Table_2_Impact of intestinal microbiota on metabolic toxicity and potential detoxification of amygdalin.XLSX

Amygdalin (Amy) is metabolized into cyanide in vivo, which may lead to fatal poisoning after oral administration. The defense mechanisms against toxic cyanide have not yet been adequately studied. In this study, comparative toxicokinetics study of Amy was performed in normal and pseudo germ-free rats. The efficiency of cyanide release was significant higher in normal group when given a single oral dose of 440 mg/kg (50% median lethal dose). Thiocyanate, the detoxification metabolite, was firstly detected in feces, caecum, and intestinal microbiota incubation enzymic system. The results suggest intestinal microbiota is involved in bidirectional regulation of toxicity and detoxification of Amy. We further identified the species related to cyanogenesis of Amy with metagenomic sequencing, such as Bifidobacterium pseudolongum, Marvinbryantia formatexigens, and Bacteroides fragilis. Functional analysis of microbiota reveals the detoxification potential of intestinal microbiota for cyanide. Sulfurtransferase superfamily, such as rhodanese, considered as main detoxification enzymes for cyanide, are largely found in Coriobacteriaceae bacterium, Butyricicoccus porcorum, Akkermansia muciniphila, etc. Besides, cyanoamino acid metabolism pathway dominated by Escherichia coli may contribute to the detoxification metabolism of cyanide. In summary, intestinal microbiota may be the first line of defense against the toxicity induced by Amy.

苦杏仁苷（Amygdalin，简称Amy）在体内可代谢为氰化物，口服摄入后可能引发致命性中毒。目前针对毒性氰化物的防御机制尚未得到充分研究。本研究通过正常大鼠与伪无菌大鼠，开展苦杏仁苷的比较毒代动力学研究。当单次口服剂量为440mg/kg（半数致死量的50%）时，正常组的氰化物释放效率显著更高。解毒代谢产物硫氰酸盐首次在粪便、盲肠以及肠道菌群孵育酶体系中被检出。研究结果表明，肠道菌群参与了苦杏仁苷毒性与解毒过程的双向调控。本研究进一步通过宏基因组测序，鉴定出与苦杏仁苷产氰相关的菌种，包括假长双歧杆菌（Bifidobacterium pseudolongum）、解甲酸马文菌（Marvinbryantia formatexigens）以及脆弱拟杆菌（Bacteroides fragilis）。肠道菌群的功能分析揭示了其针对氰化物的解毒潜力：硫转移酶超家族（如硫氰酸酶）作为氰化物的主要解毒酶，广泛存在于科尔氏杆菌科（Coriobacteriaceae）细菌、猪丁酸球菌（Butyricicoccus porcorum）、嗜黏蛋白阿克曼氏菌（Akkermansia muciniphila）等菌株中。此外，由大肠杆菌（Escherichia coli）主导的氰基氨基酸代谢通路可能参与氰化物的解毒代谢过程。综上，肠道菌群或许是抵御苦杏仁苷引发毒性的第一道防线。