An Integrated Metagenomic and Metabolomic Investigation of Microbiome-Metabolite Interactions in Childhood Stunting in North East Nigeria

Childhood stunting affects approximately one-third of children under five in North East Nigeria, with gut microbiome dysbiosis increasingly implicated as a mechanistic contributor to environmental enteropathy and growth faltering, yet integrated microbiome-metabolome studies in this population are entirely absent. This dissertation conducts an integrated metagenomic and metabolomic investigation of microbiome-metabolite interactions in stunted and non-stunted children in Borno and Yobe States, North East Nigeria. Stool and serum samples were collected from 90 stunted (height-for-age Z-score below -2) and 90 age- and sex-matched non-stunted children aged 12 to 36 months at primary healthcare centres in Maiduguri, Damaturu, and Nguru. Whole metagenome shotgun sequencing and untargeted metabolomics using LC-MS/MS were performed. Multi-omics integration used MMVEC and sparse CCA for microbiome-metabolite co-occurrence network construction. Stunted children had significantly lower gut microbiome diversity, with depletion of Bifidobacterium longum and Lactobacillus rhamnosus and enrichment of Prevotella copri and Fusobacterium nucleatum. Metabolomics identified reduced serum tryptophan and short-chain fatty acid levels alongside elevated branched-chain amino acid catabolites in stunted children. Co-occurrence network analysis revealed a Prevotella-driven metabolic shift reducing butyrate and indole-3-propionate synthesis, pathways linked to intestinal barrier function. The dissertation introduces an original Microbiome-Metabolite Stunting Pathway (MMSP) model providing mechanistic targets for microbiome-informed nutritional intervention. Keywords: childhood stunting, metagenomics, metabolomics, North East Nigeria, gut microbiome