Gut Microbiome-Metabolome Interactions and Their Influence on Non-Communicable Disease Risk in Urban and Rural Nigerian Populations

The gut microbiome-metabolome axis is increasingly recognized as a modifiable determinant of non-communicable disease risk, and characterising its composition and functional output in Nigerian populations with distinct urban and rural exposures provides a unique contribution to global microbiome science and to understanding of Nigeria's non-communicable disease transition. This dissertation characterises gut microbiome composition, faecal and plasma metabolome profiles, and their interactions in urban and rural Nigerian populations, examining associations with non-communicable disease risk biomarkers. A balanced cross-sectional study recruited two hundred urban residents from Ibadan and two hundred rural residents from Kwara State farming communities, matched for age, sex, and ethnicity. Gut microbiome composition was profiled by deep 16S rRNA gene V3-V4 amplicon sequencing and shotgun metagenomics on a subset. Faecal metabolomics was performed by untargeted GC-MS and LC-MS/MS. Plasma metabolomics targeted short-chain fatty acids, bile acid profiles, trimethylamine N-oxide, branched-chain amino acids, and aromatic amino acids. Non-communicable disease risk biomarkers included insulin resistance (HOMA-IR), CRP, blood pressure, lipid profile, and obesity measures. Urban residents showed significantly reduced microbiome alpha diversity, reduced Prevotella to Bacteroides ratio, and significantly lower faecal butyrate compared to rural residents. Plasma trimethylamine N-oxide was significantly elevated in urban residents and correlated significantly with HOMA-IR and CRP. Mediation analysis confirmed that faecal butyrate significantly mediated the association between rural lifestyle and lower HOMA-IR. Random forest modelling identified microbiome-derived metabolites as stronger predictors of non-communicable disease risk phenotypes than dietary intake variables alone. Keywords: gut microbiome, metabolomics, non-communicable disease, urban-rural comparison, Nigeria.