{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:36:48Z","timestamp":1787495808637,"version":"build-2736575974"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"34","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["2023A004123"],"award-info":[{"award-number":["2023A004123"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,8,26]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic toggle=\"yes\">Campylobacter concisus<\/jats:italic>\n                    , to Crohn\u2019s 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\n                    <jats:italic toggle=\"yes\">C. concisus<\/jats:italic>\n                    secondary metabolites to inflammation. Through untargeted metabolomics, we identified a diverse array of nineteen indole-containing metabolites produced by\n                    <jats:italic toggle=\"yes\">C. concisus<\/jats:italic>\n                    , including trisindoline, previously isolated from a marine bacterium. Collectively, these metabolites modulate inflammatory responses by significantly inducing the release of proinflammatory cytokines interleukin (IL)-1\u03b2, IL-6, IL-8, and MCP-1. The metabolites act through the 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\n                    <jats:italic toggle=\"yes\">C. concisus<\/jats:italic>\n                    with IBD and underscores the complex interplay between gut bacteria and host immunity. The identification of indole-derived secondary metabolites as key modulators of inflammation offers new avenues for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2514071122","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T19:00:32Z","timestamp":1755543632000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":11,"title":["Elucidating the role of\n                    <i>Campylobacter concisus<\/i>\n                    \u2013derived indole metabolites in gut inflammation and immune modulation"],"prefix":"10.1073","volume":"122","author":[{"given":"Jong-Duk","family":"Park","sequence":"first","affiliation":[{"name":"Department of Chemistry, Princeton University","place":["Princeton"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8696-2949","authenticated-orcid":false,"given":"Seoung 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