The Effect of Oral Iron Supplementation on Gut Microbial Composition: a Secondary Analysis of a Double-Blind, Randomized Controlled Trial among Cambodian Women of Reproductive AgeOriginal paper
Karen 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.
Read MoreWhat was studied?
This study tested whether oral iron supplements shift the gut microbiome and favor iron-dependent enteropathogens. It compared two iron forms with differing bioavailability against placebo. It was a secondary analysis of a double-blind, randomized controlled trial. Stool was collected at baseline and after 12 weeks of daily supplementation. Gut communities were profiled by 16S rRNA gene sequencing, and targeted qPCR detected the enteropathogenic Escherichia coli virulence genes eae and bfpA.
Who was studied?
The analysis included 172 non-pregnant Cambodian women of reproductive age from rural Kampong Thom province. Arms were 59 receiving ferrous sulfate, 55 ferrous bisglycinate, and 58 placebo. Mean age was 34 years and mean body mass index 23.5. The population was largely iron-replete: only 4% were iron deficient and 1% had iron-deficiency anemia, though 17% were anemic overall. Ferrous sulfate delivered 60 mg elemental iron, ferrous bisglycinate 18 mg, and placebo contained microcrystalline cellulose. Sampling spanned early 2020.
What were the most important findings?
Iron supplementation did not significantly change gut alpha or beta diversity versus placebo. Communities were dominated by Bacteroidota (45.7%) and Firmicutes (42.1%). Ferrous bisglycinate produced a small but significant increase in the family Enterobacteriaceae versus placebo (p equals 0.026), which includes many Gram-negative enteric pathogens. qPCR found ferrous sulfate significantly raised odds of the EPEC virulence gene eae at endpoint (odds ratio 5.46, p equals 0.0104). The bfpA gene showed no trial-arm association.
What are the greatest implications of this study?
The results question blanket iron supplementation where iron deficiency is uncommon. Untargeted iron may enrich potential enteric pathogens without benefiting largely iron-replete women. The form of iron mattered. Ferrous sulfate was linked to a virulence gene of diarrheagenic E. coli, informing choices between iron salts and chelates in supplementation policy. Because pathogen signals were driven by a minority of samples, sampling was stool-based, and COVID-19 measures overlapped the trial, findings need confirmation in other reproductive-age populations.