{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:24:21Z","timestamp":1786947861375,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The gut microbiome mediates the reductive catabolism of bilirubin into urobilinoids, yet the bacteria and enzymes responsible for the later steps of this pathway remain largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we combine untargeted UPLC\/HRMS metabolomics with shotgun metagenomic sequencing of fecal samples from 119 participants, including patients with Crohn\u2019s disease, ulcerative colitis, and healthy controls, to map disruptions in the bilirubin catabolic pathway in inflammatory bowel disease (IBD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We show that stercobilinogen and stercobilin, the terminal metabolites of this pathway, are depleted (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01) in IBD patients irrespective of disease subtype, while upstream intermediates, D-urobilinogen, remain unchanged. This metabolic bottleneck coincides with a marked reduction in members of the\n                      <jats:italic>Lachnospiraceae<\/jats:italic>\n                      family, specifically\n                      <jats:italic>Blautia<\/jats:italic>\n                      sp. SG-772 and three uncharacterized species, which show strong positive correlations with stercobilinogen and stercobilin levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings implicate\n                      <jats:italic>Lachnospiraceae<\/jats:italic>\n                      as key mediators of the yet unknown enzymatic conversion of I-urobilinogen to stercobilinogen, extending the family\u2019s known metabolic repertoire beyond short-chain fatty acid production. Given that bilirubin and its reduced metabolite stercobilinogen possess antioxidant properties, their depletion may contribute to the oxidative burden in the IBD gut. Conversely, the concurrent elevation of D-urobilin, which lacks these protective properties and has been linked to metabolic dysfunction in other contexts, may further exacerbate inflammation. Our results identify fecal bilirubin metabolites as candidate biomarkers of microbial dysbiosis in IBD and nominate specific\n                      <jats:italic>Lachnospiraceae<\/jats:italic>\n                      taxa for functional characterization of the missing stercobilinogen reductase.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1871609","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:26:11Z","timestamp":1786944371000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Disrupted terminal bilirubin catabolism links Lachnospiraceae depletion to inflammatory bowel disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Omer","family":"Sabti","sequence":"first","affiliation":[{"name":"Department of Chemistry, Ben Gurion University of the Negev","place":["Be\u2019er Sheva, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ksenia","family":"Lialin-Tzadikov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ben Gurion University of the Negev","place":["Be\u2019er Sheva, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Department of Systems Immunology, Weizmann Institute of Science","place":["Rehovot, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mally","family":"Dori-Bachash","sequence":"additional","affiliation":[{"name":"Department of Systems Immunology, Weizmann Institute of Science","place":["Rehovot, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaked","family":"Uzi-Gavrilov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ben Gurion University of the Negev","place":["Be\u2019er Sheva, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohar","family":"Tik","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ben Gurion University of the Negev","place":["Be\u2019er Sheva, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roi","family":"Mashiach","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ben Gurion University of the Negev","place":["Be\u2019er Sheva, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvah","family":"Zorea","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Ben Gurion University of the Negev","place":["Be\u2019er Sheva, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itzhak","family":"Mizrahi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Ben Gurion University of the Negev","place":["Be\u2019er Sheva, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arik","family":"Segal","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Soroka University Medical Center","place":["Be\u2019er Sheva, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keren","family":"Moyal-Attias","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Soroka University Medical Center","place":["Be\u2019er Sheva, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eran","family":"Elinav","sequence":"additional","affiliation":[{"name":"Department of Systems Immunology, Weizmann Institute of Science","place":["Rehovot, Israel"]},{"name":"Division of Microbiome and Cancer, German Cancer Research Center (DKFZ)","place":["Heidelberg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Meijler","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ben Gurion University of the Negev","place":["Be\u2019er Sheva, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1010853","DOI":"10.3389\/fcimb.2022.1010853","article-title":"The oral-gut axis: Salivary and fecal microbiome dysbiosis in patients with inflammatory bowel disease.","volume":"12","author":"Abdelbary","year":"2022","journal-title":"Front. 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