Guangdong Provincial Key Laboratory of Food Quality and Safety/National-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, 483 Wushan Road, Tianhe District, Guangzhou, 510642, China.
Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China.
Food Funct. 2024 Apr 2;15(7):3615-3628. doi: 10.1039/d3fo04717b.
Aflatoxin B (AFB) causes serious immunotoxicity and has attracted considerable attention owing to its high sensitivity and common chemical-viral interactions in living organisms. However, the sensitivity of different species to AFB widely varies, which cannot be explained by the different metabolism in species. The gut microbiota plays a crucial role in the immune system, but the interaction of the microbiota with AFB-induced immunotoxicity still needs to be determined. Our results indicated that AFB exposure disrupted the structure of the gut microbiota and damaged the gut barrier, which caused translocation of microbiota metabolites, lipopolysaccharides, to the spleen. Subsequently, pyroptosis of the spleen was activated. Interestingly, AFB exposure had little effect on the splenic pyroptosis of pseudo-germfree mice (antibiotic mixtures eliminated their gut microbiota, ABX). Then, fecal microbiota transplant (FMT) and sterile fecal filtrate (SFF) were employed to validate the function of the gut microbiota and its metabolites in AFB-induced splenic pyroptosis. The AFB-disrupted microbiota and its metabolites significantly promoted splenic pyroptosis, which was worse than that in control mice. Overall, AFB-induced splenic pyroptosis is associated with the gut microbiota and its metabolites, which was further demonstrated by FMT and SFF. The mechanism of AFB-induced splenic pyroptosis was explored for the first time, which paves a new way for preventing and treating the immunotoxicity from mycotoxins by regulating the gut microbiota.
黄曲霉毒素 B（AFB）具有很高的敏感性，且在生物体内常与化学-病毒相互作用，因此会导致严重的免疫毒性，引起了人们的广泛关注。然而，不同物种对 AFB 的敏感性差异很大，这不能仅用物种间不同的代谢作用来解释。肠道微生物群在免疫系统中起着至关重要的作用，但微生物群与 AFB 诱导的免疫毒性之间的相互作用仍有待确定。我们的研究结果表明，AFB 暴露破坏了肠道微生物群的结构，破坏了肠道屏障，导致微生物群代谢物脂多糖向脾脏易位。随后，脾脏发生了细胞焦亡。有趣的是，AFB 暴露对伪无菌小鼠（抗生素混合物消除了其肠道微生物群，ABX）的脾脏细胞焦亡几乎没有影响。然后，采用粪便微生物群移植（FMT）和无菌粪便滤液（SFF）来验证肠道微生物群及其代谢物在 AFB 诱导的脾脏细胞焦亡中的作用。AFB 破坏的微生物群及其代谢物显著促进了脾脏细胞焦亡，比对照组小鼠更严重。总的来说，AFB 诱导的脾脏细胞焦亡与肠道微生物群及其代谢物有关，这通过 FMT 和 SFF 进一步得到了证实。首次探索了 AFB 诱导的脾脏细胞焦亡的机制，为通过调节肠道微生物群来预防和治疗霉菌毒素的免疫毒性开辟了新途径。
