Summary
In infants and young children, iron-fortified foods and iron-containing micronutrient powders lower protective bifidobacteria while increasing enterobacteria and pathogenic Escherichia coli, promoting gut inflammation and a modest rise in diarrhea risk. Most ingested fortificant iron is unabsorbed and reaches the colon, where it selectively benefits gram-negative enteropathogens over beneficial commensals.[1]
PubMed: https://pubmed.ncbi.nlm.nih.gov/29070552/
Key takeaways
- Iron fortification and iron-containing micronutrient powders lower protective bifidobacteria and lactobacilli while increasing enterobacteria and pathogenic E. coli in the infant gut.
- In randomized trials in Kenyan infants, both low (2.5 mg) and high (12.5 mg) daily iron doses raised the enterobacteria-to-bifidobacteria ratio and increased fecal calprotectin, a marker of gut inflammation.
- Added iron is associated with a modest increase in diarrhea risk, most pronounced in high-pathogen, low-sanitation settings.
- The mechanism is competition for luminal iron: most fortificant iron is unabsorbed and reaches the colon, where siderophore-producing enteropathogens out-compete low-iron-requiring commensals.
- The effect illustrates the metal-microbiome-disease axis, essentially nutritional immunity in reverse, though iron is an essential nutrient rather than a toxic heavy metal.
- Prebiotics (e.g., galacto-oligosaccharides), lower doses with absorption enhancers, and targeting truly iron-deficient children can mitigate the microbiome and diarrhea risks.
What the review examined
This review by Paganini and Zimmermann [1] synthesizes randomized controlled trials and mechanistic studies on how iron fortification and supplementation affect the developing gut microbiome, intestinal inflammation, and diarrhea in infants and young children. The focus is on low-income, high-infection settings in sub-Saharan Africa and South Asia, where iron-deficiency anemia is common and where iron is delivered as home-fortification micronutrient powders (MNPs), iron drops, or fortified complementary foods.
A central concern is that only a small fraction of orally administered iron is absorbed in the upper small intestine. In iron-replete or inflammation-affected infants, absorption is even lower, so the bulk of the dose (often 80 percent or more) passes into the colon, where the resident microbiota and enteropathogens compete for it. The review frames the infant gut as a uniquely vulnerable ecosystem because it is normally dominated by bifidobacteria, has an immature mucosal barrier, and is frequently exposed to enteric pathogens.
Key findings: a shift toward enterobacteria
Across trials, added iron consistently reduced the relative abundance of protective barrier commensals such as Bifidobacterium and Lactobacillus while increasing Enterobacteriaceae, including potentially pathogenic Escherichia coli, and clostridia. The enterobacteria-to-bifidobacteria ratio, a marker of an unfavorable, pathogen-leaning community, rose with iron.
The landmark supporting trial is Jaeggi and colleagues [2], two double-blind randomized controlled trials in 115 six-month-old Kenyan infants who consumed home-fortified maize porridge daily for four months. Both a low dose (2.5 mg iron as NaFeEDTA) and a high dose (12.5 mg iron as ferrous fumarate) increased enterobacteria, Escherichia/Shigella, the enterobacteria/bifidobacteria ratio, and Clostridium, and raised fecal calprotectin, a marker of intestinal inflammation. A smaller trial (33 Kenyan infants, 12.5 mg iron for three months)[3] found that the normal age-related decline in Escherichia/Shigella was blunted by iron and that Bifidobacterium fell in the iron group, corroborating the direction of effect.
Inflammation and diarrhea outcomes
The microbiome shift is accompanied by measurable gut inflammation. In the Kenyan trials, iron increased fecal calprotectin, consistent with an enterobacteria-enriched, pro-inflammatory mucosal environment. Because many enteric gram-negative pathogens depend on host iron acquisition for virulence and colonization, an iron-replete colonic lumen can favor their expansion and epithelial engagement.
The review concludes that iron-containing MNPs and supplements can produce a modest but real increase in diarrhea risk in young children, an effect most pronounced in settings with high pathogen exposure and inadequate sanitation. The magnitude is dose- and context-dependent, and the authors emphasize that the benefit of correcting iron deficiency must be weighed against these microbiome-mediated risks rather than assumed to be uniformly safe.
The mechanism: colonic iron feeds the wrong bacteria
The mechanistic thread is competition for luminal iron. Beneficial bifidobacteria and lactobacilli have low iron requirements and can persist under the iron-restricted conditions of the breastfed infant gut. Many Enterobacteriaceae, including pathogenic E. coli, Salmonella, and Shigella, are far more iron-avid and deploy high-affinity siderophores (such as enterobactin) and other iron-uptake systems to scavenge iron and out-compete commensals.
