Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA, USA.
Cell Host Microbe. 2024 Oct 9;32(10):1774-1786.e9. doi: 10.1016/j.chom.2024.07.025. Epub 2024 Aug 23.
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.
肠道微生物群防止有害微生物进入体内，这一功能被称为定植抗力。肠病原体沙门氏菌血清型（S.）伤寒通过其毒力因子通过未知机制破坏定植抵抗力。使用代谢物分析和遗传分析，我们表明，腔内病原体丰度的最初增加是由有氧呼吸和简单糖（如葡萄糖）的混合酸发酵共同驱动的，这导致它们从代谢组中耗尽。粪便中病原体丰度的最初增加与盲肠中乙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，这些宿主环境的变化先于微生物群落组成的变化。我们得出结论，即使在肠道微生物群落没有明显组成变化的情况下，宿主环境的变化也会削弱定植抵抗力。
