The impact of iron and heme availability on the healthy human gut microbiome in vivo and in vitro. Issue 1 (19th January 2023)

• Record Type: Journal Article
• Authors: Celis, Arianna I.; Relman, David A.; Huang, Kerwyn Casey
• Is Part Of: Cell chemical biology. Volume 30:Issue 1(2023)
• Page Start: 110
• Page End: 126.e3
• Publication Date: 2023-01-19
• Subjects: microbiome perturbations -- heme -- in vitro models of the gut microbiome -- iron metabolism -- Lachnospiraceae -- Bacteroidaceae -- Burkholderiaceae -- Enterococcaceae -- Enterobacteriaceae; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2022.12.001
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: 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 humans, we identified gradual microbiota shifts in some participants correlated with bacterial iron internalization. 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, cumulative 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 complementarity of in vivo and in vitro studies in understanding how environmental factors affect gut microbiotas. Graphical abstract: Highlights: Iron supplementation elicits small, person-specific effects on healthy gut microbiomes Iron deprivation gradually leads to irreversible changes in community structure Taxon-specific sensitivity to iron deprivation can predict changes in a community Heme buffers effects of iron deprivation by acting as a source of inorganic iron Abstract : In vitro communities enable characterization of perturbation-specific effects on community structure outside the complex host environment. By pairing a human study of the effects of iron supplementation on the gut microbiome with in vitro community experiments, we provide a foundation for further characterization of iron metabolism in healthy human gut communities.