Gut Microbiota Metabolic Activity Research Articles

The Research Progress on the Interaction between Mammalian Gut Microbiota and the Host's Metabolism Homeostasis during Hibernation.

Hibernating mammals confront seasonal and harsh environmental shifts, prompting a cycle of pre-hibernation feeding and subsequent winter fasting. These adaptive practices induce diverse physiological adjustments within the animal's body. With the gut microbiota's metabolic activity being heavily reliant on the host's diet, this cycle's primary impact is on this microbial community. When the structure and composition of the gut microbiota changes, corresponding alterations in the interactions occur between these microorganisms and their host. These successive adaptations significantly contribute to the host's capacity to sustain relatively stable metabolic and immune functions in severe environmental conditions. A thorough investigation into the reciprocal interplay between the host and gut microbiota during hibernation-induced adaptive changes holds promise for unveiling new insights. Understanding the underlying mechanisms driving these interactions may potentially unlock innovative approaches to address extreme pathological conditions in humans.

Guar Gum-Induced Changes in Gut Microbiota Metabolic Activity and Intestinal Immune Response Augments Susceptibility to Experimental Colitis

ObjectivesGuar gum is a common food additive found in many processed foods. Both preclinical and clinical studies documented the beneficial effect of guar gum on gastrointestinal health. We, therefore, hypothesized that guar gum might attenuate the severity of ulcerative colitis (UC), an inflammatory bowel disease (IBD) that chiefly affects the large intestine.MethodsTo test the effect of guar gum on colitis, wild-type (WT) mice were fed diets containing either cellulose (insoluble fiber as control) or guar gum (soluble fiber, 7.5% w/w) for four weeks. Acute and chronic colitis was induced via epithelial injury [dextran sulfate sodium (DSS, 1.4% w/v) in drinking water for 7 days] or immune hyperactivation [IL-10 receptor neutralization by weekly injections of αIL-10R mAb (1 mg/mouse, intraperitoneally) for 4 weeks], respectively. Colitis development was examined by serological, biochemical, histological, and immunological parameters.ResultsUnexpectedly, experimental mice maintained on a guar gum-containing diet (GuD) exhibited increased susceptibility to both acute and chronic colitis. Relative to the control group, GuD-fed mice experienced greater occurrence of rectal bleeding, diarrhea, splenomegaly, and displayed higher levels of pro-inflammatory markers [serum amyloid A (SAA) and lipocalin 2 (Lcn2)]. Analysis of the composition of gut microbiota and their metabolites revealed elevated branched chain amino acids and reduced butyrate in the GuD-fed groups compared to control, among other differences in gut microbiota community structure. Depletion of gut microbiota with broad spectrum antibiotics reversed colitis susceptibility, suggesting that GuD-induced alterations in gut microbiota might contribute to the severity of experimental colitis. Besides differences in gut microbiota activity, a substantial decrease in colonic IL-18 production (>3 folds) was observed in mice fed GuD. Remarkably, supplementation of recombinant IL-18 (rIL-18) alleviated colitis in GuD-fed mice, suggesting that reduced colonic IL-18 upon GuD feeding increases susceptibility to colitis.ConclusionsCollectively, our study demonstrates that food additive guar gum adversely impacts the gut microbiota activity and colonic immune response and increases susceptibility to colonic inflammation.Funding SourcesCrohn's & Colitis Foundation.

