Gut Microbiome Composition Is Predictive of Incident Type 2 Diabetes in a Population Cohort of 5,572 Finnish Adults

Abstract

<p>OBJECTIVE</p><p>To examine the previously unknown long-term association between gut microbiome composition and incident type 2 diabetes in a representative population cohort.</p><p>RESEARCH DESIGN AND METHODS</p><p>We collected fecal samples from 5,572 Finns (mean age 48.7 years; 54.1% women) in 2002 who were followed up for incident type 2 diabetes until 31 December 2017. The samples were sequenced using shotgun metagenomics. We examined associations between gut microbiome composition and incident diabetes using multivariable-adjusted Cox regression models. We first used the eastern Finland subpopulation to obtain initial findings and validated these in the western Finland subpopulation.</p><p>RESULTS</p><p>Altogether, 432 cases of incident diabetes occurred over the median follow-up of 15.8 years. We detected four species and two clusters consistently associated with incident diabetes in the validation models. These four species were <em>Clostridium citroniae</em> (hazard ratio [HR] 1.21; 95% CI 1.04–1.42), <em>C</em>. <em>bolteae</em> (HR 1.20; 95% CI 1.04–1.39), <em>Tyzzerella nexilis</em> (HR 1.17; 95% CI 1.01–1.36), and <em>Ruminococcus gnavus</em> (HR 1.17; 95% CI 1.01–1.36). The positively associated clusters, cluster 1 (HR 1.18; 95% CI 1.02–1.38) and cluster 5 (HR 1.18; 95% CI 1.02–1.36), mostly consisted of these same species.</p><p>CONCLUSIONS</p><p>We observed robust species-level taxonomic features predictive of incident type 2 diabetes over long-term follow-up. These findings build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome. The gut microbiome can potentially be used to improve disease prediction and uncover novel therapeutic targets for diabetes.</p>