2. Academic Validation
  3. An Aeromonas variant that produces aerolysin promotes susceptibility to ulcerative colitis

An Aeromonas variant that produces aerolysin promotes susceptibility to ulcerative colitis

  • Science. 2025 Nov 20;390(6775):eadz4712. doi: 10.1126/science.adz4712.
Zhihui Jiang # 1,  Ye Wang # 1,  Jianfeng Gong # 2,  Xin Chen # 1,  Dong Hang 3,  Caiping Chen 4,  Xin Hong 5,  Junhao Zhang 1,  Kehui Qiu 1,  Yang Liao 1,  Pengpeng Li 1,  Han Wang 1,  Zhuoxin Yang 2,  Tiantian Qiu 1,  Yuwei Zhou 1,  Zexu Chen 1,  Hairong Zhou 5,  Xinqi Shan 6,  Na Zhou 6,  Lutao Liu 6,  Fan Feng 7,  Feng Su 8,  Hongfeng Ma 9,  Zhifeng Liu 10,  Weiqi He 11,  Lei Fang 1,  Ji Xuan 2,  Zhenji Gan 1,  Xia Gao 1,  Jian Zhang 12,  Huaqun Chen 6,  Fangyu Wang 2,  Xuena Zhang 1 8 13,  Minsheng Zhu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, National Resource Center for Mutant Mice, Department of Gastroenterology of Nanjing Drum Tower Hospital, and Suqian Scientific Research Institute, Medical School of Nanjing University, Nanjing, China.
  • 2 Department of Gastroenterology and Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
  • 3 Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
  • 4 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • 5 Department of Non-Communicable Disease Prevention, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China.
  • 6 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
  • 7 Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • 8 Department of Gastroenterology, Affiliated Suqian Hospital of Xuzhou Medical University, Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian, China.
  • 9 Department of Rehabilitation Medicine, Huzhou Rehabilitation Hospital, Huzhou, China.
  • 10 Children's Hospital of Nanjing Medical University, Nanjing, China.
  • 11 Department of Gastroenterology, Children's Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Cambridge-Suda Genomic Resource Center, Soochow Medical College of Soochow University, Suzhou, China.
  • 12 State Key Laboratory for Conservation and Utilization of Bio-Resources, School of Life Sciences, Center for Life Sciences, Yunnan University, Kunming, China.
  • 13 Jinling Pharmaceutical, Nanjing, China.
  • # Contributed equally.
PMID: 41264716 DOI: 10.1126/science.adz4712
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.

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