{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:39:11Z","timestamp":1791819551101,"version":"4.3.4"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>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\/IKK\u03b2\/NF-\u03baB pathway. This increases the production of TNF-\u03b1, IL-6, MCP-1, and IL-1\u03b2, 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 \u03b2-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.<\/jats:p>","DOI":"10.3389\/fendo.2026.1856667","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:28:45Z","timestamp":1780374525000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Gut microbiota in type 2 diabetes mellitus: mechanistic links between dysbiosis, insulin resistance, and chronic low-grade inflammation"],"prefix":"10.3389","volume":"17","author":[{"given":"Yi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Preventive Treatment of Disease, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine","place":["Liaoning, 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