• Edmond Y Huang, Takuya Inoue, Vanessa A Leone, Sushila Dalal, Ketrija Touw, Yunwei Wang, Mark W Musch, Betty Theriault, Kazuhide Higuchi, Sharon Donovan, Jack Gilbert, and Eugene B Chang.
• *Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois; †2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan; ‡Department of Surgery, University of Chicago, Chicago, Illinois; §Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois; ‖Biosciences Division, Argonne National Laboratory, Argonne, Illinois; ¶Department of Ecology and Evolution, University of Chicago, Chicago, Illinois; **Marine Biological Laboratory, Woods Hole, Massachusetts; and ††College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, China.
• Inflamm. Bowel Dis. 2015 May 1; 21 (5): 963-72.

BackgroundCommensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. We sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation.MethodsAdult male C57Bl/6 mice, germ-free, Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for 4 weeks. Fecal samples were collected for gut microbiota analysis through 16S rRNA terminal restriction fragment length polymorphism and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. Germ-free mice were conventionalized with gut microbes from treated and nontreated groups to determine their functional capacities in recipient hosts.ResultsExposure to dexamethasone in wild-type mice led to substantial shifts in gut microbiota over a 4-week period. Furthermore, a significant downregulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a proinflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pretreated with dexamethasone, however, ameliorated symptoms of inflammation.ConclusionsCommensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after glucocorticoid exposure. These findings underscore the notion that intestinal microbes comprise a "microbial organ" essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.

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