ArticleMicrobiome2021
Gut microbiota regulation of P-glycoprotein in the intestinal epithelium in maintenance of homeostasis.
Article in Microbiome, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 112 citations in OpenAlex.
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- Transient receptor potential vanilloid 2 functions as a directional driver for hepoxilin AScience advances · 2026Article
- Metagenomic profiling of gut microbiome in post-cholecystectomy patients with diarrhea: a nested case-control study.BMC microbiology · 2026Article
- Article
- Venous Thromboembolism and Gut Dysbiosis: Mechanistic Links Between Endotoxemia, Microbial Metabolites, and Thromboinflammation.Nutrients · 2026Review
- Multi-omics analysis reveals the association of cesarean delivery with altered gut microbial profiles and a Th2-biased immune response in neonates.Journal of translational medicine · 2026Article
- Shaping death: how the microbiome regulates tumour cell demise and therapy response.Cancer metastasis reviews · 2026Review
- Orchestration of kaempferol nuclear translocation by phase ii metabolic enzymes and efflux transporters suppresses colorectal cancer.PloS one · 2026Article
- Gut Microbiota in the Regulation of Intestinal Drug Transporters: Molecular Mechanisms and Pharmacokinetic Implications.International journal of molecular sciences · 2025Review
- Odoribacter splanchnicus rescues aging-related intestinal P-glycoprotein damage via GDP-L-fucose secretion.Nature communications · 2025Article
- New insights into the effects of microbiome and its derived metabolites on targeted immunotherapy.Journal of the Egyptian National Cancer Institute · 2025Review
- The Role of Micronutrients in Atherosclerosis: Mechanisms and Clinical Application.Journal of cellular and molecular medicine · 2025Review
- Linarin alleviates enterotoxigenic Escherichia coli-induced small intestinal mucosal barrier damage in a piglet model by modulating the gut microbiota.Animal microbiome · 2025Article
- Synbiotics in Alzheimer's disease: mechanisms, clinical evidence, and therapeutic prospects.Journal of translational medicine · 2025Review
- Isochlorogenic Acid C Alleviates Allergic Asthma via Interactions Between Its Bioactive Form and the Gut Microbiome.International journal of molecular sciences · 2025Article
- The Effect of Gut Microbiome Perturbation on the Bioavailability of Glycyrrhizic Acid in Rats.Pharmaceutics · 2025Article
- The interplay between gut bacteria and targeted therapies: implications for future cancer treatments.Molecular medicine (Cambridge, Mass.) · 2025Review
- Succinate-producing microbiota drives tuft cell hyperplasia to protect against Clostridioides difficile.The Journal of experimental medicine · 2025Article
- Identification of Senescence-Related Genes for the Prediction of Ulcerative Colitis Based on Interpretable Machine Learning Models.Journal of inflammation research · 2025Article
- The Oral Microbiota and Its Implications for Inflammatory Bowel Disease: A Literature Review.International journal of general medicine · 2025Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundP-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.
resultsWe 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.
conclusionOverall, 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.