Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, Switzerland.
Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.
Front Endocrinol (Lausanne). 2024 Sep 26;15:1425235. doi: 10.3389/fendo.2024.1425235. eCollection 2024.
The incidence of type-1 diabetes is on the rise, particularly in developed nations, and predominantly affects the youth. While genetic predisposition plays a substantial role, environmental factors, including alterations in the gut microbiota, are increasingly recognized as significant contributors to the disease.
In this study, we utilized germ-free non-obese diabetic mice to explore the effects of microbiota colonization during early life on type-1 diabetes susceptibility.
Our findings reveal that microbiota introduction at birth, rather than at weaning, significantly reduces the risk of type-1 diabetes, indicating a crucial window for microbiota-mediated modulation of immune responses. This protective effect was independent of alterations in intestinal barrier function but correlated with testosterone levels in male mice. Additionally, early life colonization modulated T cell subset frequencies, particularly T helper cells and regulatory T cells, in the intestine, potentially shaping type-1 diabetes predisposition.
Our findings underscore the pivotal role of early-life microbial interactions in immune regulation and the development of autoimmune diseases.
1 型糖尿病的发病率呈上升趋势，特别是在发达国家，主要影响年轻人。虽然遗传易感性起着重要作用，但环境因素，包括肠道微生物群的改变，越来越被认为是疾病的重要诱因。
在这项研究中，我们使用无菌非肥胖型糖尿病小鼠来探讨生命早期微生物定植对 1 型糖尿病易感性的影响。
我们的研究结果表明，出生时而不是断奶时引入微生物群可显著降低 1 型糖尿病的风险，这表明微生物群介导的免疫反应调节存在关键窗口期。这种保护作用与肠道屏障功能的改变无关，但与雄性小鼠的睾丸酮水平相关。此外，生命早期的定植还调节了肠道中 T 细胞亚群的频率，特别是辅助性 T 细胞和调节性 T 细胞，这可能影响了 1 型糖尿病的易感性。
我们的研究结果强调了生命早期微生物相互作用在免疫调节和自身免疫性疾病发展中的关键作用。
