Gut microbiota in type 2 diabetes mellitus: mechanistic links between dysbiosis, insulin resistance, and chronic low-grade inflammation
Year: 2026
Type: review
Abstract: It is becoming more well acknowledged that type 2 diabetes mellitus (T2DM) is a metabolic and inflammatory condition linked to microbiota that involves interrelated disruptions in intestinal integrity, immune control, and insulin signalling. Butyrate-producing bacteria, such as Faecalibacterium prausnitzii and Roseburia spp., are reduced in gut dysbiosis in type 2 diabetes, whereas opportunistic Gram-negative pathobionts that cause endotoxemia and mucosal inflammation proliferate. Increased intestinal permeability makes it easier for lipopolysaccharide (LPS) to translocate and activate the TLR4/MyD88/IKKβ/NF-κB pathway. This increases the production of TNF-α, IL-6, MCP-1, and IL-1β, which disrupt insulin signalling by serine phosphorylation of IRS-1 and subsequent inhibition of PI3K/Akt/GLUT4 function. Concurrently, JNK and NLRP3 inflammasome pathway activation increases oxidative stress, caspase-1 activation, and inflammatory β-cell damage. Simultaneously, decreased microbial-derived short-chain fatty acid synthesis impairs GPR41/GPR43- and HDAC-mediated signalling, which in turn affects AMPK activation, mitochondrial function, and enteroendocrine release of GLP-1 and PYY. FXR-FGF19 and TGR5-cAMP signalling are further disrupted by altered bile acid biotransformation, which encourages hepatic gluconeogenesis, fat buildup, and insulin resistance. Moreover, dysregulated branched-chain amino acid metabolism and overactivation of the mTOR/S6K1 pathway lead to chronic low-grade inflammation and metabolic rigidity. When taken as a whole, these interrelated microbiota-host signalling pathways are significant mechanistic contributors to the pathophysiology of type 2 diabetes and new treatment targets.
Source: Frontiers in Endocrinology
Authors: Yi Chen, Danru Jin, Xue Han, Xiaoting Liu, Yisi Liu, Li Wang
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7163149038