GPR35-mediated kynurenic acid sensing contributes to maintenance of gut microbiota homeostasis in ulcerative colitis.

Ulcerative colitis (UC) is a recurrent inflammatory disease related to gut microbiota disorder. Metabolites and their sensors play an important role in the communication between gut microbes and their host. Our previous study revealed that G protein-coupled receptor 35 (GPR35) is a key guardian of kynurenic acid (KA) and a core element of the defense responses against gut damage. However, the mechanism remains unknown. In this study, a DSS-induced rat colitis model was established and 16S rRNA sequencing was applied to explore the influence of GPR35-mediated KA sensing on gut microbiota homeostasis. Our results demonstrated that GPR35-mediated KA sensing is a necessary component in maintaining gut barrier integrity against DSS-induced damage. Furthermore, we provide compelling evidence suggesting that GPR35-mediated KA sensing plays a crucial role in maintaining gut microbiota homeostasis, which contributes to alleviation of DSS-induced colitis. In addition, five classes (Actinobacteria, Beta-/Gamma-proteobacteria, Erysipelotrichi, and Coriobacteriia) and six genera (Corynebacterium, Allobaculum, Parabacteroides, Sutterella, Shigella, and Xenorhabdus) were identified as the marked bacterial taxa that characterized the progression and outcome of colitis and are regulated by GPR35-mediated KA sensing. Our findings highlight that GPR35-mediated KA sensing is an essential defense mechanism against disorder of gut microbiota in UC. The results provide insights into the key role of specific metabolites and their monitor in maintaining gut homeostasis.