Advanced Science (Aug 2024)
Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2‐VSIR Axis in Glycogen Storage Disease
- Jiaoli Lan,
- Yuxin Zhang,
- Cuiyuan Jin,
- Huan Chen,
- Zexiong Su,
- Jiaxing Wu,
- Ni Ma,
- Xiaoyan Zhang,
- Yiyun Lu,
- Yongxin Chen,
- Xiaolu Zeng,
- Huiqiong Zhang,
- Guilang Zheng,
- Yueyu Sun,
- Chun Wang,
- Yan Hu,
- Yifei Wang,
- Yumei Liu,
- Zhaoyang Zeng,
- Liyun Shi,
- Jun He,
- Aihua Cao,
- Yichao Wang,
- Xu Pan,
- Gulei Jin,
- Ying Wang,
- Xun Jiang,
- Huiqing Shen,
- Qing Tang,
- Xiaoli Xie,
- Yuan Xiao,
- Xuemei Zhong,
- Xuchao Zhang,
- Liang Zeng,
- Liping Ye,
- Jing Xie,
- Lanlan Geng,
- Zhiling Li,
- Xiaohui Wu,
- Ying Wang,
- Ren Mao,
- Shaojun Zhang,
- Siyuan Huang,
- Suling Liu,
- Hanshi Zeng,
- Wanfu Xu,
- Sitang Gong,
- Yuxiong Guo,
- Min Yang
Affiliations
- Jiaoli Lan
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Yuxin Zhang
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Cuiyuan Jin
- Institute of Translational Medicine Zhejiang Shuren University Hangzhou 310015 China
- Huan Chen
- Department of Gastroenterology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 China
- Zexiong Su
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Jiaxing Wu
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Ni Ma
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Xiaoyan Zhang
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Yiyun Lu
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Yongxin Chen
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Xiaolu Zeng
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Huiqiong Zhang
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Guilang Zheng
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Yueyu Sun
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Chun Wang
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Yan Hu
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Yifei Wang
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Yumei Liu
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Zhaoyang Zeng
- Institute of Translational Medicine Zhejiang Shuren University Hangzhou 310015 China
- Liyun Shi
- Institute of Translational Medicine Zhejiang Shuren University Hangzhou 310015 China
- Jun He
- Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University Changsha 410007 China
- Aihua Cao
- Department of Pediatrics Shandong University Qilu Hospital Jinan Shandong 250063 China
- Yichao Wang
- National Health Commission (NHC) Key Laboratory of Birth Defect for Research and Prevention Hunan Provincial Maternal and Child Health Care Hospital Changsha Hunan 410008 China
- Xu Pan
- Department of Basic Medical Sciences School of Medicine Tsinghua University Beijing 100084 China
- Gulei Jin
- Institute of Bioinformatics College of Agronomy and Biotechnology Zhejiang University Hangzhou Zhejiang 277599 China
- Ying Wang
- Division of Pediatric Gastroenterology and Nutrition Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200092 China
- Xun Jiang
- Department of Pediatrics The Second Affiliated Hospital Air Force Military Medical University Xi'an 710032 China
- Huiqing Shen
- Department of gastroenterology Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing 100045 China
- Qing Tang
- Department of Pediatrics The First Affiliated hospital of Guangxi Medical University Nanning 530021 China
- Xiaoli Xie
- Chengdu Women's and Children's Central Hospital School of Medicine University of Electronic Science and Technology of China Chengdu 610073 China
- Yuan Xiao
- Department of Pediatrics Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China
- Xuemei Zhong
- Department of gastroenterology Capital Institute of Pediatrics No. 2 Yabao Road Beijing 100020 China
- Xuchao Zhang
- Guangdong Lung Cancer Institute Medical Research Center Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou 510080 China
- Liang Zeng
- Department of pathology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 China
- Liping Ye
- Department of Gastroenterology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 China
- Jing Xie
- Department of Gastroenterology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 China
- Lanlan Geng
- Department of Gastroenterology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 China
- Zhiling Li
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Xiaohui Wu
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Ying Wang
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Ren Mao
- Department of Gastroenterology The First Affiliated Hospital Sun Yat‐Sen University Guangzhou 510062 China
- Shaojun Zhang
- Research Center of Medical Sciences Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou 510080 China
- Siyuan Huang
- Academy for Advanced Interdisciplinary Studies Peking University Beijing 100091 China
- Suling Liu
- Clinical Laboratory Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou 510080 China
- Hanshi Zeng
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Wanfu Xu
- Department of Gastroenterology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 China
- Sitang Gong
- Department of Gastroenterology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 China
- Yuxiong Guo
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- Min Yang
- Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China
- DOI
- https://doi.org/10.1002/advs.202309471
- Journal volume & issue
-
Vol. 11,
no. 30
pp. n/a – n/a
Abstract
Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.
Keywords