An <i>Aeromonas</i> variant that produces aerolysin promotes susceptibility to ulcerative colitis
Zhihui Jiang, Ye Wang, Jianfeng Gong, Xin Chen, Dong Hang, Caiping Chen, Hong Xin, Junhao Zhang, Kehui Qiu, Yang Liao, Pengpeng Li, Han Wang, Zhuoxin Yang, Tiantian Qiu, Yuwei Zhou, Zexu Chen, Hairong Zhou, Xinqi Shan, N. Zhou, Lutao Liu, Fan Feng, Feng Su, Hui Ma, Zhifeng Liu, Wei He, Lei Fang, Ji Xuan, Zhenji Gan, Xia Gao, Jian Zhang, Huaqun Chen, Fangyu Wang, Xuena Zhang, Min‐Sheng Zhu
Abstract
Ulcerative colitis (UC) is a severe inflammatory bowel disease affecting millions of people worldwide, but the factors driving the condition are poorly understood. In tissue samples from individuals with UC, we found that macrophages were depleted from areas of the colon that did not yet exhibit overt epithelial inflammation. We hypothesized that toxins produced by bacteria could impair macrophages and that this could promote wider inflammation. We isolated a variant of Aeromonas genus from stool samples from UC patients, which we termed macrophage-toxic bacteria (MTB), because aerolysin secreted by MTB caused macrophage death. MTB colonized mice under pathogenic conditions and triggered colitis. Antibodies against aerolysin alleviated colitis induced by Aeromonas in mice. In a cohort, UC patients more frequently tested positive for Aeromonas than healthy controls did.