The collection of fecal material and developments in sequencing technologies have enabled cost-efficient, standardized, and non-invasive gut microbiome profiling. As a result, microbiome composition data from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases.1-5 In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterized due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data.6-8 Here, we analyse the long-term association between gut microbiome variation and mortality in a large, well-phenotyped, and representative population cohort (n = 7211, FINRISK 2002; Finland).9 We report specific taxonomic and functional signatures related to the Enterobacteriaceae family in the human gut microbiome that predict mortality during a 15-year follow-up. These associations can be observed both in the Eastern and Western Finns who have differing genetic backgrounds, lifestyles, and mortality rates.10,11 Our results supplement previously reported cross-sectional associations,1-4,12 and help to establish a methodological and conceptual basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status. These findings could serve as a solid framework for microbiome profiling in clinical risk prediction, paving the way towards clinical applications of human microbiome sequencing aimed at prediction, prevention, and treatment of disease.

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