Liang Jiahui, Chu Yunhang, Chen Xingyu, Leng Yan
Gastroenterology, Changchun University of Traditional Chinese Medicine, Changchun, Jilin, China.
Department of Liver, Spleen and Gastroenterology, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin, China.
Front Endocrinol (Lausanne). 2025 Oct 31;16:1664233. doi: 10.3389/fendo.2025.1664233. eCollection 2025.
Metabolic-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) frequently co-exist on the pathological basis of dysregulated glucose and lipid metabolism, forming a bidirectional causal relationship. The upstream mechanisms underlying this association require further elucidation. Recent studies suggest that the interactive network comprising the "gut-adipose axis" and "gut-pancreatic axis" represents a core component of the comorbidity mechanism. This network initiates with gut microbiota dysbiosis, which alters short-chain fatty acids (SCFAs), lipopolysaccharide (LPS), branched-chain amino acids (BCAAs), secondary bile acids(SBAs), and other microbial metabolites, as well as endocrine signals such as the endocannabinoid system (ECS) and incretin hormones. This network simultaneously influences adipose tissue and the pancreas to coordinate glucose and lipid homeostasis. Therefore, this paper proposes the "Common Messengers, Dual-Axis Convergence" model to systematically elucidate how the gut microbiota, through a shared set of messenger molecules, simultaneously and independently drives lipid and glucose metabolic dysregulation via the gut-adipose and gut-pancreatic axes, ultimately leading to the comorbidity of MAFLD and T2DM.
代谢相关脂肪性肝病（MAFLD）和2型糖尿病（T2DM）常基于葡萄糖和脂质代谢失调的病理基础同时存在，形成双向因果关系。这种关联的上游机制尚需进一步阐明。近期研究表明，由“肠-脂肪轴”和“肠-胰腺轴”组成的交互网络是合并症机制的核心组成部分。该网络始于肠道微生物群失调，这会改变短链脂肪酸（SCFAs）、脂多糖（LPS）、支链氨基酸（BCAAs）、次级胆汁酸（SBAs）和其他微生物代谢产物，以及诸如内源性大麻素系统（ECS）和肠促胰岛素等内分泌信号。该网络同时影响脂肪组织和胰腺，以协调葡萄糖和脂质稳态。因此，本文提出“共同信使，双轴汇聚”模型，以系统地阐明肠道微生物群如何通过一组共享的信使分子，同时并独立地通过肠-脂肪轴和肠-胰腺轴驱动脂质和葡萄糖代谢失调，最终导致MAFLD和T2DM的合并症。
