Iron Supplementation and Infant Gut Microbiota: Meta-Analysis Reveals Bifidobacterium Loss Original paper
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Read MoreKaren Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Metal Homeostasis
Metal Homeostasis
Transition metals like iron, zinc, copper, and manganese are crucial for the enzymatic machinery of organisms, but their imbalance can foster pathogenic environments within the gastrointestinal tract.
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Iron (Fe)
Iron (Fe)
OverviewIron is a pivotal nutrient at the host–pathogen interface. Virtually all microbes (with rare exceptions like Borrelia) require iron for processes from DNA synthesis to respiration. [1] In human hosts, free iron is vanishingly scarce due to “nutritional immunity,” wherein iron is locked up in hemoproteins or tightly bound by transport proteins.[2] This metal tug-of-war […]
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Karen Pendergrass
Read More
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was reviewed?
This systematic review and meta-analysis examined the effects of oral iron supplementation or fortification on the composition of gut microbiota in infants up to 12 months of age. The authors specifically evaluated changes in microbial taxa—particularly beneficial versus potentially pathogenic bacteria—in response to iron interventions. The review focused on randomized controlled trials (RCTs) comparing infants who received per os (oral) iron supplementation or iron-fortified foods versus controls who did not receive supplemental iron. The primary outcome was the alteration in gut microbiota, particularly shifts in the abundance of Bifidobacterium and Lactobacillus spp., as well as enteropathogens like Escherichia coli, Clostridium, and Shigella.
Who was reviewed?
Six RCTs met the inclusion criteria, involving healthy neonates and infants (≤12 months old) across various geographic locations—two studies in Africa, two in Europe, one in Canada, and one in the USA. Most infants were exclusively or predominantly breastfed at baseline, and interventions typically began around 6 months of age. Across studies, microbiome profiling methods varied but largely relied on 16S rRNA sequencing of the V1–V4 hypervariable regions, although one early study (1985) used bacterial culturing methods.
Most important findings
The meta-analysis focused on Bifidobacterium due to limited compatible data across studies for other taxa. Four studies provided sufficient quantitative data to evaluate changes in Bifidobacterium abundance:
| Comparison Group | Mean Reduction in Bifidobacterium | 95% CI | p-value |
|---|---|---|---|
| Iron Group | -10.3% | -15.0% to -5.55% | |
| Non-Iron Group | -2.96% | ||
| Total Difference | -6.37% | -10.16% to -25.8% | 0.02 |
The next table summarizes key microbial findings from the systematic review and meta-analysis on oral iron supplementation in infants. Across all included studies, Bifidobacterium was consistently reduced following iron exposure. Lactobacillus spp. remained relatively stable, though data were insufficient for quantitative synthesis. Several pathogenic taxa, including Escherichia/Shigella and Clostridium, increased in certain iron groups, but inter-study variability prevented pooled analysis. A quality appraisal using the RoB2 tool showed that most studies were at low risk of bias, while two presented methodological concerns related to blinding and analysis planning.
| Category | Summary |
|---|---|
| Bifidobacterium | Consistently reduced in iron-supplemented groups across all studies. |
| Lactobacillus spp. | Generally stable or modestly decreased; insufficient data for inclusion in meta-analysis. |
| Pathogenic Taxa | Escherichia/Shigella and Clostridium increased in iron supplemented groups. However, data was too heterogeneous to pool. |
Key implications
Iron supplementation or fortification in infancy, while clinically important for preventing iron deficiency anemia, may reduce beneficial taxa such as Bifidobacterium, which play crucial roles in infant gut maturation, immune development, and metabolic regulation. This reduction was statistically significant across pooled studies. Although not all studies observed an increase in pathogenic bacteria, prior research outside this meta-analysis (e.g., Jaeggi et al., 2015; Paganini et al., 2017) suggests that iron may support the bloom of enteropathogens and increase the risk of inflammation or diarrhea. Given that Bifidobacterium dominance in infancy is associated with protection against allergic disease, gastrointestinal infection, and potentially neurodevelopmental resilience, these findings reinforce the importance of optimizing iron formulation. Iron interventions should be cautiously balanced—favoring strategies like co-administration with prebiotics (e.g., galacto-oligosaccharides) to preserve microbiome health without compromising hematologic outcomes.
The review underscores a clinical paradox: iron is vital for neurodevelopment, yet excessive or poorly absorbed iron in the colon may create an unfavorable gut environment. Further studies are needed to determine the safest formulations and dosing schedules that mitigate microbiota disruption while effectively correcting iron deficiency.
Citation
Karamantziani T, Pouliakis A, Xanthos T, Ekmektzoglou K, Paliatsiou S, Sokou R, Iacovidou N. The Effect of Oral Iron Supplementation/Fortification on the Gut Microbiota in Infancy: A Systematic Review and Meta-Analysis.Children. 2024;11(2):231. doi:10.3390/children1102023