced metabolic changes of the human gut microbiome

The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome-scale is a useful tool to decipher microbe-microbe, diet-microbe and microbe-host interactions. Here, we describe the CASINO (Community and Systems-level Interactive Optimization) toolbox, a comprehensive computational platform for analysis of microbial communities through metabolic modeling. We first validated the toolbox by simulating and testing the performance of single bacteria and whole communities in in vitro. Focusing on metabolic interactions between the diet, gut microbiota and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight individuals, and validated our predictions by fecal and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention

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: NCT0242755

Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling.

Dietary lipids may influence the abundance of circulating inflammatory microbial factors. Hence, inflammation in white adipose tissue (WAT) induced by dietary lipids may be partly dependent on their interaction with the gut microbiota. Here, we show that mice fed lard for 11 weeks have increased Toll-like receptor (TLR) activation and WAT inflammation and reduced insulin sensitivity compared with mice fed fish oil and that phenotypic differences between the dietary groups can be partly attributed to differences in microbiota composition. Trif(-/-) and Myd88(-/-) mice are protected against lard-induced WAT inflammation and impaired insulin sensitivity. Experiments in germ-free mice show that an interaction between gut microbiota and saturated lipids promotes WAT inflammation independent of adiposity. Finally, we demonstrate that the chemokine CCL2 contributes to microbiota-induced WAT inflammation in lard-fed mice. These results indicate that gut microbiota exacerbates metabolic inflammation through TLR signaling upon challenge with a diet rich in saturated lipids

Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis

International audienceBeneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN. Thus, microbiota-produced succinate is a previously unsuspected bacterial metabolite improving glycemic control through activation of IGN

Early Life Microbiota : Impact of Delivery Mode and Infant Feeding

The microbial community that reside in or pass through our intestine is known as gut microbiota. The birth of a baby is not only a start of a new human life, but also a start of a whole new microbial ecosystem. The assembly of the gut microbiota begins at birth with colonization by microbes from the biosphere. Environmental factors drive the assembly of the gut microbiota in early life and have been linked to health outcomes later in life. This article will describe the impact of delivery mode and infant feeding on the establishment, development and maturation of the infant gut microbiota