Gut Microbiome Modulation by Dietary Polyphenols of Moringa oleifera: A Systems Pharmacology Approach in a Nigerian Metabolic Syndrome Cohort

Metabolic syndrome is an escalating public health crisis in Nigeria, driven by urbanisation and dietary transition across all geopolitical zones. Emerging evidence implicates gut microbiome dysbiosis in metabolic syndrome pathogenesis, and dietary polyphenols from Moringa oleifera present a culturally acceptable and widely available intervention candidate. This study employs a systems pharmacology approach integrating gut microbiome 16S rRNA amplicon sequencing, polyphenol-microbiome interaction modelling, and a randomised controlled trial to investigate the microbiome-modulatory effects of standardised Moringa oleifera leaf powder supplementation in a Nigerian metabolic syndrome cohort. One hundred adults with confirmed metabolic syndrome criteria recruited from primary health centres in Kano (North West), Enugu (South East), and Lagos (South West) were randomised to Moringa leaf powder (10 g/day) or placebo for 12 weeks. Faecal 16S rRNA sequencing (V3-V4 regions) was performed at baseline and week 12. Metabolic outcomes included waist circumference, fasting glucose, blood pressure, and lipid profile. In silico polyphenol-microbiome interaction modelling predicted Bifidobacterium and Lactobacillus enrichment by Moringa polyphenols. The intervention arm showed significant increase in microbiome alpha-diversity, enrichment of Bifidobacterium longum and Faecalibacterium prausnitzii, and reductions in Bacteroidetes-Firmicutes imbalance. Metabolic markers improved significantly in the Moringa group. This study provides the first systems pharmacology evidence for Moringa-mediated microbiome modulation in a Nigerian clinical context. Keywords: Moringa oleifera, gut microbiome, metabolic syndrome, polyphenols, systems pharmacology