Gut Microbiota and Iron: The Crucial Actors in Health and Disease Original paper

What was reviewed?

This review, Gut Microbiota and Iron in Health and Disease, synthesizes mechanistic and translational evidence showing how luminal iron availability reshapes gut microbial ecology and, in turn, how microbial activity influences intestinal iron handling and immune tone. The authors emphasize that oral iron therapy—although clinically effective for iron deficiency—often leaves substantial unabsorbed iron in the colon, where it becomes a powerful ecological “fertilizer” that can shift microbial competition, increase oxidative stress, and amplify inflammatory signaling at the host–microbe interface. The paper integrates core iron biology (duodenal uptake via DMT1 after ferric reduction; systemic regulation via hepcidin–ferroportin) with microbiome-specific processes such as siderophore-mediated iron scavenging, heme utilization strategies, and metabolite-driven changes in pH and iron speciation. It particularly highlights clinically relevant settings where iron–microbiome interactions matter most: iron supplementation in infants, inflammatory bowel disease (IBD) with iron-deficiency anemia, and colorectal cancer risk pathways mediated by inflammation and genotoxic microbial metabolites.

Who was reviewed?

Rather than evaluating a single cohort, the review draws on human observational studies, randomized fortification/supplementation trials, animal models (including germ-free vs specific-pathogen-free rodents and DSS colitis models), and in vitro colonic fermentation systems. The “populations” represented include infants receiving iron-fortified milk or micronutrient powders, school-aged children exposed to fortified foods, adults with iron deficiency or iron therapy exposure, and patients with IBD receiving oral versus intravenous iron. Experimental systems incorporate colonic microbial consortia grown under iron-replete versus iron-restricted conditions and rodent models where iron delivery route or dietary heme content is manipulated to probe dysbiosis, SCFA shifts, and inflammation.

Most important findings

Across study types, a consistent microbiome signature emerges: increased luminal iron tends to suppress beneficial anaerobes (notably Bifidobacterium and Lactobacillus in several infant/child studies) and enrich Proteobacteria—especially Enterobacteriaceae and E. coli—while altering SCFA metabolism and inflammatory markers. Classic infant data showed iron-fortified milk was associated with lower Bifidobacterium and higher Bacteroides and E. coli; later trials in African and Kenyan children similarly linked iron fortification to higher Enterobacteriaceae/pathogen abundance and inflammatory readouts such as calprotectin. Mechanistically, the review connects these shifts to microbial iron acquisition strategies (siderophores; heme uptake), redox changes in the gut lumen, and iron-driven reactive oxygen species that damage epithelium and promote inflammation, creating a feedback loop favoring inflammation-adapted pathobionts. Under iron-restricted conditions, some models show reductions in butyrate-producing taxa (e.g., Roseburia and Clostridium cluster IV members) and lower butyrate/propionate output, suggesting that both deficiency and excess can destabilize key metabolic functions depending on context. In IBD, oral iron is portrayed as a particular risk because it increases colonic luminal iron exposure; animal colitis models often show exacerbation, and a human comparison suggests oral—but not intravenous—iron can shift specific taxa such as Faecalibacterium prausnitzii and Bifidobacterium, alongside metabolomic changes. The review also highlights infection biology: iron availability can enhance virulence and replication of enteric pathogens such as Salmonella, Shigella, and Campylobacter, making iron a clinically relevant variable in diarrheal disease risk and colonization dynamics.

Key implications

Clinically, this review argues that oral iron is not microbiologically neutral: the unabsorbed fraction can restructure the colonic ecosystem toward pathobiont expansion, reduced barrier-supportive metabolism, oxidative epithelial stress, and heightened inflammatory tone, which is particularly relevant in infants (infection and inflammation risk) and in IBD (symptom worsening and dysbiosis amplification). For patients with active IBD and iron-deficiency anemia, the synthesis supports preferential consideration of intravenous iron when feasible, because it restores iron status while minimizing luminal iron exposure and microbiome disruption. More broadly, iron status should be treated as an ecological parameter when interpreting microbiome profiles in clinical studies and when building microbiome signature databases: taxa shifts in Proteobacteria/Enterobacteriaceae, Bifidobacterium, Lactobacillus, and butyrate-producing Firmicutes may reflect iron availability and delivery route as much as underlying disease biology.

Citation

Yilmaz B, Li H. Gut Microbiota and Iron: The Crucial Actors in Health and Disease. Pharmaceuticals (Basel). 2018;11(4):98. doi:10.3390/ph11040098