肠道菌群影响糖尿病视网膜病变发生的人群流行病学研究

糖尿病视网膜病变（DR）传统防控策略的核心是血糖控制，但血糖控制稳定后DR仍发生，或长年控制不佳但DR一直未发生等现象很常见，其原因不明，对防控工作带来负面影响。目前公认高纤维膳食可减少DR发生，我们前期研究也发现上述DR一直未发生者日常膳食中纤维比例较高，同时其肠道益生菌丰度明显增加。鉴于膳食可改变肠道菌群，基础实验已证实肠道菌群特有的代谢产物SFCAs、SBA和LPS都可独立于血糖之外影响DR的发生，而我们也确认在DR人眼内SFCAs量发生明显改变，因此推测肠道菌群通过这些代谢产物影响了DR的发生，这有待人群研究证实。为此，本研究拟对长期随访的糖尿病队列中成年和青少年患者进行连续4年前瞻性队列研究，筛选出与DR发生相关的肠道菌群多样性标志物以及对应的代谢产物变化特征，明确其影响DR发生的机制。这将为实现以特定肠道菌群为靶点的早期干预技术，完善DR防控策略提供理论依据。

The well-accepted strategy for prevention and early-stage treatment of diabetic retinopathy (DR) is maintaining blood glucose in a proper low level. However, in population-based and clinical studies, it is always observed that DR still occurs in diabetic patients with low blood glucose level, or never occurs in some diabetic patients with high blood glucose level. Because the related factors are still unknown, it is quite difficult to find out high risk patients, and that obviously limits the effects of traditional DR prevention and early-stage treatment strategy. Nowadays, more and more studies have recognized that a high-fiber diet is inversely related to DR. Our previous studies got the same results, and found that the abundance of intestinal probiotics was significantly increased in those who did not experience DR under high blood glucose level. It is known that the diet changes the intestinal flora and then directly regulates host metabolism and immunity; the unique metabolites of the intestinal flora, SFCAs, SBA and LPS, can affect the occurrence of DR without affecting the blood glucose, and our previous metabolomic studies confirmed that in the eyes of DR, SFCAs decreased significantly, which is consistent with the changes of intestinal probiotics. Therefore, it is speculated that changes in intestinal flora have a protective effect on DR occurrence. No population-based studies have confirmed this speculation so far. In the present study, we intend to conduct a 4-year prospective cohort observation of adult and juvenile diabetic patients in two diabetes cohorts that have been followed for many years, to screen out the unique intestinal flora diversity related to DR occurrence and clarify the corresponding characteristics of SFCAs, SBA and LPS changes in blood, aiming to provide theoretical evidence of the mechanism of DR protection by specific intestinal flora diversity, and further improve the existing prevention and control strategies of DR with intestinal flora as the target. The present grant application is in line with the guideline of National Science Foundation of China (NSFC) which now supports cohort epidemiology study on eye diseases.