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Associations with age-at-disease-onset were specifically analyzed for type 2 diabetes (T2D, low-grade chronic inflammation) and inflammatory bowel disease (IBD, high-grade chronic inflammation) in disease-specific cohorts (FoCus-T2D, <jats:italic>n<\/jats:italic>\u2009=\u2009514; IBD-KC, <jats:italic>n<\/jats:italic>\u2009=\u20091110). Important factors for disease risk were identified using Cox-PH-regression models and time-to-event analysis. We further explored the interaction between identified risk factors and gut microbiome composition using linear models.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Lifestyle factors were clearly linked to disease phenotypes, particularly in T2D and IBD. Still, some factors affected only the age-at-onset, but not disease prevalence. High-quality nutrition significantly delayed onset for both IBD and T2D (IBD: HR\u2009=\u20090.81 [0.66; 0.98]; T2D: HR\u2009=\u20090.45 [0.28; 0.72]). Smoking accelerated T2D onset (HR\u2009=\u20091.82 [1.25; 2.65]) but delayed onset in ulcerative colitis (UC: HR\u2009=\u20090.47 [0.28; 0.79]). Higher microbiota diversity delayed IBD onset (Shannon: HR\u2009=\u20090.58 [0.49; 0.71]) but had no effect on T2D. The abundance of specific microbial genera was strongly associated with various biomedical and lifestyle factors in T2D and IBD. In unaffected controls, these effects were smaller or reversed, potentially indicating a greater susceptibility of the gut microbiome to negative influences in T2D and IBD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The dual insights into age-at-disease-onset and gut microbiota composition in disease emphasize the role of certain biomedical and lifestyle factors, e.g., nutrition quality, in disease prevention and management. Understanding these relationships provides a foundation for developing targeted strategies to mitigate the impact of metabolic and inflammatory diseases through lifestyle modifications and gut health management.\n<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12916-024-03709-0","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T14:03:03Z","timestamp":1729778583000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Metabolic and lifestyle factors accelerate disease onset and alter gut microbiome in inflammatory non-communicable diseases"],"prefix":"10.1186","volume":"22","author":[{"given":"Nathalie","family":"Rohmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Geese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Nestel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Schlicht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Geisler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"T\u00fcrk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fynn","family":"Brix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Jensen-Kroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Demetrowitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Bang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Lieb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik M.","family":"Schulte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Kathrin","family":"Ru\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunabh","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Dempfle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Laudes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"issue":"2","key":"3709_CR1","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1017\/S136898002000350X","volume":"24","author":"A Azzam","year":"2021","unstructured":"Azzam A. 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