Mancozeb exposure induces microbiome succession and neurotoxicity in the gut of mice

After of exposure to 1, 10, and 100 mg/kg bw mancozeb, it was mainly distributed in the digestive system (colon, cecum and their contents) and feces of mice. Mancozeb induced increased activities of alanine aminotransferase and aspartate aminotransferase as well as malondialdehyde content in mice, while decreasing activities of superoxide dismutase and glutathione peroxidase. Meanwhile, the length of small intestine in mice was significantly shortened, and the wet weight and dry to wet ratio of fecal particles, as well as the levels of creatinine, blood urea nitrogen, uric acid, and lipopolysaccharide in serum were increased, indicating that mancozeb induced liver and kidney damage and increased intestinal permeability in mice. Mancozeb exposure significantly altered the structural composition of the gut microbiota in mice, leading to an increased relative abundance of Lachnospiraceae_NK4A136_group (1.01-1.71-fold) and Ileibacterium (2.21-5.54-fold) compared to the control. Mancozeb led to the accumulation of acetylcholine, the release of histamine, and the increase of indole compound content in the intestinal tissues of mice. Moreover, the upregulation of immune related genes and the downregulation of drug metabolism related genes were also found. It is concluded that mancozeb altered gut microbiota structure, neurotransmitter and metabolite content, and expression pattern of immune and detoxification related functional genes in mice. The results provide a scientific basis for dietary health risk assessment of the fungicide mancozeb.