Xiao Ling, Van't Land Belinda, van de Worp Wouter R P H, Stahl Bernd, Folkerts Gert, Garssen Johan
Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.
Nutricia Research, Utrecht, Netherlands.
Front Immunol. 2017 Sep 28;8:1219. doi: 10.3389/fimmu.2017.01219. eCollection 2017.
Type 1 diabetes (T1D) is an immune-mediated disease with a strong genetic basis but might be influenced by non-genetic factors such as microbiome development that "programs" the immune system during early life as well. Factors influencing pathogenesis, including a leaky intestinal mucosal barrier, an aberrant gut microbiota composition, and altered immune responsiveness, offer potential targets for prevention and/or treatment of T1D through nutritional or pharmacologic means. In this review, nutritional approaches during early life in order to protect against T1D development have been discussed. The critical role of tolerogenic dendritic cells in central and peripheral tolerance has been emphasized. In addition, since the gut microbiota affects the development of T1D through short-chain fatty acid (SCFA)-dependent mechanisms, we hypothesize that nutritional intervention boosting SCFA production may be used as a novel prevention strategy. Current retrospective evidence has suggested that exclusive and prolonged breastfeeding might play a protective role against the development of T1D. The beneficial properties of human milk are possibly attributed to its bioactive components such as unique immune-modulatory components human milk oligosaccharides and metabolites derived thereof, including SCFAs. These components might play a key role in healthy immune development and creating a fit and resilient immune system in early and later life.
1型糖尿病（T1D）是一种具有强大遗传基础的免疫介导性疾病，但可能受非遗传因素影响，如微生物群发育，其在生命早期也会对免疫系统进行“编程”。影响发病机制的因素，包括肠道黏膜屏障渗漏、肠道微生物群组成异常和免疫反应性改变，为通过营养或药物手段预防和/或治疗T1D提供了潜在靶点。在本综述中，讨论了生命早期预防T1D发生的营养方法。强调了耐受性树突状细胞在中枢和外周耐受中的关键作用。此外，由于肠道微生物群通过短链脂肪酸（SCFA）依赖性机制影响T1D的发展，我们假设促进SCFA产生的营养干预可能用作一种新的预防策略。目前的回顾性证据表明，纯母乳喂养和延长母乳喂养时间可能对T1D的发生起到保护作用。母乳的有益特性可能归因于其生物活性成分，如独特的免疫调节成分人乳寡糖及其衍生的代谢产物，包括SCFA。这些成分可能在健康的免疫发育以及在生命早期和后期建立健康且有弹性的免疫系统中发挥关键作用。
