The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms. Using metabolite profiling and genetic analysis, we show that the initial rise in luminal pathogen abundance was powered by a combination of aerobic respiration and mixed acid fermentation of simple sugars, such as glucose, which resulted in their depletion from the metabolome. The initial rise in the abundance of the pathogen in the feces coincided with a reduction in the cecal concentrations of acetate and butyrate and an increase in epithelial oxygenation. Notably, these changes in the host environment preceded changes in the microbiota composition. We conclude that changes in the host environment can weaken colonization resistance even in the absence of overt compositional changes in the gut microbiota.

肠道微生物群可以防止有害微生物进入体内，这种功能称为定植抵抗。肠道病原体鼠伤寒沙门氏菌利用其毒力因子通过未知机制打破定植抗性。通过代谢物分析和遗传分析，我们发现管腔病原体丰度的最初上升是由有氧呼吸和单糖（例如葡萄糖）的混合酸发酵相结合推动的，这导致了它们从代谢组中的消耗。粪便中病原体丰度的最初上升与盲肠中醋酸盐和丁酸盐浓度的降低以及上皮氧合作用的增加同时发生。值得注意的是，宿主环境的这些变化先于微生物群组成的变化。我们的结论是，即使肠道微生物群没有明显的组成变化，宿主环境的变化也会削弱定植抵抗力。