Intact Gut Microbiota Research Articles

Selective colonization ability of human fecal microbes in different mouse gut environments.

Mammalian hosts constantly interact with diverse exogenous microbes, but only a subset of the microbes manage to colonize due to selective colonization resistance exerted by host genetic factors as well as the native microbiota of the host. An important question in microbial ecology and medical science is if such colonization resistance can discriminate closely related microbial species, or even closely related strains of the same species. Using human-mouse fecal microbiota transplantation and metagenomic shotgun sequencing, we reconstructed colonization patterns of human fecal microbes in mice with different genotypes (C57BL6/J vs. NSG) and with or without an intact gut microbiota. We found that mouse genotypes and the native mouse gut microbiota both exerted different selective pressures on exogenous colonizers: human fecal Bacteroides successfully established in the mice gut, however, different species of Bacteroides selectively enriched under different gut conditions, potentially due to a multitude of functional differences, ranging from versatility in nutrient acquisition to stress responses. Additionally, different clades of Bacteroides cellulosilyticus strains were selectively enriched in different gut conditions, suggesting that the fitness of conspecific microbial strains in a novel host environment could differ.

An intact gut microbiota may be required for lactoferrin-driven immunomodulation in rats

Lactoferrin can modulate both the host immunity and gut microbiota. However, whether the immune modulation requires the gut microbiota has not been directly shown. Thus, our study compared (1) lactoferrin-driven immunomodulation profiles and (2) changes in fecal phylogenic metagenome with and without antibiotics-induced dysbiosis in rats. Rats receiving only lactoferrin but not both lactoferrin and antibiotics had a Th-1 type cytokine serum profile. Significant differences were detected between the fecal microbiota of the lactoferrin and control groups at day 19 and/or day 33 but not initially, with a shift in the major contributors for community dissimilarity to Clostridium, Lactobacillus, and Oscillibacter valericigenes. The antibiotics-induced dysbiosis enriched the proinflammatory phyla, Proteobacteria and Deferribacteres, together with the anti-inflammatory species, Akkermansia muciniphila, while suppressed some butyrate-producers from the Firmicutes phylum. Our study shows that an intact microbiota is necessary for lactoferrin-driven immunomodulation.

Potential contributions of gut microbiota to the nutrition of the detritivorous sesarmid crab Parasesarma erythodactyla

Mangrove leaf litter, the dominant food of the detritivorous sesarmid crab Parasesarma erythodactyla, is highly deficient in nitrogen and long-chain polyunsaturated fatty acids. We experimentally investigated potential contributions of the gut microbiota to the nutrition of P. erythodactyla by providing crabs with 13C- and 15N-labelled substrates that could lead to biosynthesis of key amino acids and fatty acids. Antibiotic treatment suppressed the gut microbiota of the crabs by reducing bacteria density to 9 and 52 % of those in the non-treated crabs in the amino acid and fatty acid experiments, respectively. Compound-specific isotopic analysis revealed significant 13C-enrichments in threonine (Thr), isoleucine (Ile), phenylalanine (Phe), and docosahexaenoic acid (DHA) in crabs fed 13C-enriched glucose and palmitic acid, respectively, suggesting that these essential nutrients were de novo synthesized in the crab. Antibiotic treatment affected the incorporation of 13C-label to Thr, suggesting an involvement of the gut microbes in the biosynthesis of this amino acid. On the contrary, levels of 13C-enrichment in Ile, Phe, and DHA in crabs with intact and suppressed gut microbiota were comparable, suggesting that these compounds may be synthesized endogenously by the crab. Differences between crabs with and without an intact gut microbiota, however, may have been undetectable because of the high variability in 13C-enrichment of these compounds and the incomplete removal of gut micro-organisms in the antibiotic-treated crabs. Genetic and biochemical capacities enabling the gut microbes to de novo synthesize Ile, Phe, and DHA, therefore, need to be verified by additional approaches.

Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization.

Candida albicans colonization is required for invasive disease1-3. Unlike humans, adult mice with mature intact gut microbiota are resistant to C. albicans gastrointestinal (GI) colonization2,4. But the factors that promote C. albicans colonization resistance are unknown. Here we demonstrate that commensal anaerobic bacteria – specifically Clostridial Firmicutes (Clusters IV and XIVa) and Bacteroidetes – are critical for maintaining C. albicans colonization resistance in mice. Using Bacteroides thetaiotamicron as a model organism, we find that HIF-1α, a transcription factor important for activating innate immune effectors, and the antimicrobial peptide LL37-CRAMP are key determinants of C. albicans colonization resistance. While antibiotic treatment enables C. albicans colonization, pharmacologic activation of colonic Hif1a induces CRAMP expression and results in a significant reduction of C. albicans GI colonization and a 50% decrease in mortality from invasive disease. In the setting of antibiotics, Hif1a and Cramp are required for B. thetaiotamicron-induced protection against CA colonization of the gut. Thus, C. albicans GI colonization modulation by activation of gut mucosal immune effectors may represent a novel therapeutic approach for preventing invasive fungal disease in humans.

Microbial sensing by goblet cells controls immune surveillance of luminal antigens in the colon.

The delivery of luminal substances across the intestinal epithelium to the immune system is a critical event in immune surveillance resulting in tolerance to dietary antigens and immunity to pathogens. How this process is regulated is largely unknown. Recently goblet cell associated passages (GAPs) were identified as a pathway delivering luminal antigens to underlying lamina propria (LP) dendritic cells (DCs) in the steady state. Here we demonstrate that goblet cells (GCs) form GAPs in response to acetycholine (ACh) acting on muscarinic acetylcholine receptor (mAChR) 4. GAP formation in the small intestine (SI) was regulated at the level of ACh production, as GCs rapidly formed GAPs in response to ACh analogues. In contrast, colonic GAP formation was regulated at the level of GC responsiveness to ACh. Myd88 dependent microbial sensing by colonic GCs inhibited the ability of colonic GCs to respond to Ach to form GAPs and deliver luminal antigens to colonic LP-antigen presenting cells (APCs). Disruption of GC microbial sensing opened colonic GAPs and resulted in recruitment of neutrophils and APCs and production of inflammatory cytokines. Thus GC intrinsic sensing of the microbiota plays a critical role regulating the exposure of the colonic immune system to luminal substances.