TY - JOUR AB - Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that 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 a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-α while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2−/−) mice showed a distinctly “leaky” gut physiology coupled with upregulation 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 that involves luminal sensing and signaling by TLR4. AU - Venkatesh,M AU - Mukherjee,S AU - Wang,H AU - Li,H AU - Sun,K AU - Benechet,AP AU - Qiu,Z AU - Maher,L AU - Redinbo,MR AU - Phillips,RS AU - Fleet,JC AU - Kortagere,S AU - Mukherjee,P AU - Fasano,A AU - Le,Ven J AU - Nicholson,JK AU - Dumas,ME AU - Khanna,KM AU - Mani,S DO - 10.1016/j.immuni.2014.06.014 EP - 310 PY - 2014/// SN - 1074-7613 SP - 296 TI - Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the Xenobiotic sensor PXR and toll-like receptor 4 T2 - Immunity UR - http://dx.doi.org/10.1016/j.immuni.2014.06.014 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000341455300016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202 UR - https://www.sciencedirect.com/science/article/pii/S1074761314002362?via%3Dihub VL - 41 ER -