During Salmonella-induced gastroenteritis, mucosal inflammation creates a niche that favors the expansion of the pathogen population over the microbiota. Here, we show that Salmonella Typhimurium infection was accompanied by dysbiosis, decreased butyrate levels, and substantially elevated lactate levels in the gut lumen. Administration of a lactate dehydrogenase inhibitor blunted lactate production in germ-free mice, suggesting that lactate was predominantly of host origin. Depletion of butyrate-producing Clostridia, either through oral antibiotic treatment or as part of the pathogen-induced dysbiosis, triggered a switch in host cells from oxidative metabolism to lactate fermentation, increasing both lactate levels and Salmonella lactate utilization. Administration of tributyrin or a PPARγ agonist diminished host lactate production and abrogated the fitness advantage conferred on Salmonella by lactate utilization. We conclude that alterations of the gut microbiota, specifically a depletion of Clostridia, reprogram host metabolism to perform lactate fermentation, thus supporting Salmonella infection.

在沙门氏菌引起的肠胃炎期间，黏膜炎症创造了一个有利于病原体种群扩张超过微生物群的生态位。在这里，我们发现鼠伤寒沙门氏菌感染伴随着肠道菌群失调、丁酸盐水平降低和肠道内乳酸水平显着升高。乳酸脱氢酶抑制剂的施用减弱了无菌小鼠中乳酸的产生，表明乳酸主要来源于宿主。通过口服抗生素治疗或作为病原体诱导的生态失调的一部分，产生丁酸盐的梭菌的消耗引发宿主细胞从氧化代谢到乳酸发酵的转变，增加了乳酸水平和沙门氏菌乳酸利用。施用三丁酸甘油酯或 PPARγ 激动剂减少了宿主乳酸的产生，并消除了乳酸利用赋予沙门氏菌的适应性优势。我们得出结论，肠道微生物群的改变，特别是梭状芽胞杆菌的消耗，重新编程宿主代谢以进行乳酸发酵，从而支持沙门氏菌感染。