Taxonomic Signatures of Long-Term Mortality Risk in Human Gut Microbiota

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. 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. 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). 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. Our results supplement previously reported cross-sectional associations, 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.