Alterations in gut flora composition and function of the host have become a crucial area in the pathogenesis of type 2 diabetes. This paper aims to discuss the molecular biological mechanisms of type 2 diabetes, including glucose metabolism, inflammation, intestinal barrier function, and immunomodulation. It reviews studies on the signaling pathways related to the metabolites of the intestinal flora affecting the host. This will provide the basis for subsequent clinical targeted therapy and an outlook on future research.

Li Lianchun, Qie Yulong, Li Qin. Exploring the Molecular Biological Mechanisms of Type 2 Diabetes Mellitus Based on Intestinal Flora Metabolites that Affect Host-Associated Signaling Pathways. Frontiers in Medical Science Research (2024), Vol. 6, Issue 6: 73-79. https://doi.org/10.25236/FMSR.2024.060611.

[1] Zhu DL. Guideline for the prevention and treatment of type 2 diabetes mellitus in China(2020 edition)(Part 1)[J]. Chinese Journal of Practical Internal Medicine. 2021,41(8):668-695.

[2] Hasain Z, Mokhtar NM, Kamaruddin NA, et al. Gut microbiota and gestational diabetes mellitus: a review of host-gut microbiota interactions and their therapeutic potential[J]. Front Cell Infect Microbiol. 2020,3(15)10-18. 

[3] Nicholson JK, Holmes E, Kinross J, et al. Host-gut microbiota metabolic interactions[J]. Science. 2012 Jun 8;336(6086):1262-7. 

[4] Zhou Z, Sun B, Yu D, et al. Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus[J]. Front Cell Infect Microbiol. 2022 Feb 15;12:834485.

[5] Samadi N, Heiden D, Klems M, et al. Gastric enzyme supplementation inhibits food allergy in a BALB/c mouse model[J]. Nutrients. 2021,13(3)26-38.

[6] Noureldein M, Nawfal R, Bitar S, et al. Intestinal microbiota regulates diabetes and cancer progression by IL-1β and NOX4-dependent signaling cascades[J]. Cell Mol Life Sci. 2022,79(9)502. 

[7] Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice[J]. Diabetes. 2008 Jun;57(6):1470-81. 

[8] Creely S. J, McTernan P. G, Kusminski C. M, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. American Journal of Physiology[J]. Endocrinology and Metabolism. 2007;292(3):E740–E747.

[9] Han YR. Study on acupuncture and acupoint pressure combination to improve glycolipid metabolism disorder and microenvironment in T2DM intestinal barrier[D]. Changchun University of Traditional Chinese Medicine, 2022.

[10] Wahlström A, Sayin S, Marschall H, et al. Intestinal Crosstalk Between Bile Acids and Microbiota and Its Impact on Host Metabolism[J]. Cell Metab. 24 (1), 41–50. 

[11] Fujisaka S, Ussar S, Clish C, et al. Antibiotic effects on gut microbiota and metabolism are host-dependent [J]. J Clin Invest. 2016,126(12):4430-4443.

[12] Zhao T, Gu J, Zhang H, et al. Sodium Butyrate-Modulated Mitochondrial Function in High-Insulin Induced HepG2 Cell Dysfunction[J]. Oxid. Med. Cell. Longev. 2020, 1904609.

[13] Adamberg K, Kolk K, Jaagura M, et al. The composition and metabolism of fecal microbiota is specifically modulated by different dietary polysaccharides and mucin: an isothermal microcalorimetry study[J]. Benef Microbes. 2018,9(1)21-34. 

[14] Chen LC , Fan ZY , Wang HY, et al. Effect of polysaccharides from adlay seed on anti-diabetic and gut microbiota[J]. Food Funct. 2019,10(7)4372-4380. 

[15] Sun Y, Jin C, Zhang X, et al. Restoration of GLP-1 secretion by Berberine is associated with protection of colon enterocytes from mitochondrial overheating in diet-induced obese mice[J]. Nutr Diabetes. 2018 Sep 24;8(1):53.

[16] Koh A, Molinaro A, Ståhlman M, et al. Microbially produced imidazole propionate impairs insulin signaling through mTORC1[J]. Cell. 2018;175(4):947–961.e17. 

[17] Wang J, He Y, Yu D, et al. Perilla oil regulates intestinal microbiota and alleviates insulin resistance through the PI3K/AKT signaling pathway in type-2 diabetic KKAy mice[J]. Food Chem Toxicol. 2020,1(35)965-110. 

[18] Chu LL, Guo ZH, Hou JY, et al. Progress on pharmacological effects of cinnamaldehyde in prevention and treatment of diabetes[J]. Drugs & Clinic, 2023,38(2):483-487.

[19] Liu C. Effects of Epigallocatechin-3-gallate on Insulin Resistance and Intestinal Microbiota in Type 2 Diabetic Rats[D]. Qingdao University, 2020.

[20] Huang Yanqin. The Study on the intervention mechanism of jianpixiaokefang for the expression of nesfatin-1 and AMPK/mTORC1/SAD-A signaling pathway in diabetic mice pancreas[D]. Shandong University of Traditional Chinese Medicine, 2014.

[21] Vaez H, Najafi M, Rameshrad M, et al. AMPK activation by metformin inhibits local innate immune responses in the isolated rat heart by suppression of TLR 4-related pathway[J]. Int Immunopharmacol. 2016,4(34)501-507.

[22] Maynard CL, Elson CO, Hatton RD, et al. Reciprocal interactions of the intestinal microbiota and immune system[J]. Nature. 2012,489(741)231-241.

[23] Hu FH, Liang XL, Huang XY et al. Mechanism of Natural Plant Essential Oil in Intervention in Type 2 Diabetes Mellitus: A Review[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2023,3(2)1-7.

[24] Wang F, He HL, Hua J, et al. Based on the prediction of intestinal microbiota function, the effect of Gegenqinlian decoction on inflammatory factors in KKAy mice was observed[J]. Lishizhen Medicine and Materia Medica Research, 2022,33(10)2365-2368.

[25] Xu N, Zhou Y, Lu X, et al. Auricularia auricula-judae (Bull.) polysaccharides improve type 2 diabetes in HFD/STZ-induced mice by regulating the AKT/AMPK signaling pathways and the gut microbiota[J]. J Food Sci. 2021,86(12)5479-5494. 

[26] Suresh S, Irvine AE. The NOTCH signaling pathway in normal and malignant blood cell production[J]. J Cell Commun Signal. 2015,9(1)5-13.

[27] Peng X, Wang K, Wang Y, et al. Exploration of the mechanism of the control of coccidiosis in chickens based on network pharmacology and molecular docking with the addition of modified gegen qinlian decoction[J]. Front Vet Sci. 2022,17(9)518-584.