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  3. Clostridium butyricum-induced balance in colonic retinol metabolism and short-chain fatty acid levels inhibit IgA-related mucosal immunity and relieve colitis developments

Clostridium butyricum-induced balance in colonic retinol metabolism and short-chain fatty acid levels inhibit IgA-related mucosal immunity and relieve colitis developments

  • Microbiol Res. 2025 Sep:298:128203. doi: 10.1016/j.micres.2025.128203.
Jing Xu 1,  Haoming Xu 2,  Jianhong Li 1,  Wenqi Huang 3,  Yingfei Li 2,  Xue Guo 1,  Minzheng Zhu 1,  Yao Peng 4,  Youlian Zhou 5,  Yuqiang Nie 6
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, China; Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China.
  • 2 Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China.
  • 3 Division of Rheumatology, Department of Medicine/Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
  • 4 Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. Electronic address: pennysmail@126.com.
  • 5 Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. Electronic address: eyyoulianzhou@scut.edu.cn.
  • 6 Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. Electronic address: eynieyuqiang@scut.edu.cn.
PMID: 40319662 DOI: 10.1016/j.micres.2025.128203
Abstract

Gut microbiota and their metabolites play a significant role in inflammatory bowel disease. Here, we attempted to determine the anti-inflammatory role of the probiotic Clostridium. butyricum (CB) in inflammatory bowel disease and identify the exact immune mechanism. The clinical significance of Clostridiales and CB was explored in patients with ulcerative colitis. The inflammation-suppressive role of CB was evaluated in mice with DSS-induced colitis. 16S rRNA Sequencing was performed to assess changes in the gut microbiota. Altered transcription levels were detected by RNA Sequencing. Flow cytometry was performed to assess the frequency of IgA responses to gut microbiota. Clostridiales and CB were depleted in ulcerative colitis. Oral gavage with CB significantly suppressed weight loss and colon shortening in the dextran sulfate sodium-induced colitis mouse model. Intestinal barrier injury was reversed and the gut microbiota was restored upon treatment with CB administration. The mucosal immune response to gut microbiota was reversed upon treatment with CB. CB conditional medium was more effective than heat-killed CB in alleviating inflammation. Mechanistically, retinol metabolism and retinoic acid levels were higher in groups treated with CB and butyrate. CB and the metabolite butyrate exerted a suppressive role on the abundance of Immunoglobulin A-coated gut microbiota by inhibiting retinoic acid synthesis. In summary, CB protects against inflammation and intestinal barrier injury by producing anti-inflammatory metabolites that can regulate the mucosal immune response to gut microbiota by increasing retinoic acid levels in the colon.

Keywords

Butyrate; Clostridiales; Clostridium. butyricum; Immunoglobulin A-coated bacteria; Retinoic acid.

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