德国蒂宾根大学Lisa Maier小组的一项最新研究探明了非抗生素破坏对肠道病原体的定植抗性。2025年7月16日出版的《自然》杂志发表了这项成果。

在这里，小组研究了非抗生素如何影响肠道共生体抵抗肠道病原体定植的能力。该研究团队还开发了一种体外测定法来评估肠道病原体在药物干扰微生物群落中的生长情况。致病性γ变形杆菌比共生菌对非抗生素更耐药，其处理后扩增增强。在测试的53种药物中，28%可促进鼠伤寒沙门氏菌（S. Tm）在合成菌群和人源粪便菌群中的生长，其他肠道病原体也呈现类似趋势。非抗生素通过抑制共生菌的生长、改变微生物间的相互作用和增强S. Tm利用代谢生态位。体外促进病原体扩张的药物增加了肠道S. Tm在小鼠体内的负荷。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的发作，并增加了由S. Tm引导的炎症。他们的研究发现，非抗生素是以前被忽视的可能导致肠道感染的风险因素。

研究人员表示，非抗生素药物可以改变肠道微生物群的组成，但它们对人体健康的影响在很大程度上是未知的。

附：英文原文

Title: Non-antibiotics disrupt colonization resistance against enteropathogens

Author: Griehammer, Anne, de la Cuesta-Zuluaga, Jacobo, Mller, Patrick, Gekeler, Cordula, Homolak, Jan, Chang, Hsuan, Schmitt, Katharina, Planker, Chiara, Schmidtchen, Verena, Gallage, Suchira, Bohn, Erwin, Nguyen, Taylor H., Hetzer, Jenny, Heikenwlder, Mathias, Huang, Kerwyn Casey, Zahir, Taiyeb, Maier, Lisa

Issue&Volume: 2025-07-16

Abstract: Non-antibiotic drugs can alter the composition of the gut microbiome1, but they have largely unknown implications for human health2. Here we examined how non-antibiotics affect the ability of gut commensals to resist colonization by enteropathogens3. 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.

DOI: 10.1038/s41586-025-09217-2

Source: https://www.nature.com/articles/s41586-025-09217-2