Using corticosteroids to reshape the gut microbiome: Implications for inflammatory bowel diseases

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, Eugene B. Chang

Research output: Contribution to journalArticlepeer-review


Background: 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. 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, 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. Results: Exposure 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. Conclusions: Commensal 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.

Original languageEnglish (US)
Pages (from-to)963-972
Number of pages10
JournalInflammatory Bowel Diseases
Issue number5
StatePublished - Mar 3 2015


  • animal models of IBD
  • inflammation in IBD
  • microbiology of IBD
  • steroids in IBD

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology


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