Changes in Microbiota and Short-Chain Fatty Acids, Lipopolysaccharide-Binding Protein and Zonulin in People with Breast Cancer

Abstract Gut microbiota and its metabolites are increasingly recognized for their roles in cancer pathogenesis. This study aimed to identify differences in gut microbial composition and metabolic markers between breast cancer patients and healthy individuals. We compared newly diagnosed breast cancer patients with healthy controls. Fecal short-chain fatty acids (SCFAs) were measured using gas chromatography, while serum zonulin and lipopolysaccharide-binding protein (LBP) were quantified via ELISA. Gut microbiome composition was analyzed through 16S rRNA sequencing of 30 representative fecal samples. Analysis of 65 patients and 50 controls revealed significant microbial discrepancies at the family, genus, and species levels. Serum LBP levels were significantly higher in the breast cancer group in univariate analysis ( p = 0.007). In multivariable models adjusted for glucose and cholesterol, butyrate (molar %) remained a robust independent predictor of breast cancer (OR: 1.127, p = 0.042). However, LBP lost its significance in the multivariable model ( p = 0.169), suggesting its elevation is closely associated with the host’s metabolic profile rather than acting as a standalone driver. No significant differences were found in zonulin levels. Our findings demonstrate distinct microbial signatures and metabolic shifts in breast cancer. The independence of butyrate as a predictor, contrasted with the metabolism-dependent rise of LBP, highlights a complex gut-metabolic axis in breast cancer pathogenesis. Further large-scale research is needed to refine these markers for clinical use.