Changes in the gut microbiome and neurotransmitters induced by mancozeb

Mancozeb is widely used as a broad-spectrum fungicide, and its potential effects on the gut-liver-kidney axis remain incompletely understood. In this study, we used an experimental oral exposure model to identify dose-associated effects and underlying mechanisms associated with mancozeb exposure. Following exposure to mancozeb at doses of 1, 10, and 100 mg/kg body weight, the fungicide was found to accumulate primarily in the digestive system (including the colon, cecum, and their contents) and feces of mice. Mancozeb exposure may exert adverse effects on the biomarkers related to liver function in mice, as evidenced by elevated activities of alanine aminotransferase and aspartate aminotransferase, increased malondialdehyde levels, and reduced activities of superoxide dismutase and glutathione peroxidase. Additionally, it caused significant shortening of the small intestine and increased intestinal permeability, reflected by elevated wet weight and dry-to-wet ratio of fecal particles, along with increased serum levels of creatinine, blood urea nitrogen, uric acid, and lipopolysaccharide. Mancozeb also markedly altered the gut microbiota structure, leading to an increased relative abundance of Lachnospiraceae_NK4A136_group (1.01-1.71-fold) and Ileibacterium (2.21-5.54-fold). Furthermore, mancozeb promoted the accumulation of acetylcholine, histamine release, and elevated levels of indole compounds in intestinal tissues. Transcriptomic analysis revealed upregulation of immune-related genes and downregulation of genes involved in drug metabolism. These results suggest that mancozeb exposure may affect gut microbiota composition, neurotransmitter and metabolite profiles, and the expression of functional genes related to immunity and detoxification. This study provides critical insights for the dietary health risk assessment of mancozeb.