{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:52:25Z","timestamp":1787025145247,"version":"build-2736575974"},"reference-count":38,"publisher":"American Diabetes Association","issue":"12","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"State of Bavaria"},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Biomedical Research Centre"},{"name":"SYSCID","award":["733100"],"award-info":[{"award-number":["733100"]}]},{"DOI":"10.13039\/501100004941","name":"Guy's and St Thomas' NHS Foundation Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004941","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018835","name":"Clinical Research Facility","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018835","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014013","name":"UKRI","doi-asserted-by":"crossref","award":["MR\/W026813\/1"],"award-info":[{"award-number":["MR\/W026813\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"crossref"}]},{"name":"AIM","award":["MR\/M016560\/1"],"award-info":[{"award-number":["MR\/M016560\/1"]}]},{"DOI":"10.13039\/501100013295","name":"Helmholtz Zentrum M\u00fcnchen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013295","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Zoe Limited"},{"DOI":"10.13039\/100011721","name":"Chronic Disease Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["212904\/Z\/18\/Z"],"award-info":[{"award-number":["212904\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"DiabetesUK","award":["19\/0006053"],"award-info":[{"award-number":["19\/0006053"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings. We linearly combined eight IFG-positively associated metabolites (1-methylxantine, nicotinate, glucuronate, uridine, cholesterol, serine, caffeine, and protoporphyrin IX) into an IFG-metabolite score, which was significantly associated with higher odds ratios (ORs) for IFG (TwinsUK: OR 3.9 [95% CI 3.02\u20135.02], P &amp;lt; 0.0001, KORA: OR 1.3 [95% CI 1.16\u20131.52], P &amp;lt; 0.0001) and incident type 2 diabetes (T2D; TwinsUK: hazard ratio 4 [95% CI 1.97\u20138], P = 0.0002). Although these are host-produced metabolites, we found that the gut microbiome is strongly associated with their fecal levels (area under the curve &amp;gt;70%). Abundances of Faecalibacillus intestinalis, Dorea formicigenerans, Ruminococcus torques, and Dorea sp. AF24-7LB were positively associated with IFG, and such associations were partially mediated by 1-methylxanthine and nicotinate (variance accounted for mean 14.4% [SD 5.1], P &amp;lt; 0.05). Our results suggest that the gut microbiome is linked to prediabetes not only via the production of microbial metabolites but also by affecting intestinal absorption\/excretion of host-produced metabolites and xenobiotics, which are correlated with the risk of IFG. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes and T2D onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We investigated whether there is a fecal metabolite signature of impaired fasting glucose (IFG) and the possible underlying mechanisms of action. We identified a fecal metabolite signature of IFG associated with prevalent IFG in two independent cohorts and incident type 2 diabetes in a subanalysis. Although the signature consists of metabolites of nonmicrobial origin, it is strongly correlated with gut microbiome composition. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes by affecting intestinal absorption or excretion of host compounds and xenobiotics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db23-0170","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T18:41:05Z","timestamp":1694544065000},"page":"1870-1880","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":12,"title":["A Fecal Metabolite Signature of Impaired Fasting Glucose: Results From Two Independent Population-Based Cohorts"],"prefix":"10.2337","volume":"72","author":[{"given":"Ana","family":"Nogal","sequence":"first","affiliation":[{"name":"1Department of Twin Research, King\u2019s College London, St Thomas\u2019 Hospital Campus, London, 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Augsburg, University of Augsburg, Augsburg, Germany"},{"name":"6ZIEL-Institute for Food & Health, Technische Universit\u00e4t M\u00fcnchen, Freising, Germany"},{"name":"7Institute for Medical Information Processing, Biometry, and Epidemiology, Medical Faculty, Ludwig-Maximilian University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Grallert","sequence":"additional","affiliation":[{"name":"3Institute of Epidemiology, Helmholtz Zentrum M\u00fcnchen, Research Unit of Molecular Epidemiology, German Research Center for Environmental Health (GmbH), Neuherberg, Germany"},{"name":"8German Center for Diabetes Research (DZD), Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Wawro","sequence":"additional","affiliation":[{"name":"5Epidemiology, University Hospital Augsburg, University of Augsburg, Augsburg, Germany"},{"name":"9Institute of Epidemiology, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Asnicar","sequence":"additional","affiliation":[{"name":"10Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Wong","sequence":"additional","affiliation":[{"name":"11Metabolon, Morrisville, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei-Florin","family":"Baleanu","sequence":"additional","affiliation":[{"name":"1Department of Twin Research, King\u2019s College London, St Thomas\u2019 Hospital Campus, London, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Michelotti","sequence":"additional","affiliation":[{"name":"11Metabolon, Morrisville, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Franks","sequence":"additional","affiliation":[{"name":"13Lund University Diabetes Center, Lund University, Malm\u00f6, Sweden"},{"name":"14Department of Clinical Sciences, Lund University, Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Bagnardi","sequence":"additional","affiliation":[{"name":"15Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim D.","family":"Spector","sequence":"additional","affiliation":[{"name":"1Department of Twin Research, King\u2019s College London, St Thomas\u2019 Hospital Campus, London, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordana T.","family":"Bell","sequence":"additional","affiliation":[{"name":"1Department of Twin Research, King\u2019s College London, St Thomas\u2019 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