A spectrum of gut microbiota signatures predicts long-term health status.

MOTIVATION: The human gut microbiota is a complex ecosystem composed of hundreds of unique microbial species in a typical adult individual. Its composition has been linked to an individual's current and future health. At the population level, joint analysis of co-abundant species can capture associations with health status and other variables that cannot be robustly detected by analyzing individual taxa alone. Recently, the concept of enterosignatures was proposed to detect such co-abundant groups, decomposing microbial community variation into a mixture of five broad components of co-varying microbial taxa. However, their overall robustness, generalizability, and prospective potential in predicting long-term health status remain to be evaluated. RESULTS: We demonstrate that robust signatures of co-abundant species can be prospectively associated with mortality, diabetes, liver disease, and sepsis risk among Finnish adults in the FINRISK population cohort based on a 20-year follow-up. We characterized dysbiosis-associated signatures across varying levels of sub-ecosystem granularity, encompassing a previously reported Escherichia-driven signature as well as novel Prevotella subspecies-driven signatures linked to compromised future health status. These results illustrate the benefits of analyzing latent signatures across multiple levels of ecosystem granularity.