Gut Prevotella stercorea associates with protection against infection in rural African children

Understanding how the gut microbiome confers immune protection in early life remains a fundamental challenge, particularly in high-infection-burden, underrepresented populations. Here, we analyse longitudinal stool microbiome and illness data from 633 Gambian children aged 7–37 months enroled in a randomised, double-blind iron supplementation trial (NCT02941081). The primary endpoint was correction of iron deficiency anaemia, and the secondary endpoint was diarrhoea incidence and other adverse events; IHAT was non-inferior to ferrous sulphate for iron correction and showed fewer moderate-to-severe diarrhoea episodes. Using 16S rRNA sequencing at three timepoints (Days 1, 15, and 85), we find that children who remained infection-free harboured a consistently higher relative abundance of Prevotella stercorea, a keystone taxon of non-industrialised gut ecologies. In contrast, Escherichia coli and other opportunistic pathogens were enriched in children who developed infections. These taxonomic signatures were temporally stable and embedded within distinct, co-occurring microbial networks. Strikingly, higher P. stercorea abundance was inversely associated with both infection frequency and duration, with the greatest differences observed in children aged 1–2 years, potentially explaining their increased infectious risk. Our findings reveal a Prevotella-dominated enterotype associated with reduced infection risk, with implications for vaccine responsiveness, child survival, and microbiota-targeted interventions in global child health. © The Author(s) 2025.