Chicken colibacillosis is caused by avian pathogenic Escherichia coli (APEC), and results in huge economic losses to the poultry industry. With the investigation of the gut-lung axis, more studies have demonstrated the important role of gut microbiota in lung inflammation. The precise role of the gut microbiota in chickens-associated colibacillosis, however, is unknown. Thus, this study assessed the function of the gut microbiota in the chicken defense against APEC infection. Chicken gut microbiota was depleted by drinking water with a mixture of antibiotics (Abx), and subsequently, a model of colibacillosis was established by the intranasal perfusion of APEC. The results showed that gut microbiota protects the chicken challenge by APEC from aggravated lung histopathologic injury, up-regulated pro-inflammatory cytokine production, and increased bacterial load in lung tissues compared with controls. In addition, the air-blood barrier permeability was significantly increased in gut microbiota-depleted chickens compared to the control chickens after challenge with APEC. Furthermore, feeding acetate significantly inhibited the lung inflammatory response and the reduced air-blood permeability induced by APEC infection. The expression of free fatty acid receptor 2 (FFAR2), a receptor for acetate, was also increased in the lung after treatment with acetate. In conclusion, depletion of the gut microbiota resulted in increased susceptibility of chickens to APEC challenge, and gut microbiota derived acetate acted as a protective mediator during the APEC challenge. Novel therapeutic targets that focus on the gut microbiota may be effective in controlling colibacillosis in poultry.

鸡大肠杆菌病是由禽致病性大肠杆菌引起的（APEC），给家禽业造成巨大的经济损失。随着对肠-肺轴的研究，越来越多的研究证明了肠道菌群在肺部炎症中的重要作用。然而，肠道微生物群在鸡相关大肠杆菌病中的确切作用尚不清楚。因此，本研究评估了肠道微生物群在鸡抵御 APEC 感染中的功能。通过饮用含有抗生素混合物 (Abx) 的水，鸡肠道微生物群被耗尽，随后，通过 APEC 的鼻内灌注建立了大肠杆菌病模型。结果表明，与对照组相比，肠道微生物群保护 APEC 攻击鸡免受肺组织病理学损伤加重、促炎细胞因子产生上调和肺组织细菌负荷增加。此外，在用 APEC 攻击后，与对照鸡相比，肠道微生物群耗尽鸡的气血屏障通透性显着增加。此外，喂食醋酸盐显着抑制了 APEC 感染引起的肺部炎症反应和空气-血液渗透性降低。游离脂肪酸受体 2 (FFAR2)（一种乙酸盐受体）在用乙酸盐治疗后在肺中的表达也增加。总之，肠道微生物群的耗竭导致鸡对 APEC 攻击的易感性增加，并且肠道微生物群衍生的醋酸盐在 APEC 攻击期间充当保护介质。专注于肠道微生物群的新治疗靶点可能有效控制家禽的大肠杆菌病。