4.5 Article

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

Journal

CELL CHEMICAL BIOLOGY
Volume 30, Issue 1, Pages 110-+

Publisher

CELL PRESS
DOI: 10.1016/j.chembiol.2022.12.001

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This article focuses on the responses of the gut microbiota to iron supplementation in humans. The study finds that iron can cause gradual changes in the composition of the microbiota, and deprivation of iron leads to growth inhibition and reduction in diversity. Individual species' sensitivity to iron deprivation can predict their dependency in a community. Exogenous heme serves as a source of inorganic iron to prevent depletion of certain species. The results highlight the importance of combining in vivo and in vitro studies in understanding the impact of environmental factors on the gut microbiota.
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.

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