This experiment was conducted to investigate the effect of exposure to high altitude and low oxygen on intestinal microbial communities using mice as an animal model. Fecal microbiota from mice housed in a control environment representing 2,200 meters (NC group) above sea level with 16% Oxygen and mice that were placed in a hypobaric chamber representing 5000 meters (HC group) above sea level with 11% Oxygen for 30 days, were analyzed by the HiSeq Illumina sequencing platform. The results showed a significant difference in beta diversity observed between the two groups, while no significant difference was observed in alpha diversity. Compared with the NC group, the relative abundance of class Epsilonproteobacteria, phlym Actinobacteria, class Erysipelotrichia and genus Helicobacter were significantly lower (P<0.05), while the relative abundance of genus Alistipes was increased in the HC group; Phenotypic analysis showed no significant difference in aerobic, anaerobic, facultatively anaerobic, potentially pathogenic, stress tolerant, mobile element, biofilms formation, gram negative and gram positive between HC group and NC group; Functional analysis results showed significant differences in 34 gene functional metabolic pathways (carbohydrate digestion and absorption, energy metabolism, arachidonic acid metabolism, flavonoid biosynthesis, RIG-I-like receptor signaling pathway, etc) between HC group and NC group. Together, these findings suggest that exposure to high altitude and low oxygen had the potential to change the intestinal microbial communities, which potentially may modulate metabolic processes in mice.

Work from our laboratory and others show that helminth infection attenuates HFD-induced obesity. This current study demonstrates that helminth infection protects against HFD-induced obesity through helminth-induced, Th2dependent alterations of the intestinal microbiota composition and functionality. BACKGROUND & AIMS: Epidemiological and animal studies have indicated an inverse correlation between the rising prevalence of obesity and metabolic syndrome and exposure to helminths. Whether helminth-induced immune response contributes to microbiota remodeling in obesity remains unknown. The aim of this study is to explore the immune-regulatory role of helminth in the prevention of HFD-induced obesity through remodeling gut microbiome. METHODS: C57BL/6J WT and STAT6-/mice were infected with Heligmosomoides polygyrus and followed by high fat diet (HFD) feeding for 6 weeks. The host immune response, body weight, and fecal microbiota composition were analyzed. We used adoptive transfer of M2 macrophages and microbiota transplantation approaches to determine the impact of these factors on HFD-obesity. We also examined stool microbiota composition and short chain fatty acids (SCFAs) concentration and determined the expression of SCFA-relevant receptors in the recipient mice. RESULTS: Helminth infection of STAT6-/-(Th2-deficient) mice and adoptive transfer of helminth-induced alternatively activated (M2) macrophages demonstrated that the helminth-associated Th2 immune response plays an important role in the protection against obesity and induces changes in microbiota composition. Microbiota transplantation showed that helminth-induced, Th2-dependent alterations of the gut microbiota are sufficient to confer protection against obesity. Collectively, these results indicate that helminth infection protects against HFD-induced obesity by Th2-dependent, M2 macrophage-mediated alterations of the intestinal microbiota. CONCLUSION: Our findings provide new mechanistic insights into the complex interplay between helminth infection, the immune system and the gut microbiota in a HFD-induced obesity model and holds promise for gut microbiome-targeted immunotherapy in obesity prevention.

Hyaluronan is a glycosaminoglycan polymer that has been shown to play an important role in homeostasis of the gastrointestinal tract. However, its mechanistic significance in gastrointestinal epithelial barrier elements remain unexplored. Here, our results revealed that hyaluronan treatment resulted in significant changes in the gut microbiota in mice. To demonstrate the functional consequences of hyaluronan-treatment and hyaluronan-induced microbiota alterations, Citrobacter rodentium- and DSS-induced colitis models and microbiota transplantation approaches were utilized. We showed that hyaluronan alleviated intestinal inflammation in both pathogen and chemically induced intestinal mucosal damage. The protection in bacterial colitis was associated with enhanced C. rodentium clearance and alleviation of pathogen-induced gut dysbiosis. Microbiota transplantation experiments showed that the hyaluronan-altered microbiota is sufficient to confer protection against C. rodentium infection. Colonization with Akkermansia muciniphila , a commensal bacterium that is greatly enriched by hyaluronan treatment, alleviated C. rodentium -induced bacterial colitis in mice. Additionally, Akkermansia -induced protection was found to be associated with the induction of goblet cells and the production of mucins and epithelial antimicrobial peptides. Collectively, these results provide novel insights into the regulatory role of hyaluronan in modulating the gut microbiota and immunity in enteric infection and inflammation, with therapeutic potential for gut microbiome-targeted immunotherapy.