{"doi":"10.17615/a268-h719","title":"Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4","abstract":"Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is as a ligand for PXR in vivo, and IPA down-regulated enterocyte TNF–α while up-regulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2−/−) mice showed a distinctly “leaky” gut physiology coupled with up-regulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2−/−Tlr4−/− mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway which involves luminal sensing and signaling by TLR4.","journal":"Carolina Digital Repository (University of North Carolina at Chapel Hill)","year":2020,"id":140075,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9478,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":604323,"name":"Subhajit Mukherjee","orcid":null,"position":1,"is_corresponding":false},{"id":603645,"name":"Hongwei Wang","orcid":"0000-0003-2868-5112","position":2,"is_corresponding":false},{"id":367067,"name":"Zhijuan Qiu","orcid":"0000-0003-3097-7181","position":3,"is_corresponding":false},{"id":236183,"name":"Sridhar Mani","orcid":"0000-0003-4132-6157","position":4,"is_corresponding":false},{"id":342625,"name":"Katherine Sun","orcid":"0000-0003-1493-5512","position":5,"is_corresponding":false},{"id":371186,"name":"James C. Fleet","orcid":"0000-0002-0142-9517","position":6,"is_corresponding":false},{"id":75650,"name":"Kamal M. Khanna","orcid":"0000-0002-9328-3817","position":7,"is_corresponding":false},{"id":604324,"name":"Jessica Le Ven","orcid":null,"position":8,"is_corresponding":false},{"id":302126,"name":"Jeremy K. Nicholson","orcid":"0000-0002-8123-8349","position":9,"is_corresponding":false},{"id":603646,"name":"Alexandre P. Bénéchet","orcid":"0000-0001-8746-2459","position":10,"is_corresponding":false},{"id":603647,"name":"Hao Li","orcid":"0000-0003-2832-4851","position":11,"is_corresponding":false},{"id":546858,"name":"Paromita Mukherjee","orcid":"0000-0001-5121-6280","position":12,"is_corresponding":false},{"id":604325,"name":"Phillips, Robert S.","orcid":null,"position":13,"is_corresponding":false},{"id":84271,"name":"Marc‐Emmanuel Dumas","orcid":"0000-0001-9523-7024","position":14,"is_corresponding":false},{"id":603648,"name":"Leigh Maher","orcid":"0000-0002-1103-9811","position":15,"is_corresponding":false},{"id":36347,"name":"Matthew R. Redinbo","orcid":"0000-0003-0814-5346","position":16,"is_corresponding":false},{"id":342627,"name":"Sandhya Kortagere","orcid":"0000-0002-3532-8669","position":17,"is_corresponding":false},{"id":547564,"name":"Madhukumar Venkatesh","orcid":null,"position":18,"is_corresponding":false},{"id":227641,"name":"Alessio Fasano","orcid":"0000-0002-2134-0261","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:13.583586Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}