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This study evaluates the preventive and metabolic\u2011regulatory potential of D\u2010threitol, a novel sugar alcohol synthesized by engineered\n                      <jats:italic>Yarrowia lipolytica<\/jats:italic>\n                      , in a high\u2010fat diet and streptozotocin\u2010induced T2DM mice model. In vitro, D\u2010threitol acted as a competitive inhibitor of \u03b1\u2010glucosidase. After eight weeks of oral administration (500\u00a0mg\/kg\/day), treated mice exhibited reduced weight gain and fat accumulation, improved glucose tolerance and insulin sensitivity, and better lipid profiles, along with attenuated tissue injury in the liver, kidney, and pancreas. Notably, D\u2010threitol intervention significantly reshaped the gut microbiota, enhancing microbial diversity, enriching beneficial genera (e.g.,\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      ,\n                      <jats:italic>Allobaculum<\/jats:italic>\n                      ), and restoring fecal short\u2010chain fatty acids (SCFAs) levels, particularly acetate, propionate, and butyrate. Molecular docking and dynamics simulations demonstrated stable binding of D\u2010threitol to \u03b1\u2010glucosidase, supported by favorable binding energy and hydrogen\u2011bond formation. D\u2010threitol shows promise as a safe dietary ingredient for the prevention and management of T2DM, mediated through dual mechanisms involving enzymatic inhibition and microbiota modulation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1750-3841.70968","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:53:46Z","timestamp":1772970826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Novel Sugar Alcohol D\u2010Threitol Alleviates Type 2 Diabetes Mellitus and Modulates Gut Microbiota in Mice"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6862-0331","authenticated-orcid":false,"given":"Qing","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology Shanghai Jiao Tong University  Shanghai 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