Gut microbiota in type 2 diabetes mellitus: mechanistic links between dysbiosis, insulin resistance, and chronic low-grade inflammation
- 1Department of Preventive Treatment of Disease, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine
- 2Department of Cardiology I, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine
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.
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BibTeX
@article{chen2026microbiota,
title = {{Gut microbiota in type 2 diabetes mellitus: mechanistic links between dysbiosis, insulin resistance, and chronic low-grade inflammation}},
author = {Yuehua Chen and Danru Jin and Xue Han and Xiaoting Liu and Yisi Liu and Li Wang},
journal = {Frontiers in Endocrinology},
year = {2026},
month = jun,
doi = {10.3389/fendo.2026.1856667},
url = {https://doi.org/10.3389/fendo.2026.1856667},
note = {CC BY},
}
RIS
TY - JOUR
TI - Gut microbiota in type 2 diabetes mellitus: mechanistic links between dysbiosis, insulin resistance, and chronic low-grade inflammation
AU - Yuehua Chen
AU - Danru Jin
AU - Xue Han
AU - Xiaoting Liu
AU - Yisi Liu
AU - Li Wang
PY - 2026
DA - 2026/06/02
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1856667
UR - https://doi.org/10.3389/fendo.2026.1856667
AB - 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.
SN - 1664-2392
ER -