The impact of iron and heme availability on the healthy human gut microbiome in vivo and in vitro

Responses of the indigenous human gut commensal microbiota to iron are poorly understood because of an emphasis on in vitro studies of pathogen iron sensitivity. In a study of iron supplementation in healthy hu-mans, we identified gradual microbiota shifts in some participants correlated with bacterial iron internaliza-tion. To identify direct effects due to taxon-specific iron sensitivity, we used participant stool samples to derive diverse in vitro communities. Iron supplementation of these communities caused small compositional shifts, mimicking those in vivo, whereas iron deprivation dramatically inhibited growth with irreversible, cu-mulative reduction in diversity and replacement of dominant species. Sensitivity of individual species to iron deprivation in axenic culture generally predicted iron dependency in a community. Finally, exogenous heme acted as a source of inorganic iron to prevent depletion of some species. Our results highlight the comple-mentarity of in vivo and in vitro studies in understanding how environmental factors affect gut microbiotas.