Fishbein Skye R S, DeVeaux Anna L, Khanna Sakshi, Ferreiro Aura L, Liao James, Agee Wesley, Ning Jie, Mahmud Bejan, Wallace Miranda J, Hink Tiffany, Reske Kimberly A, Cass Candice, Guruge Janaki, Leekha Sidh, Rengarajan Sunaina, Dubberke Erik R, Dantas Gautam
The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA.
The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
Cell Host Microbe. 2025 Jan 8;33(1):30-41.e6. doi: 10.1016/j.chom.2024.12.002. Epub 2024 Dec 27.
Gastrointestinal colonization by Clostridioides difficile is common in healthcare settings and ranges in presentation from asymptomatic carriage to lethal C. difficile infection (CDI). We used a systems biology approach to investigate why patients colonized with C. difficile have a range of clinical outcomes. Microbiota humanization of germ-free mice with fecal samples from toxigenic C. difficile carriers revealed a spectrum of virulence among clinically prevalent clade 1 lineages and identified candidate taxa, including Blautia, as markers of stable colonization. Using gnotobiotic mice engrafted with defined human microbiota, we validated strain-specific CDI severity across clade 1 strains isolated from patients. Mice engrafted with a community broadly representative of colonized patients were protected from severe disease across all strains without suppression of C. difficile colonization. These results underline the capacity of gut community structure to attenuate a diversity of pathogenic strains without inhibiting colonization, providing insight into determinants of stable C. difficile carriage.
艰难梭菌在医疗机构中的胃肠道定植很常见，其表现范围从无症状携带到致命的艰难梭菌感染（CDI）。我们采用系统生物学方法来研究为什么感染艰难梭菌的患者会有一系列临床结果。用来自产毒艰难梭菌携带者的粪便样本对无菌小鼠进行微生物群人源化，揭示了临床流行的1型谱系中存在一系列毒力，并确定了包括布劳特氏菌属在内的候选分类群作为稳定定植的标志物。使用植入特定人类微生物群的悉生小鼠，我们验证了从患者分离出的1型菌株中菌株特异性CDI的严重程度。植入广泛代表定植患者群落的小鼠在所有菌株中都能免受严重疾病的侵害，而不会抑制艰难梭菌的定植。这些结果强调了肠道群落结构在不抑制定植的情况下减弱多种致病菌株的能力，为艰难梭菌稳定携带的决定因素提供了见解。
