Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs of P. R. China, 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China.
Division of Toxicology, Wageningen University and Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Toxins (Basel). 2022 Mar 7;14(3):199. doi: 10.3390/toxins14030199.
In order to evaluate the potential differences between 3-Ac-DON and 15-Ac-DON in the human intestinal microbial metabolism, human fecal samples were anaerobically cultured in vitro. Quantitative fecal microbiota characteristics were obtained by 16S rRNA sequencing, and the data revealed several genera that may be relevant for the transformation of the acetylated DONs. Significant differences in the level of 3-Ac-DON and 15-Ac-DON conversion were observed among microbiota from different human individuals. 3-Ac-DON could be rapidly hydrolyzed; a ten-fold difference was observed between the highest and lowest in vitro conversion after 4 h. However, 15-Ac-DON was not fully transformed in the 4 h culture of all the individual samples. In all cases, the conversion rate of 3-Ac-DON was higher than that of 15-Ac-DON, and the conversion rate of 3-Ac-DON into DON varied from 1.3- to 8.4-fold that of 15-Ac-DON. Based on in vitro conversion rates, it was estimated that 45-452 min is required to convert all 3-Ac-DON to DON, implying that deacetylation of 3-Ac-DON is likely to occur completely in all human individuals during intestinal transit. However, for conversion of 15-Ac-DON, DON formation was undetectable at 4 h incubation in 8 out of the 25 human samples, while for 7 of these 8 samples conversion to DON was detected at 24 h incubation. The conversion rates obtained for these seven samples indicated that it would take 1925-4805 min to convert all 15-Ac-DON to DON, while the other 17 samples required 173-734 min. From these results it followed that for eight of the 25 individuals, conversion of 15-Ac-DON to DON was estimated to be incomplete during the 1848 min intestinal transit time. The results thus indicate substantial interindividual as well as compound specific differences in the deconjugation of acetylated DONs. A spearman correlation analysis showed a statistically significant relationship between deconjugation of both acetyl-DONs at 4 h and 24 h incubation. Based on the in vitro kinetic parameters and their scaling to the in vivo situation, it was concluded that for a substantial number of human individuals the deconjugation of 15-Ac-DON may not be complete upon intestinal transit.
为了评估 3-Ac-DON 和 15-Ac-DON 在人类肠道微生物代谢中的潜在差异，我们对人体粪便样本进行了体外厌氧培养。通过 16S rRNA 测序获得了定量粪便微生物群落特征，数据显示了几个可能与乙酰化 DON 转化相关的属。不同个体的微生物群落中，3-Ac-DON 和 15-Ac-DON 的转化水平存在显著差异。3-Ac-DON 可以迅速水解；在 4 小时后，体外转化的最高值与最低值相差 10 倍。然而，在所有个体样本的 4 小时培养中，15-Ac-DON 并未完全转化。在所有情况下，3-Ac-DON 的转化率均高于 15-Ac-DON，3-Ac-DON 转化为 DON 的转化率是 15-Ac-DON 的 1.3-8.4 倍。基于体外转化率，估计需要 45-452 分钟才能将所有 3-Ac-DON 转化为 DON，这意味着在肠道转运过程中，3-Ac-DON 的脱乙酰化可能会在所有个体中完全发生。然而，对于 15-Ac-DON 的转化，在 25 个人体样本中的 8 个样本中，在 4 小时孵育时未检测到 DON 的形成，而对于这 8 个样本中的 7 个样本，在 24 小时孵育时检测到转化为 DON。这 7 个样本的转化率表明，需要 1925-4805 分钟才能将所有 15-Ac-DON 转化为 DON，而其余 17 个样本需要 173-734 分钟。从这些结果可以推断，在 25 个个体中的 8 个个体中，估计在 1848 分钟的肠道转运时间内，15-Ac-DON 转化为 DON 不完全。结果表明，在脱乙酰化乙酰化 DON 方面存在显著的个体间和化合物特异性差异。Spearman 相关性分析表明，在 4 小时和 24 小时孵育时，两种乙酰-DON 的脱乙酰化之间存在统计学上显著的关系。基于体外动力学参数及其对体内情况的缩放，得出结论，对于大量人类个体而言，在肠道转运过程中，15-Ac-DON 的脱乙酰化可能不完全。
