Gut microbiome stratification reveals functional metabolic signatures linked to host health

In the Le French Gut cohort (5,169 metagenomes), five-enterosignature partitioning links hydrogen disposal pathway gradients to host health, and these functional patterns replicate in an international meta-cohort (n = 5,107).

• Why it matters: Although gut microbiome taxonomic configurations are reproducible, the ecological and functional processes connecting them to health are unclear, limiting interpretable comparisons across studies.
• What they did: The authors applied the five-enterosignature (ES) model and built a rule-based framework to convert continuous microbiome variation into interpretable partitions, then compared functional and health-linked signatures across partitions.
• The result: Partitions enriched for Prevotella showed higher sulfate-reduction potential, ES-Firmicutes-associated partitions showed higher methanogenesis potential, and ES-Bacteroides-enriched partitions showed higher acetogenesis potential plus oxidative-stress and mucin-degradation signatures, altered fecal mucin O-glycosylation, and less favorable health indicators.

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