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Title: Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases

Introduction—Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. Here 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. Methods—Adult male C57Bl/6 mice, germ-free (GF), Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for four weeks. Fecal samples were collected for gut microbiota analysis via 16S rRNA T-RFLP and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. GF mice were conventionalized with gut microbes from treated- and non-treated groups to determine their functional capacities in recipient hosts. Results—Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period. Furthermore, a significant down-regulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a pro-inflammatory 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 (IL10-KO) mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pre-treated with DEX, however, ameliorated symptoms of inflammation.more » We conclude that commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC 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.« less
Authors:
 [1] ;  [2] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [1]
  1. Univ. of Chicago, IL (United States). Knapp Center for Biomedical Discovery, Dept. of Medicine
  2. Osaka Medical College, Takatsuki, Osaka (Japan). 2nd Dept. of Internal Medicine
  3. Univ. of Illinois, Urbana, IL (United States). Dept. of Food Science and Human Nutrition
  4. Argonne National Lab. (ANL), Argonne, IL (United States). Biosciences Division; Univ. of Chicago, IL (United States). Dept. of Ecology and Evolution; Marine Biological Laboratory, Woods Hole, MA (United States); Zhejiang Univ., Hangzhou (China). College of Environmental and Resource Sciences
Publication Date:
OSTI Identifier:
1280876
Grant/Contract Number:
DK-42086; DK097268; T32 DK07074; DK47722; NIDDK UH3DK083993
Type:
Accepted Manuscript
Journal Name:
Inflammatory Bowel Diseases
Additional Journal Information:
Journal Volume: 21; Journal Issue: 5; Journal ID: ISSN 1078-0998
Publisher:
Crohn's & Colitis Foundation of America
Research Org:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org:
USDOE; National Inst. of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES Animal models of IBD; Inflammation in IBD; Microbiology of IBD; Steroids in IBD