Das Soumik, Devi Rajeswari V, Venkatraman Ganesh, Elumalai Ramprasad, Dhanasekaran Sivaraman, Ramanathan Gnanasambandan
School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.
Department of Nephrology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, Tamil Nadu 600116, India.
Transl Res. 2024 Mar;265:71-87. doi: 10.1016/j.trsl.2023.11.002. Epub 2023 Nov 10.
Diabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus (DM) that poses a serious risk as it can lead to end-stage renal disease (ESRD). DKD is linked to changes in the diversity, composition, and functionality of the microbiota present in the gastrointestinal tract. The interplay between the gut microbiota and the host organism is primarily facilitated by metabolites generated by microbial metabolic processes from both dietary substrates and endogenous host compounds. The production of numerous metabolites by the gut microbiota is a crucial factor in the pathogenesis of DKD. However, a comprehensive understanding of the precise mechanisms by which gut microbiota and its metabolites contribute to the onset and progression of DKD remains incomplete. This review will provide a summary of the current scenario of metabolites in DKD and the impact of these metabolites on DKD progression. We will discuss in detail the primary and gut-derived metabolites in DKD, and the mechanisms of the metabolites involved in DKD progression. Further, we will address the importance of metabolomics in helping identify potential DKD markers. Furthermore, the possible therapeutic interventions and research gaps will be highlighted.
糖尿病肾病(DKD)是糖尿病(DM)的一种主要微血管并发症,因其可导致终末期肾病(ESRD)而构成严重风险。DKD与胃肠道中微生物群的多样性、组成和功能变化有关。肠道微生物群与宿主生物体之间的相互作用主要由微生物代谢过程从膳食底物和内源性宿主化合物产生的代谢产物介导。肠道微生物群产生的大量代谢产物是DKD发病机制中的一个关键因素。然而,对肠道微生物群及其代谢产物促成DKD发生和发展的确切机制的全面理解仍不完整。本综述将总结DKD中代谢产物的现状以及这些代谢产物对DKD进展的影响。我们将详细讨论DKD中的主要代谢产物和肠道衍生代谢产物,以及参与DKD进展的代谢产物的机制。此外,我们将阐述代谢组学在帮助识别潜在DKD标志物方面的重要性。此外,还将强调可能的治疗干预措施和研究空白。