Gut microbiota disorder-associated sphingomyelin: a key role in non-alcoholic fatty liver disease under aflatoxin B1 exposure

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in both humans and animals. Low dose of aflatoxin B1 (AFB1), a potent hepatotoxin, aggravated NAFLD. However, whether gut microbiome and its metabolites are involved in the aggravating effects of AFB1 on NAFLD remains unclear. The study aims to investigate the role of gut microbiome and metabolites in the aggravating effects of AFB1 on NAFLD. The results showed that AFB1 at 20, 40 and 80 μg/kg.bw for 4 weeks aggravated NAFLD as demonstrated by increasing lipid accumulation, inflammation and fibrosis. AFB1 at 40 μg/kg.bw aggravated gut microbiota disorders and intestinal barrier damage, elevated serum and liver sphingomyelin (SM) and ceramide (Cer) levels and necroptosis in CDAHFD-fed mice. Fecal microbiota from AFB1-treated mice aggravated NAFLD and necroptosis, and increased SM and Cer levels in CDAHFD-fed mice. SM treatment aggravated NAFLD and necroptosis just like that of AFB1. Myriocin, inhibitor of SM synthesis, alleviated the AFB1-aggravated NAFLD and necroptosis. Collectively, these results indicate that low dose of AFB1 induced gut microbiota dysbiosis, thereby aggravated SM accumulation, which in turn, aggravated NAFLD and necroptosis. Future studies will focus on identifying the key gut microbe responsible for SM accumulation.