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The termite fungus comb is an integral component of nests of termites, which are a global pest. Termite fungus comb polysaccharides (TFCPs) have been identified to possess antioxidant, anti-aging, and immune-enhancing properties. However, their physicochemical characteristics and their role in fighting diabetes have not been previously reported. In the current study, TFCPs were isolated and structurally characterized. The yield of TFCPs was determined to be 2.76%, and it was found to be composed of a diverse array of polysaccharides with varying molecular weights. The hypoglycemic and hypolipidemic effects of TFCPs, as well as their potential mechanisms of action, were investigated in a T2D mouse model. The results demonstrated that oral administration of TFCPs could alleviate fasting blood glucose levels, insulin resistance, hyperlipidemia, and the dysfunction of pancreatic islets in T2D mice. In terms of mechanisms, the TFCPs enhanced hepatic glycogenesis and glycolysis while inhibiting gluconeogenesis. Additionally, the TFCPs suppressed hepatic de novo lipogenesis and promoted fatty acid oxidation. Furthermore, the TFCPs altered the composition of the gut microbiota in the T2D mice, increasing the abundance of beneficial bacteria such as Allobaculum and Faecalibaculum, while reducing the levels of pathogens like Mailhella and Acetatifactor. Overall, these findings suggest that TFCPs may exert anti-diabetic effects by regulating hepatic glucose and lipid metabolism and the composition of the gut microbiota. These findings suggest that TFCPs can be used as a promising functional ingredient for the prevention and treatment of T2D.<\/jats:p>","DOI":"10.3390\/ijms25137430","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T12:21:03Z","timestamp":1720441263000},"page":"7430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Termite Fungus Comb Polysaccharides Alleviate Hyperglycemia and Hyperlipidemia in Type 2 Diabetic Mice by Regulating Hepatic Glucose\/Lipid Metabolism and the Gut Microbiota"],"prefix":"10.3390","volume":"25","author":[{"given":"Haihan","family":"Xiao","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5131-214X","authenticated-orcid":false,"given":"Xudong","family":"Song","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilin","family":"Li","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senhua","family":"Qin","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofu","family":"Huang","sequence":"additional","affiliation":[{"name":"Nanning Institute of Termite Control, Nanning 530023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beimin","family":"Wu","sequence":"additional","affiliation":[{"name":"Nanning Institute of Termite Control, Nanning 530023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Jia","sequence":"additional","affiliation":[{"name":"Nanning Institute of Termite Control, Nanning 530023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qionghua","family":"Gao","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Agri-Environmental and Agri-Products Safety, National Demonstration Center for Experimental Plant Science Education, College of Agriculture, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4306-4648","authenticated-orcid":false,"given":"Ziyi","family":"Song","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nrendo.2017.151","article-title":"Global Aetiology and Epidemiology of Type 2 Diabetes Mellitus and Its Complications","volume":"14","author":"Zheng","year":"2018","journal-title":"Nat. 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