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

Content Provider	Springer Nature : BioMed Central
Author	Foley, Sage E. Tuohy, Christine Dunford, Merran Grey, Michael J. De Luca, Heidi Cawley, Caitlin Szabady, Rose L. Maldonado-Contreras, Ana Houghton, Jean Marie Ward, Doyle V. Mrsny, Randall J. McCormick, Beth A.
Abstract	Background 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. Results We have identified a “functional core” microbiome of the intestinal gut community, specifically genera within the Clostridia and Bacilli classes, that is necessary and sufficient for P-gp induction in the intestinal epithelium in mouse models. Metagenomic analysis of this core microbial community revealed that short-chain fatty acid and secondary bile acid production positively associate with P-gp expression. We have further shown these two classes of microbiota-derived metabolites synergistically upregulate P-gp expression and function in vitro and in vivo. Moreover, in patients suffering from ulcerative colitis (UC), we find diminished P-gp expression coupled to the reduction of epithelial-derived anti-inflammatory endocannabinoids and luminal content (e.g., microbes or their metabolites) with a reduced capability to induce P-gp expression. Conclusion Overall, by means of both in vitro and in vivo studies as well as human subject sample analysis, we identify a mechanistic link between cooperative functional outputs of the complex microbial community and modulation of P-gp, an epithelial component, that functions to suppress overactive inflammation to maintain intestinal homeostasis. Hence, our data support a new cross-talk paradigm in microbiome regulation of mucosal inflammation. Video abstract
Related Links	https://microbiomejournal.biomedcentral.com/counter/pdf/10.1186/s40168-021-01137-3.pdf
Ending Page	17
Page Count	17
Starting Page	1
File Format	HTM / HTML
ISSN	20492618
DOI	10.1186/s40168-021-01137-3
Journal	Microbiome
Issue Number	1
Volume Number	9
Language	English
Publisher	BioMed Central
Publisher Date	2021-09-07
Access Restriction	Open
Subject Keyword	Medical Microbiology Bioinformatics Microbial Ecology Microbiology Microbial Genetics and Genomics Virology P-glycoprotein Multi-drug resistance transporter Endocannabinoid Inflammatory bowel diseases Ulcerative colitis Inflammation Intestinal epithelium Short-chain fatty acids Secondary bile acids Microbiome
Content Type	Text
Resource Type	Article
Subject	Microbiology Microbiology (medical)
Journal Impact Factor	13.8/2023
5-Year Journal Impact Factor	17.9/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

The diet rapidly and differentially affects the gut microbiota and host lipid mediators in a healthy population

Probiotic Cocktail Alleviates Intestinal Inflammation Through Improving Gut Microbiota and Metabolites in Colitis Mice

Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates the severity of DSS colitis

The negative effect of Akkermansia muciniphila-mediated post-antibiotic reconstitution of the gut microbiota on the development of colitis-associated colorectal cancer in mice

Interplay of gut microbiota and host epithelial mitochondrial dysfunction is necessary for the development of spontaneous intestinal inflammation in mice

The Emerging Role of Bile Acids in the Pathogenesis of Inflammatory Bowel Disease

Fecal microbiota and bile acids in IBD patients undergoing screening for colorectal cancer

A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways

Bile Acids: Key Players in Inflammatory Bowel Diseases?

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

Similar Documents

The diet rapidly and differentially affects the gut microbiota and host lipid mediators in a healthy population

Probiotic Cocktail Alleviates Intestinal Inflammation Through Improving Gut Microbiota and Metabolites in Colitis Mice

Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates the severity of DSS colitis

The negative effect of Akkermansia muciniphila-mediated post-antibiotic reconstitution of the gut microbiota on the development of colitis-associated colorectal cancer in mice

Interplay of gut microbiota and host epithelial mitochondrial dysfunction is necessary for the development of spontaneous intestinal inflammation in mice

The Emerging Role of Bile Acids in the Pathogenesis of Inflammatory Bowel Disease

Fecal microbiota and bile acids in IBD patients undergoing screening for colorectal cancer

A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways

Bile Acids: Key Players in Inflammatory Bowel Diseases?

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