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.