{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:35:01Z","timestamp":1788622501093,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82260640"],"award-info":[{"award-number":["82260640"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Intestinal dysbiosis is a pivotal trigger of type 2 diabetes mellitus (T2DM). Our previous studies confirmed that composite probiotics derived from fermented camel milk (CPCM), containing Lactobacillus harbinensis and 13 other strains, can ameliorate glucose and lipid metabolism in T2DM mice by reshaping bile acid profiles, and its effect may be associated with the PPAR\u03b3-LXR\u03b1-NPC1L1 signaling pathway. Methods: Metagenomic analysis characterized alterations in intestinal microbiota structure and functional genes post-CPCM intervention, proteomic analysis detected changes in protein expression profiles related to glucose and lipid metabolism in mice, and Caco-2 cells were used for in vitro validation to clarify the regulatory effect of exopolysaccharides (EPS) (the active component of CPCM) on the PPAR\u03b3-LXR\u03b1-NPC1L1 signaling pathway. Results: The results showed that CPCM significantly improved glucose and lipid metabolism and remodeled the intestinal flora structure in mice, markedly enriching beneficial bacteria such as Lactobacillus and Akkermansia and enhancing the expression of functional genes related to the peroxisome proliferator-activated receptor (PPAR) signaling pathway and short-chain fatty acid synthesis in the microbiota. Proteomic analysis revealed that CPCM reversed the expression of key proteins involved in fatty acid oxidation and transport, thereby restoring the function of the PPAR signaling pathway. In vitro experiments validated that extracellular polysaccharides, the active component of CPCM, significantly upregulated the expression of PPAR\u03b3 and liver X receptor \u03b1 (LXR\u03b1) and inhibited the expression of Niemann\u2013Pick C1-Like 1 (NPC1L1), a cholesterol absorption transporter, in Caco-2 cells. Conclusions: In conclusion, CPCM ameliorates glucose and lipid metabolic disorders in T2DM through multiple mechanisms: reshaping the intestinal probiotic community, enhancing its beneficial metabolic functions, restoring the activity of the PPAR\u03b3-LXR\u03b1 signaling pathway, and subsequently downregulating NPC1L1.<\/jats:p>","DOI":"10.3390\/metabo16030157","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T08:31:19Z","timestamp":1772181079000},"page":"157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanistic Insights into Lactobacillus harbinensis and Other Probiotics Regulating Lipid Metabolism in T2DM Mice via the PPAR\u03b3-LXR\u03b1-NPC1L1 Signaling Pathway Based on Multi-Omics Analysis"],"prefix":"10.3390","volume":"16","author":[{"given":"Baheban","family":"Yeerjiang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumchi 830017, China"},{"name":"Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumchi 830017, China"},{"name":"Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumchi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabusi","family":"Manaer","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumchi 830017, China"},{"name":"Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumchi 830017, China"},{"name":"Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumchi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelian","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumchi 830017, China"},{"name":"Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumchi 830017, China"},{"name":"Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumchi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reziya","family":"Bieerdimulati","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumchi 830017, China"},{"name":"Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumchi 830017, China"},{"name":"Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumchi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Nabi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumchi 830017, China"},{"name":"Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumchi 830017, China"},{"name":"Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumchi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Diabetes Collaborators (2023). 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