Department of Biological Sciences
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Item CHARACTERIZATION OF THE GUT MICROBIOME AND INFLAMMATORY MARKERS IN TREATMENT-NAIVE TRIPLE-NEGATIVE BREAST CANCER (TNBC) PATIENTS IN LAGOS, NIGERIA(Covenant University Ota, 2025-10) OGUNLEYE, Oluwanifemi Omodara; Covenant University DissertationTriple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen, progesterone, and HER2 receptors. Emerging studies suggest that gut microbial imbalance and chronic inflammation may contribute to breast cancer progression. This study investigated the gut microbiome profile and circulating inflammatory markers in treatment-naive TNBC patients compared with unknown subtypes and healthy controls to understand the microbiome–inflammation relationship in TNBC pathogenesis. Fecal DNA from TNBC, unknown subtype, and healthy control groups was extracted and analyzed using 16S rRNA sequencing through the Nephele QIIME2 pipeline. Alpha diversity was evaluated with the Shannon index, and group differences were tested using the Kruskal–Wallis and Mann–Whitney tests. Serum IL-6 and TNF-α levels were quantified using ELISA, and correlations were assessed using Pearson and Spearman analyses. Alpha diversity analysis revealed no statistically significant difference among groups (Kruskal–Wallis p = 0.298), though TNBC samples exhibited lower and more variable Shannon index values compared with controls. TNBC samples showed unstable high levels of Firmicutes, and Bacteriodota, and varying low levels of Proteobacteria and Actinobacteriota, indicating microbial imbalance. IL-6 and TNF-α levels did not differ significantly between TNBC and controls (p > 0.05), though TNBC patients displayed higher variability. A moderate positive correlation was found between IL-6 and TNF-α in TNBC (r = 0.5982), indicating co-regulated inflammatory activity. The PICRUSt functional prediction revealed altered microbial metabolic pathways in TNBC patients compared to controls, particularly a reduction in butyrate and propionate metabolism associated with short-chain fatty acid production. The findings suggest early gut dysbiosis and immune imbalance in TNBC despite the absence of significant statistical differences. Reduced microbial diversity, altered phylum-level composition, and cytokine co-regulation indicate biological perturbations in treatment-naive TNBC. These findings collectively support a potential link between microbial dysbiosis, altered short-chain fatty acid metabolism and elevated inflammatory activity in TNBC pathogenesis. It also highlights the need for larger, longitudinal studies to validate microbial and inflammatory biomarkers for early disease characterization.