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.
Binbin Dong,Zong Hou,Zhong Zheng,Junpeng Xing,Ningning Zhao,Zhiqiang Liu,Shu Liu
The abundant ginseng neutral polysaccharide (GPN) has been neglected due to its lower activity compared to acidic polysaccharide in ginseng. Herein, the composite enzymes were used to modify the GPN and obtained the enzymatic-degradation-GPN (EGPN). The structural changes were further characterized by GPC, FT-IR, Congo red, XRD, zeta potential, TG, cryo-SEM and AFM. The antioxidant activity of GPNs in vitro was investigated by in vitro chemical experiments and oxidative stress-related indicators on PC12 cells damaged by Aβ 25 – 35 , and EGPN showed favorable antioxidant activity. In addition, EGPN metabolized by intestinal microbiota also significantly increased the viability of injured PC12 cells. Furthermore, in vitro fermentation model was used to investigate the differences of physicochemical properties of GPNs and their regulatory effects on the microbiota. EGPN enhanced the diversity of the microbiota and increased the concentration of short-chain fatty acids (SCFAs). Importantly, EGPN demonstrated a significant reduction in the presence of detrimental bacteria such as Enterococcus and Allobaculum , while simultaneously promoting the growth of beneficial microorganisms including Lactobacillus , Prevotella , and Ruminococcu . This study highlights the potential use of EGPN prepared by composite enzymatic degradation in antioxidant, neuroprotection and restoration of intestinal homeostasis.
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