Bacteroides thetaiotaomicron, a Model Gastrointestinal Tract Species, Prefers Heme as an Iron Source, Yields Protoporphyrin IX as a Product, and Acts as a Heme Reservoir.

Members of the phylum are abundant in healthy gastrointestinal (GI) tract flora. Bacteroides thetaiotaomicron is a commensal heme auxotroph and representative of this group. are sensitive to host dietary iron restriction but proliferate in heme-rich environments that are also associated with colon cancer. We hypothesized that B. thetaiotaomicron may act as a host reservoir for iron and/or heme. In this study, we defined growth-promoting quantities of iron for B. thetaiotaomicron. B. thetaiotaomicron preferentially consumed and hyperaccumulated iron in the form of heme when presented both heme and nonheme iron sources in excess of its growth needs, leading to an estimated 3.6 to 8.4 mg iron in a model GI tract microbiome consisting solely of B. thetaiotaomicron. Protoporphyrin IX was identified as an organic coproduct of heme metabolism, consistent with anaerobic removal of iron from the heme leaving the intact tetrapyrrole as the observed product. Notably, no predicted or discernible pathway for protoporphyrin IX generation exists in B. thetaiotaomicron. Heme metabolism in congeners of B. thetaiotaomicron has previously been associated with the 6-gene operon, based on genetic studies. A bioinformatics survey demonstrated that the intact operon is widespread in but confined to members of the phylum and ubiquitous in healthy human GI tract flora. Anaerobic heme metabolism by commensal via is likely a major contributor to human host metabolism of the heme from dietary red meat and a driver for the selective growth of these species in the GI tract consortium. Research on bacterial iron metabolism has historically focused on the host-pathogen relationship, where the host suppresses pathogen growth by cutting off access to iron. Less is known about how host iron is shared with bacterial species that live commensally in the anaerobic human GI tract, typified by members of phylum . While many facultative pathogens avidly produce and consume heme iron, most GI tract anaerobes are heme auxotrophs whose metabolic preferences we aimed to describe. Understanding iron metabolism by model microbiome species like Bacteroides thetaiotaomicron is essential for modeling the ecology of the GI tract, which serves the long-term biomedical goals of manipulating the microbiome to facilitate host metabolism of iron and remediate dysbiosis and associated pathologies (e.g., inflammation and cancer).