Grießhammer Anne, de la Cuesta-Zuluaga Jacobo, Müller Patrick, Gekeler Cordula, Homolak Jan, Chang Hsuan, Schmitt Katharina, Planker Chiara, Schmidtchen Verena, Gallage Suchira, Bohn Erwin, Nguyen Taylor H, Hetzer Jenny, Heikenwälder Mathias, Huang Kerwyn Casey, Zahir Taiyeb, Maier Lisa
Interfaculty Institute for Microbiology and Infection Medicine Tübingen, University of Tübingen, Tübingen, Germany.
Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, University of Tübingen, Tübingen, Germany.
Nature. 2025 Jul 16. doi: 10.1038/s41586-025-09217-2.
Non-antibiotic drugs can alter the composition of the gut microbiome, but they have largely unknown implications for human health. Here we examined how non-antibiotics affect the ability of gut commensals to resist colonization by enteropathogens. We also developed an in vitro assay to assess enteropathogen growth in drug-perturbed microbial communities. Pathogenic Gammaproteobacteria were more resistant to non-antibiotics than commensals and their post-treatment expansion was potentiated. For 28% of the 53 drugs tested, the growth of Salmonella enterica subsp. enterica serovar Typhimurium. (S. Tm) in synthetic and human stool-derived communities was increased, and similar effects were observed for other enteropathogens. Non-antibiotics promoted pathogen proliferation by inhibiting the growth of commensals, altering microbial interactions and enhancing the ability of S. Tm to exploit metabolic niches. Drugs that promoted pathogen expansion in vitro increased the intestinal S. Tm load in mice. For the antihistamine terfenadine, drug-induced disruption of colonization resistance accelerated disease onset and increased inflammation caused by S. Tm. Our findings identify non-antibiotics as previously overlooked risk factors that may contribute to the development of enteric infections.
非抗生素药物可改变肠道微生物群的组成，但它们对人类健康的影响在很大程度上尚不清楚。在这里，我们研究了非抗生素如何影响肠道共生菌抵抗肠道病原体定植的能力。我们还开发了一种体外试验，以评估药物干扰的微生物群落中肠道病原体的生长情况。致病性γ-变形菌比共生菌对非抗生素更具抗性，且它们在治疗后的扩张得到增强。在所测试的53种药物中，有28%会使合成和人粪便来源群落中的肠炎沙门氏菌亚种肠炎血清型鼠伤寒沙门氏菌（S. Tm）的生长增加，其他肠道病原体也观察到类似效果。非抗生素通过抑制共生菌的生长、改变微生物相互作用以及增强鼠伤寒沙门氏菌利用代谢生态位的能力来促进病原体增殖。在体外促进病原体扩张的药物会增加小鼠肠道中的鼠伤寒沙门氏菌载量。对于抗组胺药特非那定，药物诱导的定植抗性破坏加速了疾病发作，并增加了由鼠伤寒沙门氏菌引起的炎症。我们的研究结果表明，非抗生素是以前被忽视的可能导致肠道感染发生的风险因素。
