Multi-Omics Investigation of the Gut Microbiome-Immune Axis in Malnutrition-Associated Immune Dysfunction Among Children in Rural North East Nigeria

The bidirectional relationship between gut microbiome composition and immune system development constitutes a critical mechanistic axis in childhood malnutrition, yet the specific molecular mediators linking gut dysbiosis to immune dysfunction remain incompletely characterized in Nigerian populations. This study applied a multi-omics approach integrating gut metagenomics, serum metabolomics, and immune phenotyping to investigate the gut microbiome-immune axis in 120 children aged 12 to 59 months (60 severely acutely malnourished and 60 age- and sex-matched well-nourished controls) in rural Adamawa and Borno States, North East Nigeria. Stool samples underwent 16S rRNA amplicon sequencing and shotgun metagenomics. Serum metabolomics was performed by untargeted LCMS. Immune phenotyping assessed circulating cytokines (IL-6, IL-10, TNF-alpha, IFN-gamma) and lymphocyte subset distributions by ELISA and flow cytometry. Integrative multi-omics analysis was performed using MaAsLin2 and Diablo frameworks. Results demonstrated significant gut dysbiosis in malnourished children characterized by Bifidobacterium depletion, Enterobacteriaceae enrichment, and reduced short-chain fatty acid-producing taxa. Serum butyrate and propionate levels were 60 to 80 percent lower in malnourished children, correlating inversely with pro-inflammatory cytokines. Immune phenotyping revealed CD4+ T-cell lymphopenia and elevated IL-6 in malnourished children. Multi-omics integration identified the butyrate-producing Roseburia intestinalis as a keystone mediator of the gut-immune axis in this context. This study makes an original multi-omics contribution to understanding malnutrition-associated immune failure in the North East zone and identifies microbiome-targeted dietary intervention targets. Keywords: gut microbiome, malnutrition, immune dysfunction, multi-omics, North East Nigeria.