Innovative Institute of Animal Healthy Breeding, College of Animal Science & Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, China.
Laboratory Animal Center of Nanfang Hospital, Southern Medical University, Guangzhou, China.
Front Immunol. 2021 Jan 8;11:583652. doi: 10.3389/fimmu.2020.583652. eCollection 2020.
Several studies have reported an intricate link between the G protein-coupled receptor 109A (GPR109A) and intestinal health. Upon activation, induced by butyric acid and β-hydroxybutyric acid, GPR109A regulates the expression of tight junction proteins, exerts anti-inflammatory effects, and maintains the integrity of the intestinal barrier. However, its function and the mechanism of action in combating the infection caused by exogenous pathogenic microorganisms remain unclear. This study established an animal model of infection by oral enterotoxigenic (ETEC) gavage to examine the underlying mechanism(s) and protective effects of GPR109A on the intestinal tract. Experimental GPR109Aand GPR109A mice were orally administered with 1 × 10 colony-forming units (CFUs) of ETEC, and changes in body weight were then observed. The colonization and translocation of ETEC in the intestine were detected by the plate counting method. The expression of tight junction proteins and the levels of inflammatory factors and secretory IgA (SIgA) in the intestine were detected by quantitative real-time polymerase chain reaction (q-PCR), western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The results demonstrated that GPR109Amice were more susceptible to ETEC infection, showing more severe inflammatory reactions and intestinal damage. Moreover, the secretion of IgA in the intestinal tract of GPR109A mice was significantly increased after ETEC infection, whereas the IgA levels in GPR109Amice did not change significantly. We added 5 g/L sodium butyrate to the drinking water of all mice. The GPR109A mice were protected against ETEC infection and no effect was observed in GPR109Amice. Similarly, sodium butyrate increased the SIgA content in the gut of the GPR109A mice and no effect was observed in GPR109Amice. In conclusion, activated GPR109A is effective against the colonization and translocation of ETEC in the gut and maintains the integrity of the intestinal barrier, possibly by promoting the secretion of intestinal IgA.
已有多项研究报道了 G 蛋白偶联受体 109A（GPR109A）与肠道健康之间存在复杂的联系。GPR109A 被丁酸和β-羟基丁酸激活后，可调节紧密连接蛋白的表达，发挥抗炎作用，并维持肠道屏障的完整性。然而，其在抵御外源性致病微生物感染方面的功能和作用机制尚不清楚。本研究通过口服灌胃肠产毒性大肠杆菌（ETEC）建立了感染动物模型，以研究 GPR109A 对肠道的潜在作用机制和保护作用。实验性 GPR109A 和 GPR109A 小鼠口服给予 1×10 菌落形成单位（CFU）的 ETEC，然后观察体重变化。通过平板计数法检测 ETEC 在肠道中的定植和易位。通过定量实时聚合酶链反应（q-PCR）、Western 印迹、酶联免疫吸附测定（ELISA）和免疫组织化学检测紧密连接蛋白的表达以及肠道中炎症因子和分泌型免疫球蛋白 A（SIgA）的水平。结果表明，GPR109A 小鼠更易受到 ETEC 感染，表现出更严重的炎症反应和肠道损伤。此外，ETEC 感染后 GPR109A 小鼠肠道 IgA 的分泌显著增加，而 GPR109A 小鼠的 IgA 水平没有明显变化。我们向所有小鼠饮用水中添加 5 g/L 丁酸钠。GPR109A 小鼠对 ETEC 感染具有保护作用，而 GPR109A 小鼠则没有观察到这种作用。同样，丁酸钠增加了 GPR109A 小鼠肠道中的 SIgA 含量，而 GPR109A 小鼠则没有观察到这种作用。综上所述，激活的 GPR109A 可有效阻止 ETEC 在肠道中的定植和易位，并维持肠道屏障的完整性，可能是通过促进肠道 IgA 的分泌。
