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Hydrogen metabolism shapes gut microbiome into health-associated configurations

Sola, M.; Hiol, A.; Viatli, G.; Fromentin, S.; Gilles, M.; Le Chatelier, E.; Morabito, C.; Plaza Onate, F.; Pons, N.; Quinquis, B.; Thirion, F.; Denis, J.; Leonard, R.; Cruaud, C.; Wincker, P.; Oliveira, P. H.; Le French Gut Consortium, ; Robbe Masselot, C.; Almeida, M.; Blottiere, H.; Dore, J.; Ehrlich, D. S.; Benamouzig, R.; Frioux, C.; Berland, M.; Veiga, P.

2026-05-07 microbiology
10.64898/2026.05.05.722951 bioRxiv
Show abstract

The human gut microbiome exhibits reproducible configurations, yet the ecological forces connecting them to health remain unclear. Here, using enterosignature-based stratification of 5,170 individuals from the Le French Gut cohort, we identified hydrogen disposal as a key determinant of population-scale microbiome configurations, independently replicated in a meta-cohort (n = 5,107). Microbial configurations followed a continuum of hydrogen recycling capacity and redox-associated functions, aligned with dietary patterns and health indicators. Methanogenesis-dominant partitions were associated with more favorable health profiles, whereas acetogenesis-enriched partitions exhibited features of low-grade inflammation, and increased digestive symptoms, perceived stress and antidepressant use. Experimental characterization of mucin profiles highlighted differences across partitions and alterations in Bacteroides-enriched configurations. Together, our findings support an ecological host-microbiome framework linking hydrogen metabolism, redox ecology, and host health, offering microbiome-informed targets for precision intervention. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/722951v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@e7b8d1org.highwire.dtl.DTLVardef@116ab09org.highwire.dtl.DTLVardef@136f1f8org.highwire.dtl.DTLVardef@480097_HPS_FORMAT_FIGEXP M_FIG C_FIG

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