Lactiplantibacillus plantarum MTCC 25433 and Quercetin Blend Ameliorate Benzo[a]pyrene-Induced Gut Dysregulation in a Murine Model
摘要
Benzo[a]pyrene (B[a]P), a carcinogenic food contaminant, is implicated in colonic abnormalities, including colorectal cancer. This study evaluated the synergistic potential of a novel synbiotic blend of Lactiplantibacillus plantarum MTCC 25433 (9 log CFU/d) and quercetin (25 mg/kg/d) against B[a]P-induced gut dysregulation in Swiss albino mice. Oral B[a]P exposure (50 mg/kg, twice weekly for 28 days) disrupted the intestinal homeostasis, enhancing lipid peroxidation (+ 44.1%), proinflammatory cytokines levels (TNF-α: + 69.6%, IL-6: + 52.9%), inflammatory transcription factors (Nf-κB: 1.92-fold, Foxa2: 2.92-fold) and mucin expression (Muc-2: 2.9-fold), and perturbed gut barrier integrity (Occludin: 0.61-fold, Cldn-4: 0.14-fold). The synbiotic blend exhibited superior efficacy compared to MTCC 25433 or quercetin alone, mitigating MDA (− 32%), TNF-α (− 66%), IL-6 (− 59%), Nf-κB: − 38%, Foxa2: − 51%, Muc-2 (− 57%), Occludin (+ 129%) and Cld-4 (+ 352%) levels and further resulted in enhanced B[a]P fecal excretion (29.5 to 182 μg/g). Two-way ANOVA analysis confirmed synergistic interactions specifically for reductions in adipose tissue B[a]P levels, metabolic enzyme expression (Cyp1b1), gut barrier integrity (Cldn-4), and microbiome modulation, notably Firmicutes, Lachnospiraceae, Clostridium and Ruminococcus, along with enhanced butyrate concentrations. Histopathological analysis confirmed the protective effects of a synbiotic blend against B[a]P-mediated adipocyte disruption and necrosis in the hepatic and intestinal tissues. Principal component analysis also supported its synergistic efficacy in alleviating B[a]P toxicity. Overall, these findings demonstrated the potent anti-inflammatory, antioxidant and gut-modulating potential of the synbiotic blend, suggesting its potential as a promising dietary approach for mitigating the harmful effects of the food contaminant, B[a]P.
Graphical Abstract