Elucidating the role of Campylobacter concisus-derived indole metabolites in gut inflammation and immune modulation

• 成果类型: Article
• 署名作者: Park, Jong - Duk; Lee, Seoung Rak; Dhennezel, Catherine; Taylor, Noel; Dame, Andrea; Kadoki, Motohiko; Pishchany, Gleb; Graham, Daniel B.; Xavier, Ramnik J.; Seyedsayamdost, Mohammad R.
• 署名单位: Princeton University; Pusan National University; Pusan National University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Princeton University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10531
• DOI: 10.1073/pnas.2514071122
• 发表日期: 2025-08-26
• 关键词: vivo; term

摘要

The gut microbiota plays a pivotal role in maintaining human health with dysbiosis linked to a variety of diseases. Metagenome sequencing and robust statistical analysis have linked specific strains, including the gut bacterium Campylobacter concisus, to Crohn's disease and ulcerative colitis, together known as inflammatory bowel disease (IBD). However, the roles of this and other strains in disease progression remain to be investigated. Herein, we assess the contribution of C. concisus secondary metabolites to inflammation. Through untargeted metabolomics, we identified a diverse array of previously isolated from a marine bacterium. Collectively, these metabolites modulate inflammatory responses by significantly inducing the release of proinflammatory aromatic hydrocarbon receptor arylhydrocarbon receptor and in vivo intravital imaging revealed a marked increase in the recruitment and activation of immune cells, specifically neutrophils and macrophages, following the administration of trisindoline. Several indole metabolites also exhibited antimicrobial activity against commensal strains that facilitate a proper immune response. Our study provides a possible rationale for the association of C. concisus with IBD and underscores the complex interplay between gut as key modulators of inflammation offers new avenues for therapeutic intervention.