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Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption
Cell Host & Microbe ( IF 30.3 ) Pub Date : 2017-08-24 , DOI: 10.1016/j.chom.2017.07.021
Kymberleigh A. Romano , Ana Martinez-del Campo , Kazuyuki Kasahara , Carina L. Chittim , Eugenio I. Vivas , Daniel Amador-Noguez , Emily P. Balskus , Federico E. Rey

Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.



中文翻译:

肠道细菌胆碱消耗的代谢,表观遗传和遗传转化效应

胆碱是表观遗传调控所需的必需营养素和甲基供体。在这里,我们通过设计缺乏单一胆碱利用酶的微生物群落,评估了肠道微生物胆碱代谢对细菌适应性和宿主生物学的影响。我们的结果表明,利用胆碱的细菌与宿主竞争这种营养,显着影响血浆和肝脏中甲基供体代谢产物的水平,并重现胆碱缺乏的生化特征。在高脂饮食的情况下,携带高水平消耗胆碱细菌的小鼠对代谢疾病的敏感性增加。此外,细菌诱导的甲基供体可用性的降低影响了成年小鼠及其后代的整体DNA甲基化模式,并引起了行为改变。我们的研究结果表明细菌胆碱代谢对宿主代谢,表观遗传学和行为的影响不足。这项工作表明,在确定最佳营养摄入量时应考虑人际间微生物代谢的差异。

更新日期:2017-08-24
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