Beresford-Jones Benjamin S, Suyama Satoshi, Clare Simon, Soderholm Amelia, Xia Wangmingyu, Sardar Puspendu, Lee Junhee, Harcourt Katherine, Lawley Trevor D, Pedicord Virginia A
Jeffrey Cheah Biomedical Centre, Cambridge Institute of Therapeutic Immunology and Infectious Disease, Cambridge Biomedical Campus, Cambridge, UK.
Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.
Microbiome. 2025 Feb 28;13(1):61. doi: 10.1186/s40168-025-02050-9.
Promoting resistance to enteric pathogen infection is a core function of the gut microbiota; however, many of the specific host-commensal interactions that mediate this protection remain uncharacterised. To address this knowledge gap, we monocolonised germ-free mice with mouse-derived commensal microbes to screen for microbiota-induced resistance to Salmonella Typhimurium infection.
We identified Enterocloster clostridioformis as a protective species against S. Typhimurium infection. E. clostridioformis selectively upregulates resistin-like molecule β and cell cycle pathway expression at the level of caecal epithelial cells and increases T-regulatory cells in the underlying mucosal immune system, potentially contributing to reduced infection-induced pathology.
We highlight novel mechanisms of host-microbe interactions that can mediate microbiota-induced resistance to acute salmonellosis. In the backdrop of increasing antibiotic resistance, this study identifies novel potential avenues for further research into protective host responses against enteric infections and could lead to new therapeutic approaches. Video Abstract.
促进对肠道病原体感染的抵抗力是肠道微生物群的核心功能；然而，介导这种保护作用的许多特定宿主与共生菌之间的相互作用仍未得到充分表征。为了填补这一知识空白，我们用源自小鼠的共生微生物对无菌小鼠进行单菌定植，以筛选微生物群诱导的对鼠伤寒沙门氏菌感染的抵抗力。
我们鉴定出梭状芽胞杆菌样肠球菌是一种抵抗鼠伤寒沙门氏菌感染的保护性物种。梭状芽胞杆菌样肠球菌在盲肠上皮细胞水平选择性地上调抵抗素样分子β和细胞周期途径的表达，并增加下层黏膜免疫系统中的调节性T细胞，这可能有助于减轻感染引起的病理变化。
我们强调了宿主-微生物相互作用的新机制，这些机制可以介导微生物群诱导的对急性沙门氏菌病的抵抗力。在抗生素耐药性不断增加的背景下，本研究确定了进一步研究宿主对肠道感染的保护性反应的新的潜在途径，并可能带来新的治疗方法。视频摘要。
