肠道菌群失调在2型糖尿病中的发病机制及治疗的研究进展

Research Progress on the Pathogenesis and Treatment of Intestinal Microbiota Dysbiosis in Type 2 Diabetes Mellitus

摘要: 2型糖尿病(Type 2 Diabetes Mellitus, T2DM)作为一种全球高发的慢性代谢性疾病，其核心病理特征表现为“进行性胰岛素抵抗(Insulin Resistance, IR)”与“胰岛β细胞功能代偿性衰退”共同作用导致的持续性高血糖状态。近年研究发现，T2DM患者普遍存在显著的“肠道菌群结构失调(Dysbiosis)”，其特征表现为微生物多样性降低、产短链脂肪酸菌丰度下降，而条件致病比例异常升高。这种菌群紊乱不仅是疾病的伴随现象，更通过“肠–胰轴”与“肠–脑轴”等多通路交互作用，直接参与T2DM及其并发症的发生发展与胰岛素抵抗的形成。本文对肠道菌群及其代谢产物参与T2DM相关代谢、炎症反应和免疫紊乱之间的复杂作用关系进行综述，分析肠道微生物及其代谢产物影响T2DM信号传导的机制。另外，简要探讨了通过调节肠道菌群及其代谢产物干预T2DM的治疗策略，同时阐述了肠道菌群对于2型糖尿病并发症的作用机制，为基于肠道菌群调控治疗T2DM提供理论依据与参考，使其针对菌群的干预策略呈现多元化发展；进一步揭示尽管干预菌群治疗T2DM前景广阔，但仍面临因果困境、个体异质性等的挑战，综上所述，肠道菌群作为T2DM诊疗的新靶标，其机制解析与干预策略研究正处于从群体干预向个体化治疗转化的关键阶段。深入理解肠道微生物组在T2DM网络中的生物学作用，将为T2DM及其并发症的防治开辟革命性路径。

Abstract: Type 2 Diabetes Mellitus (T2DM), a globally prevalent chronic metabolic disease, is characterized by persistent hyperglycemia resulting from the combined effects of “progressive Insulin Resistance (IR)” and “compensatory decline in pancreatic β-cell function” as its core pathological features. Recent studies have revealed that T2DM patients commonly exhibit significant “gut microbiota dysbiosis,” which is marked by reduced microbial diversity, decreased abundance of short-chain fatty acid-producing bacteria, and an abnormal increase in the proportion of opportunistic pathogens. This microbiota imbalance is not merely an accompanying phenomenon of the disease but also directly contributes to the development and progression of T2DM and its complications, as well as the formation of insulin resistance, through interactions across multiple pathways such as the “gut-pancreas axis” and “gut-brain axis.” This article reviews the complex roles of gut microbiota and their metabolites in T2DM-related metabolism, inflammatory responses, and immune dysregulation, analyzing the mechanisms by which gut microbes and their metabolites influence T2DM signaling pathways. Additionally, it briefly explores therapeutic strategies for intervening in T2DM through the modulation of gut microbiota and their metabolites, while elaborating on the mechanisms by which gut microbiota contribute to T2DM complications. This provides a theoretical basis and reference for T2DM treatment based on gut microbiota regulation, facilitating the diversified development of microbiota-targeted intervention strategies. It further highlights that despite the promising prospects of microbiota-based interventions for T2DM, challenges such as causal ambiguity and individual heterogeneity persist. In conclusion, gut microbiota represent a novel target for T2DM diagnosis and treatment, and research into their mechanistic dissection and intervention strategies is currently in a critical phase of transitioning from population-level interventions to individualized therapies. A deeper understanding of the biological role of the gut microbiome in the T2DM network will open up revolutionary avenues for the prevention and treatment of T2DM and its complications.