Browsing by Subject "Gut"
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Item Temporal Modulation of Gut Microbiome and Metabolome by Morphine(2015-12) Wang, FuyuanOpioids such as morphine have many beneficial properties as analgesics, however, opioids may induce multiple adverse gastrointestinal symptoms. It has been recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. However, it is unclear how opioids modulate gut homeostasis. A mouse model was used to investigate the effects of morphine treatment on gut microbiome and metabolome. When phylogenetic profiles of gut microbes were characterized, the results revealed a significant shift in the colonic microbiome following morphine treatment when compared to placebo. At the species level, Enterococcus faecalis was associated with morphine-modulated gut microbiome alteration. Morphine treatment also resulted in dramatic changes in the fecal metabolomic profile. Through LC-MS based metabolomics profiling analysis, fatty acids and bile acids metabolism and in particular, deoxycholic acid (DCA) and phosphatidylethanolamines (PEs) was identified to be greatly affected by morphine treatment, implicating that changes in the microbiome community has functional consequences. In a longitudinal study, naltrexone, an opioid receptor antagonist, reversed the effect of morphine on bile acid metabolism, indicating morphine induced changes are opioid receptor dependent. Cross-correlation between gut microbiome and metabolome indicated association between bacterial communities and functional metabolites. Furthermore, morphine induced dysbiosis disrupts morphine metabolism and its enterohepatic recirculation. This study shed light on the effects of morphine on the microbiome-metabolome-host axis, and its role in gut homeostasis. In a mouse model of Citrobacter rodentium infection, morphine treatment resulted in 1) the promotion of C. rodentium systemic dissemination, 2) increase in virulence factors expression with C. rodentium colonization in intestinal contents, 3) altered gut microbiome, 4) damaged integrity of gut epithelial barrier function, 5) inhibition of C. rodentium-induced increase of goblet cells, and 6) dysregulated IL-17A immune response. This is the first study to demonstrate that morphine promotes pathogen dissemination in the context of intestinal C. rodentium infection, indicating morphine modulates virulence factor-mediated adhesion of pathogenic bacteria and induces disruption of mucosal host defense during C. rodentium intestinal infection in mice.Item Wild Primate Gut Microbiota Protect Against Obesity(2017-04) Sidiropoulos, Dimitrios, N; Clayton, Jonathan; Al-Ghalith, Gabe; Shields-Cutler, Robin; Ward, Tonya; Blekhman, Ran; Kashyap, Purna; Knights, DanThe gastrointestinal tract hosts trillions of bacteria that play major roles in metabolism, immune system development, and pathogen resistance. Although there is increasing evidence that low dietary fiber in Westernized societies is associated with dramatic loss of natural human gut microbiome diversity, the role of this loss in obesity and inflammation is not well understood. Non-human primates (NHPs) can be used as model systems for studying the effects of diet and lifestyle disruption on the human gut microbiome. Captive primates are typically exposed to low-fiber diets and tend to have human-associated microbiota in place of their native microbiota. In order to explore interactions between the gut microbiota and dietary fiber, we transplanted captive and wild primate gut microbiota into germ-free mice and then exposed them to either a high- or low-fiber diet. We found that the group receiving low-fiber diet and captive primate microbiota became obese and had high levels of circulating inflammatory cytokines, while mice receiving high-fiber diet and wild primate microbiota remained healthy. Mice with the wild primate microbiota and low-fiber diet acquired intermediate levels of obesity, demonstrating an interaction between dietary fiber and the microbiota. These results show that the modern human gut microbiome interacts with low-fiber diets to cause inflammation and obesity, and suggest a possible clinical role for manipulation of the microbiota in the treatment of obesity.