Thirion, F. | bioRxiv Science

bioRxiv2026

Hydrogen metabolism shapes gut microbiome into health-associated configurations

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

microbiology↗

bioRxiv2022

In vitro modelling of oral microbial invasion in the human colon

Recent advances in the human microbiome characterization have revealed significant oral microbial detection in stools of dysbiotic patients. However, little is known about the potential interactions of these invasive oral microorganisms with commensal intestinal microbiota and host. In this proof of concept study, we propose a new model of oral to gut invasion by the combined use of an in vitro model simulating both the physicochemical and microbial (lumen and mucus-associated microbes) parameters of the human colon (M-ARCOL), a salivary enrichment protocol and whole metagenome shotgun sequencing. Oral invasion of the intestinal microbiota was simulated by injection of enriched saliva in the in vitro colon model inoculated with faecal sample from the same healthy adult donor. The mucosal compartment of M-ARCOL was able to retain the highest species richness levels over time, whilst it decreased in the luminal compartment. This study also showed that oral microorganisms preferably colonized the mucosal microenvironment, suggesting potential oral-to-intestinal mucosal competitions. This new model of oral-to-gut invasion can provide useful mechanistic insights into the role of oral microbiome in various disease processes.

microbiology↗