The impacts of individual commensal microbes on immunity and disease can differ dramatically depending on the surrounding microbial context; however, the specific bacterial combinations that dictate divergent immunological outcomes remain largely undefined. Here, we characterize an immunostimulatory Allobaculum species from an inflammatory bowel disease patient that exacerbates colitis in gnotobiotic mice. Allobaculum inversely associates with the taxonomically divergent immunostimulatory species Akkermansia muciniphila in human-microbiota-associated mice and human cohorts. Co-colonization with A. muciniphila ameliorates Allobaculum-induced intestinal epithelial cell activation and colitis in mice, whereas Allobaculum blunts the A.muciniphila-specific systemic antibody response and reprograms the immunological milieu in mesenteric lymph nodes by blocking A.muciniphila-induced dendritic cell activation and T cell expansion. These studies thus identify a pairwise reciprocal interaction between human gut bacteria that dictates divergent immunological outcomes. Furthermore, they establish a generalizable framework to define the contextual cues contributing to the “incomplete penetrance” of microbial impacts on human disease.

个体共生微生物对免疫和疾病的影响可能因周围微生物环境的不同而有很大差异。然而，决定不同免疫学结果的特定细菌组合在很大程度上仍不清楚。在这里，我们描述了来自炎症性肠病患者的免疫刺激性同种杆菌物种，该物种会加剧无菌小鼠的结肠炎。在人类微生物群相关的小鼠和人类群体中，Allobaculum与分类学上不同的免疫刺激物种Akkermansia muciniphila呈负相关。与A. muciniphila共定殖可改善小鼠中异菌诱导的肠上皮细胞活化和结肠炎，而Allobaculum通过阻断A.muciniphila诱导的树突细胞活化和 T 细胞扩增，减弱A.muciniphila特异性全身抗体反应，并重新编程肠系膜淋巴结中的免疫环境。因此，这些研究确定了人类肠道细菌之间的成对相互作用，这种相互作用决定了不同的免疫学结果。此外，他们建立了一个通用框架来定义导致微生物对人类疾病影响“不完全外显”的背景线索。