Gut microbiota regulation of P-glycoprotein in the intestinal epithelium in maintenance of homeostasis.

Sage Foley, Christine Tuohy, Merran Dunford, Michael J. Grey, Heidi De Luca, Caitlin Cawley, Ana Maldonado-Contreras, Jean Marie Houghton, Doyle V. Ward, Randy Mrsny, Beth A. McCormick

Research output: Contribution to journalArticlepeer-review

85 Citations (SciVal)

Abstract

P-glycoprotein (P-gp) plays a critical role in protection of the intestinal epithelia by mediating efflux of drugs/xenobiotics from the intestinal mucosa into the gut lumen. Recent studies bring to light that P-gp also confers a critical link in communication between intestinal mucosal barrier function and the innate immune system. Yet, despite knowledge for over 10 years that P-gp plays a central role in gastrointestinal homeostasis, the precise molecular mechanism that controls its functional expression and regulation remains unclear. Here, we assessed how the intestinal microbiome drives P-gp expression and function.
Original languageEnglish
Article number183 (2021)
JournalMicrobiome
Volume9
Early online date7 Sept 2021
DOIs
Publication statusPublished - 7 Sept 2021

Funding

This work was supported by National Institute of Health grants DK125407, DK109677, and AG67483 to B.A.M; National Institute of Health T32 Training grants S61110000038213, S61110000040758, and T32 AI132152 to S.E.F.; K01DK119414 to M.J.G. We thank Anne Foley and Devon Holler for technical support, and Dr. Randall S. Pellish for method and concept development. We also thank Dr. Yanglan Tan and Dr. Scott Shaffer of the Mass Spectrometry Facility at UMass Medical School for technical support and bile acid analysis. Studies with germ-free mice used services provided by the Harvard Digestive Disease Center (P30DK034854).

Keywords

  • IBD
  • Microbiome
  • Inflammation
  • P-glycoprotein
  • Endocannabinoid
  • Metabolites
  • Inflammatory bowel diseases
  • Ulcerative Colitis
  • Multi-drug resistance transporter
  • Intestinal epithelium
  • Short-chain fatty acids
  • Secondary bile acids

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