Quercetin Modulates Gut Microbiome and Immune Response to Mitigate Arsenic‐Induced Toxicity: Insights From a Microbiome‐Immune Study

Arsenic exposure from contaminated food and water is a global nutritional issue. Nutritional interventions indicate that dietary polyphenols, such as quercetin, may reduce these toxic effects via antioxidant and immunomodulatory properties. This study examined the protective effect of quercetin against arsenic-induced toxicity in a Wistar rat model. Twenty-four adult Wistar rats were divided into four groups as follows: control (G0), arsenic-exposed (G1; 5 mg/kg/day NaAsO₂), quercetin-treated (G2; approximately 50 mg/kg/day), and co-treated (G3; arsenic + quercetin). Over 28 days, catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD), cytokine gene expression (IL-1β, IL-6, TNF-α, IL-4, IL-10, TGF-β), claudin, occludin (CLDN1, OCLN), and fecal microbial profiles (q-PCR, diversity index) were assessed. Our results demonstrate that arsenic exposure significantly reduces antioxidant enzyme levels, elevates pro-inflammatory cytokines, disrupts tight junction protein expression, and causes dysbiosis and proliferation of Proteobacteria and E. coli, ultimately damaging intestinal structure. Quercetin treatment, especially in G3, restored antioxidant levels, balanced cytokine profiles, normalized tight junction gene expression, and maintained gut microbial diversity. Histopathological and correlation analyses also confirmed structural and functional recovery of gut tissues. These findings support quercetin's potential as a dietary intervention to counteract heavy metal-induced gut disorders, reinforcing its nutritional relevance in environmental toxins.