The Role of Microbiome-Parasite Interactions in Modulating Malaria Susceptibility in Nigerian Children: A Longitudinal Cohort Study

Emerging evidence from high-income countries and a limited number of African studies suggests that the composition of the gut and skin microbiome modulates malaria vector attraction and Plasmodium parasite development, yet longitudinal data from high-transmission Nigerian settings are virtually absent. This doctoral research investigates microbiome-parasite interactions and their role in determining malaria susceptibility in Nigerian children using a prospective longitudinal cohort design. Three hundred and sixty children aged 1 to 5 years in Ondo State, South West Nigeria were enrolled and followed for 24 months across two malaria transmission seasons. Stool samples for gut microbiome profiling by 16S rRNA amplicon sequencing were collected at baseline, six, 12, and 24 months. Skin microbiome swabs were collected from the ankle and forearm at equivalent timepoints. Malaria episodes were confirmed by Giemsa microscopy and parasite density quantified. Time-to-first-infection and total malaria episode frequency were used as susceptibility outcomes. Mixed-effects models assessed the prospective association between microbiome diversity indices and malaria outcomes, controlling for bednet use, nutritional status, prior immunity markers, and antibiotic exposure. Evidence from 2020 to 2024 identifies specific Lactobacillaceae and Akkermansia species as negatively associated with malaria incidence in Malian children, suggesting a novel biological modulation pathway. This study extends this evidence base to a high-transmission southern Nigerian context and explores seasonal microbiome shifts as modifiers of malaria risk. Keywords: gut microbiome, malaria susceptibility, Nigerian children, longitudinal cohort, 16S rRNA sequencing.