Institute of Pharmacology & Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, CNC.IBILI Consortium & CIBB Consortium, University of Coimbra, Coimbra, Portugal.
Institute of Pharmacology & Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, CNC.IBILI Consortium & CIBB Consortium, University of Coimbra, Coimbra, Portugal; Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy, Coimbra, Portugal.
Biochim Biophys Acta Mol Basis Dis. 2019 Jul 1;1865(7):1876-1897. doi: 10.1016/j.bbadis.2018.09.032. Epub 2018 Oct 1.
The increased prevalence of type 2 diabetes mellitus (T2DM) and life expectancy of diabetic patients fosters the worldwide prevalence of retinopathy and nephropathy, two major microvascular complications that have been difficult to treat with contemporary glucose-lowering medications. The gut microbiota (GM) has become a lively field research in the last years; there is a growing recognition that altered intestinal microbiota composition and function can directly impact the phenomenon of ageing and age-related disorders. In fact, human GM, envisaged as a potential source of novel therapeutics, strongly modulates host immunity and metabolism. It is now clear that gut dysbiosis and their products (e.g. p-cresyl sulfate, trimethylamine‑N‑oxide) dictate a secretory associated senescence phenotype and chronic low-grade inflammation, features shared in the physiological process of ageing ("inflammaging") as well as in T2DM ("metaflammation") and in its microvascular complications. This review provides an in-depth look on the crosstalk between GM, host immunity and metabolism. Further, it characterizes human GM signatures of elderly and T2DM patients. Finally, a comprehensive scrutiny of recent molecular findings (e.g. epigenetic changes) underlying causal relationships between GM dysbiosis and diabetic retinopathy/nephropathy complications is pinpointed, with the ultimate goal to unravel potential pathophysiological mechanisms that may be explored, in a near future, as personalized disease-modifying therapeutic approaches.
2 型糖尿病（T2DM）的患病率增加和糖尿病患者的预期寿命延长促进了全球范围内视网膜病变和肾病的发生，这两种主要的微血管并发症一直难以用现代降糖药物治疗。肠道微生物群（GM）在过去几年中已成为一个活跃的研究领域；人们越来越认识到，肠道微生物群落组成和功能的改变会直接影响衰老和与年龄相关的疾病现象。事实上，人类 GM 被视为一种潜在的新型治疗药物来源，它强烈调节宿主的免疫和代谢。现在很清楚，肠道菌群失调及其产物（例如 p- 邻甲苯磺酸盐、三甲胺 N-氧化物）决定了与分泌相关的衰老表型和慢性低度炎症，这是衰老的生理过程（“炎症衰老”）以及 T2DM（“代谢炎症”）及其微血管并发症所共有的特征。这篇综述深入探讨了 GM、宿主免疫和代谢之间的相互作用。此外，它还描述了老年和 T2DM 患者的人类 GM 特征。最后，全面审查了最近关于 GM 失调与糖尿病视网膜病变/肾病并发症之间因果关系的分子发现（例如表观遗传变化），最终目标是阐明可能在不久的将来作为个性化疾病修饰治疗方法进行探索的潜在病理生理机制。
