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.

doi:10.64898/2026.05.05.722951

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bioRxiv · 10.64898/2026.05.05.722951

Hydrogen metabolism shapes gut microbiome into health-associated configurations

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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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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. Hydrogen metabolism shapes gut microbiome into health-associated configurations. https://doi.org/10.64898/2026.05.05.722951

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