When unabsorbed fortificant iron floods the colon, it relaxes this natural iron restriction. The added iron disproportionately benefits siderophore-producing enteropathogens, raising their abundance and virulence potential, while offering little advantage to the low-iron-requiring commensals that normally provide colonization resistance. The net result is a community shift away from a bifidobacteria-dominated barrier state toward an enterobacteria-enriched, inflammation-prone state.
How it fits the metal-microbiome-disease axis
This literature provides human experimental evidence that changing intestinal iron availability can alter microbial composition and inflammation. Iron is nutritionally essential, and fortification can be beneficial. Microbial changes are a plausible contributor to adverse outcomes in some settings, but measuring both a microbial shift and diarrhea does not by itself establish that one mediated the other. Dose, formulation, iron status, and pathogen exposure matter.
The infant iron story is effectively the host's nutritional-immunity strategy run in reverse. Where the body normally sequesters iron to starve pathogens, excess luminal iron supplies it, tilting the ecological balance toward pathogens. It underscores a general principle of the axis: the microbiome sits between metal exposure and disease, and metal-driven changes in commensal-versus-pathogen balance are a plausible mechanistic route from exposure to clinical outcome. For essential metals this argues for careful dosing rather than avoidance.
Toward safer iron delivery
The review does not argue against treating iron deficiency, which carries serious consequences for infant growth and neurodevelopment. Instead it calls for formulations and strategies that minimize the amount of unabsorbed iron reaching the colon: lower iron doses paired with absorption enhancers, and co-delivery of prebiotics such as galacto-oligosaccharides (GOS).
Subsequent work tested a specific formulation: a 2024 randomized trial assigned 191 Kenyan infants to iron-fortified cereal with 7.5 g, 3 g, or no added GOS/FOS prebiotics for three weeks. Prebiotics increased iron absorption, assessed in a stable-isotope subset. The 7.5 g group had lower Enterobacteriaceae, pathogen abundance, and fecal calprotectin than the control group; both prebiotic groups had more Lactobacillus. These results support further study of this formulation and population, not a guarantee that any prebiotic prevents iron-related adverse effects. [4]
Correction — September 30, 2026. Distinguished measured microbial and clinical outcomes from causal mediation, and added a specific source, formulation, and duration for the prebiotic trial.
References
- Paganini D, Zimmermann MB (2017). The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review. American Journal of Clinical Nutrition 106(Suppl 6):1688S-1693S. View source↩1↩2
- Jaeggi T, Kortman GAM, Moretti D, et al. (2015). Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut, 64(5):731–742. View source↩
- Tang M, Frank DN, Hendricks AE, Ir D, Esamai F, Liechty E, Hambidge KM, Krebs NF. (2017). Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants. Nutrients, 9(7):776. View source↩
- Mikulic N, Uyoga MA, Stoffel NU, et al. (2024). Prebiotics increase iron absorption and reduce the adverse effects of iron on the gut microbiome and inflammation: a randomized controlled trial using iron stable isotopes in Kenyan infants. American Journal of Clinical Nutrition, 119(2):456–469. View source↩
Cite this page
Karen Pendergrass. (2025-11-14). Iron Fortification, the Infant Gut Microbiome, and Diarrhea Risk. Microbial Metallomics. https://microbialmetallomics.com/library/iron-fortification-infant-microbiome-diarrhea
This citation identifies this website page. The original source is available at the publisher or repository.
Published at https://microbialmetallomics.com/library/iron-fortification-infant-microbiome-diarrhea
Frequently asked questions
Does iron fortification harm the infant gut microbiome?
Controlled trials show that iron-fortified foods and iron-containing micronutrient powders can shift the infant gut microbiome unfavorably, decreasing beneficial bifidobacteria and lactobacilli while increasing enterobacteria and pathogenic Escherichia coli, and raising markers of gut inflammation such as fecal calprotectin.
Why does iron increase pathogenic E. coli and other enterobacteria?
Most orally administered iron is not absorbed and passes into the colon. Beneficial commensals like bifidobacteria need little iron, whereas enteropathogens such as E. coli, Salmonella, and Shigella are iron-avid and use high-affinity siderophores to scavenge it. Excess luminal iron therefore favors these pathogens over protective commensals.
Does iron supplementation cause diarrhea in infants?
Reviews of randomized trials conclude that iron-containing micronutrient powders and supplements can produce a modest increase in diarrhea risk in infants and young children, especially in settings with high pathogen exposure and poor sanitation. The effect is dose- and context-dependent, not universal.
How can iron be given more safely to infants?
Strategies include using lower iron doses with absorption enhancers, adding prebiotics such as galacto-oligosaccharides that improve absorption and help preserve beneficial bacteria, targeting iron to genuinely iron-deficient children, and supporting breastfeeding and sanitation to reduce pathogen exposure.