Oral iron-induced stunting is associated with increased Christensenella abundance in a piglet model for human infants

Purpose Iron deficiency anaemia (IDA) affects around 40% of < 5-year-olds globally. Unfortunately, IDA treatment by oral iron intervention often causes diarrhoea, thought to be linked to iron-induced changes in the gut microbiota. Piglets are valuable preclinical models for human infants since they share many physiological characteristics, have similar gut microbial populations and, if left untreated with iron, reliably develop IDA. We hypothesised that IDA and different forms of iron supplementation (oral and injection) would have differential effects on the gut microbiota that would consequently differentially impact immune and metabolic development during infancy. Methods 24 one-day-old piglets were litter-matched into 4 treatment groups (n = 6): control (no iron); intramuscular iron (IM, 200mg Fe); oral iron (200mg FeSO 4 /kg feed); IM+oral iron combined. Results As expected, the iron-free treatment piglets developed IDA. This was combined with stunted growth and corresponding changes in plasma metabolites and immune parameters. However, although all 3 iron treatments prevented the development of IDA, piglets receiving oral iron were also stunted (compared to those which received IM iron; 14–19% weight-gain reduction over 27 days, p <0.05). This stunting was linked to significant changes in the expression of immune-associated proteins in the gut and specific bacterial genera, but not plasma metabolites. Importantly, the correlation between oral-iron treatment, reduced weight gain and increased Christensenella abundance provides novel evidence linking iron-induced stunting with Christensenella . Conclusion The findings relayed here thus raise health concerns for infants receiving iron-fortified formula milk and/or those in LMICs enrolled in blanket oral iron supplementation programs.