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

doi:10.1186/s40168-021-01137-3

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 journal › Article › peer-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 language	English
Article number	183 (2021)
Journal	Microbiome
Volume	9
Early online date	7 Sept 2021
DOIs	https://doi.org/10.1186/s40168-021-01137-3
Publication status	Published - 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

Access to Document

10.1186/s40168-021-01137-3Licence: CC BY

Avance 300 MHz Nuclear Magnetic Resonance (NMR) Spectrometer (1South)
Material and Chemical Characterisation (MC2)
Facility/equipment: Equipment
UHPLC Maxis QTOF MS coupled to an ultra high-pressure Liquid Chromatography system
Material and Chemical Characterisation (MC2)
Facility/equipment: Equipment

Cite this

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title = "Gut microbiota regulation of P-glycoprotein in the intestinal epithelium in maintenance of homeostasis.",

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.",

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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T1 - Gut microbiota regulation of P-glycoprotein in the intestinal epithelium in maintenance of homeostasis.

AU - Foley, Sage

AU - Tuohy, Christine

AU - Dunford, Merran

AU - Grey, Michael J.

AU - De Luca, Heidi

AU - Cawley, Caitlin

AU - Maldonado-Contreras, Ana

AU - Houghton, Jean Marie

AU - Ward, Doyle V.

AU - Mrsny, Randy

AU - McCormick, Beth A.

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N2 - 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.

AB - 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.

KW - IBD

KW - Microbiome

KW - Inflammation

KW - P-glycoprotein

KW - Endocannabinoid

KW - Metabolites

KW - Inflammatory bowel diseases

KW - Ulcerative Colitis

KW - Multi-drug resistance transporter

KW - Intestinal epithelium

KW - Short-chain fatty acids

KW - Secondary bile acids

U2 - 10.1186/s40168-021-01137-3

DO - 10.1186/s40168-021-01137-3

M3 - Article

SN - 2049-2618

VL - 9

JO - Microbiome

JF - Microbiome

M1 - 183 (2021)

ER -

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

Abstract

Funding

Keywords

Access to Document

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Equipment

Avance 300 MHz Nuclear Magnetic Resonance (NMR) Spectrometer (1South)

UHPLC Maxis QTOF MS coupled to an ultra high-pressure Liquid Chromatography system

Cite this