Deconstructing the role of iron and heme in the structure of healthy human gut microbial communities

Abstract

The response of the human gut microbiome to disruptions is often difficult to discern without model systems that remove the complexity of the host environment. Fluctuations in iron availability provide a case in point: the responses of pathogenic bacteria to iron in vitro are much better understood than those of the indigenous human gut commensal microbiota. In a clinical study of iron supplementation in healthy humans, we identified gradual, participant-specific microbiota shifts correlated with bacterial iron internalization. To identify direct effects due to taxon-specific iron sensitivity, we used stool samples from these participants as inocula to derive in vitro communities. Iron supplementation of these communities caused small shifts in structure, similar to in vivo, whereas iron deprivation dramatically inhibited growth with irreversible and cumulative reduction in diversity and replacement of some dominant species. Sensitivity of individual species to iron deprivation during growth in axenic culture generally predicted iron dependency in a community context. Finally, exogenous heme acted as a source of inorganic iron to prevent depletion of some community members. Our results highlight the complementarity of in vivo and in vitro studies in deconstructing how environmental factors affect gut microbiome structure.