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This study aimed to comprehensively examine crosstalk between mucosal gene expression and microbiota in patients with IBD. To study tissue-specific interactions, we perform transcriptomic (RNA-seq) and microbial (16S-rRNA-seq) profiling of 697 intestinal biopsies (645 derived from 335 patients with IBD and 52 from 16 non-IBD controls). Mucosal gene expression patterns in IBD are mainly determined by tissue location and inflammation, whereas the mucosal microbiota composition shows a high degree of individual specificity. Analysis of transcript-bacteria interactions identifies six distinct groups of inflammation-related pathways that are associated with intestinal microbiota (adjusted\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). An increased abundance of\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    is associated with higher expression of genes involved in fatty acid metabolism, while\n                    <jats:italic>Bacteroides<\/jats:italic>\n                    correlates with increased metallothionein signaling. In patients with fibrostenosis, a transcriptional network dominated by immunoregulatory genes is associated with\n                    <jats:italic>Lachnoclostridium<\/jats:italic>\n                    bacteria in non-stenotic tissue (adjusted\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05), while being absent in CD without fibrostenosis. In patients using TNF-\u03b1-antagonists, a transcriptional network dominated by fatty acid metabolism genes is linked to\n                    <jats:italic>Ruminococcaceae<\/jats:italic>\n                    (adjusted\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). Mucosal microbiota composition correlates with enrichment of intestinal epithelial cells, macrophages, and NK-cells. Overall, these data demonstrate the presence of context-specific mucosal host-microbe interactions in IBD, revealing significantly altered inflammation-associated gene-taxa modules, particularly in patients with fibrostenotic CD and patients using TNF-\u03b1-antagonists. This study provides compelling insights into host\u2013microbe interactions that may guide microbiota-directed precision medicine and fuels the rationale for microbiota-targeted therapeutics as a strategy to alter disease course in IBD.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-45855-2","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T07:02:15Z","timestamp":1708153335000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Mucosal host-microbe interactions associate with clinical phenotypes in inflammatory bowel disease"],"prefix":"10.1038","volume":"15","author":[{"given":"Shixian","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5754-3821","authenticated-orcid":false,"given":"Arno R.","family":"Bourgonje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2119-0539","authenticated-orcid":false,"given":"Ranko","family":"Gacesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadien H.","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes R.","family":"Bj\u00f6rk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6422-4343","authenticated-orcid":false,"given":"Amber","family":"Bangma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwan J.","family":"Hidding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik M.","family":"van Dullemen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijn C.","family":"Visschedijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaas Nico","family":"Faber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4563-7462","authenticated-orcid":false,"given":"Gerard","family":"Dijkstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2725-6148","authenticated-orcid":false,"given":"Hermie J. 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