Gut Microbiome Composition and Its Modulation of Haematological Inflammatory Biomarkers in Nigerian Sickle Cell Disease Patients: An Original Metagenomic Investigation

This dissertation investigates the gut microbiome composition in Nigerian sickle cell disease patients and develops an original analytical framework for understanding how microbiome dysbiosis modulates haematological inflammatory and haemostatic biomarkers that drive SCD pathophysiology. The gut microbiome is an emerging modifier of inflammatory and haematopoietic processes, but its characterisation in SCD has been exclusively performed in American and European patient populations using diet patterns and microbial exposures fundamentally different from those in Nigeria. A cross-sectional design with a nested longitudinal substudy was conducted at Lagos University Teaching Hospital and University of Nigeria Teaching Hospital. Stool samples from 150 HbSS patients in steady state, 50 HbAS carriers, and 50 HbAA controls were subjected to shotgun metagenomics at 10 gigabases coverage per sample. Microbial community characterisation used KrakenUniq and MetaPhlAn4. Plasma inflammatory markers (TNF-alpha, IL-6, IL-18, CXCL5), haemostatic markers (vWF, D-dimer, sP-selectin), and haemolysis markers (LDH, bilirubin) were correlated with microbial taxa by multivariate MaAsLin2 analysis. HbSS patients showed significantly reduced alpha diversity and depletion of butyrate-producing taxa including Faecalibacterium prausnitzii and Roseburia inulinivorans. Butyrate-producer abundance correlated inversely with plasma IL-18 and sP-selectin, providing mechanistic evidence for microbiome-mediated inflammatory attenuation. The dissertation proposes the Nigerian SCD Microbiome Inflammatory Axis Framework as an original theoretical contribution, with probiotic intervention implications. Keywords: gut microbiome, sickle cell disease, metagenomics, inflammatory biomarkers, Nigeria.