DOP008 Dietary manipulation of the healthy human and colitic murine gut microbiome by CD-TREAT diet and exclusive enteral nutrition; a proof of concept study

Background: The extensive modulation of gut microbiome in children with Crohn's disease (CD) treated with exclusive enteral nutrition (EEN) offers clues about EEN's potential mode of action; but also on the development of novel therapies through dietary manipulation of the gut microbiota. This proof of concept study compared the effect of a novel “ordinary” food-based diet (CD-TREAT diet) and EEN on healthy human and colitic murine gut microbiota. Methods: A) Healthy adults followed two experimental diets for 7 days with a 15 day wash out period in between; EEN and CD-TREAT, an “ordinary” food diet which has similar nutrient and food ingredient composition to EEN (e.g., fibre, gluten, lactose content and fatty acid composition). Participants were randomly allocated to start with EEN or CD-TREAT first. Fresh faecal and urine samples were collected before and after each dietary intervention and 16s rRNA sequencing, untargeted faecal and urine metabolomics (using LC-MS) were performed; B) 10-month-old HLA-B27 and HLA-B7 trangenic rats received EEN, CD-TREAT diet or regular rat chow for 4 weeks. Faeces were collected at baseline, 1, 2, 3 and 4 weeks post treatment initiation. Gut contents, ileal and colonic tissue were harvested at sacrifice. Disease activity was quantified by blinded histological scores and gut microbiota metabolic activity was measured by faecal short chain fatty acids (SCFA) quantification. Results: A) 100 samples were collected from 25 healthy subjects. During EEN and CD-TREAT gut bacterial community structure (using OTUs) significantly changed after both EEN and CD-TREAT (R2=0.15, R2=0.05, p<0.004) and shifted towards the same direction. EEN's and CD-TREAT's impact on 3% OTU community structures was strongly correlated (Adj R2=0.38, p<2.2e-16). Similarly, untargeted faecal metabolomics revealed a strong correlation between the changes during EEN and CD-TREAT (Pearson's R=0.31, p<10–14)$; B) 100 faecal samples were collected from 12 HLA-B27 and 8 HLA-B7 adult transgenic rats. Both dietary interventions increased the body weight of the HLA-B27 rats (Median %weight change, EEN:+9.2 vs CD-TREAT:+15.7 vs Control:-2.1) and decreased the weight of caecum and colon contents. Faecal concentration of total SCFA, acetic, propionate decreased while iso-butyric and isocaproic increased during both dietary interventions [ΔMedian μmol/g, EEN: −324, −271, −44.8, +4.7, +2.2 vs CD-TREAT: −354, −292, −56.2, +3, +1.5]. Histopathology scores revealed that both dietary interventions benefited moderately ileal but not colonic inflammation. Conclusions: We have developed an “EN composition alike” food based diet which induces similar effects on gut microbiome with EEN. This proof of concept study supports a subsequent pilot trial in people with active CD.

In Vivo Pyro-SIP Assessing Active Gut Microbiota of the Cotton Leafworm, Spodoptera littoralis

The gut microbiota is of crucial importance for the host with considerable metabolic activity. Although great efforts have been made toward characterizing microbial diversity, measuring components' metabolic activity surprisingly hasn't kept pace. Here we combined pyrosequencing of amplified 16S rRNA genes with in vivo stable isotope probing (Pyro-SIP) to unmask metabolically active bacteria in the gut of cotton leafworm (Spodoptera littoralis), a polyphagous insect herbivore that consumes large amounts of plant material in a short time, liberating abundant glucose in the alimentary canal as a most important carbon and energy source for both host and active gut bacteria. With 13C glucose as the trophic link, Pyro-SIP revealed that a relatively simple but distinctive gut microbiota co-developed with the host, both metabolic activity and composition shifting throughout larval stages. Pantoea, Citrobacter and Clostridium were particularly active in early-instar, likely the core functional populations linked to nutritional upgrading. Enterococcus was the single predominant genus in the community, and it was essentially stable and metabolically active in the larval lifespan. Based on that Enterococci formed biofilm-like layers on the gut epithelium and that the isolated strains showed antimicrobial properties, Enterococcus may be able to establish a colonization resistance effect in the gut against potentially harmful microbes from outside. Not only does this establish the first in-depth inventory of the gut microbiota of a model organism from the mostly phytophagous Lepidoptera, but this pilot study shows that Pyro-SIP can rapidly gain insight into the gut microbiota's metabolic activity with high resolution and high precision.