{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:40:33Z","timestamp":1793400033361,"version":"4.5.0"},"reference-count":227,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dalian Medical University Interdisciplinary Research Cooperation Project Team","award":["JCHZ2023003"],"award-info":[{"award-number":["JCHZ2023003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gut microbiota dysbiosis is intricately linked to metabolic disorders such as obesity, type 2 diabetes mellitus (T2DM), hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD). Traditional Chinese medicine (TCM), particularly when combined with probiotic fermentation, offers a promising therapeutic strategy by modulating microbial balance and host metabolism. This narrative review synthesizes current research on probiotic-fermented herbal bioactives, focusing on their mechanisms in ameliorating metabolic diseases. Probiotic and bioactive compounds (e.g., berberine, polysaccharides) are highlighted for their roles in enhancing intestinal barrier function, regulating microbial metabolites like short-chain fatty acids (SCFAs), and reducing inflammation. Fermentation techniques improve the bioavailability of TCM components while reducing toxicity, as seen in fermented Salvia miltiorrhiza and Rhizoma Coptidis. Despite promising results, challenges include the complexity of microbiota\u2013host interactions and variability in TCM standardization. Future directions emphasize integrating multi-omics technologies and personalized approaches to optimize probiotic-fermented TCM therapies. This review underscores the potential of combining traditional herbal wisdom with modern biotechnology to address metabolic disorders, which pose significant global health challenges, through a \u201cgut microbiota\u2013metabolism\u201d axis. Emerging evidence highlights the critical role of gut microbiota dysbiosis in the pathogenesis of these conditions. TCM has shown promise in modulating gut microbiota to restore metabolic homeostasis. This review synthesizes current research on TCM-derived interventions, such as herbal compounds, probiotics, and fermentation techniques, that target gut microbiota to ameliorate metabolic disorders. We discuss mechanisms of action, including prebiotic effects, enhancement of intestinal barrier function, and regulation of microbial metabolites, while addressing the limitations and future directions of TCM-based therapies.<\/jats:p>","DOI":"10.3390\/ijms26125486","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:46:01Z","timestamp":1749451561000},"page":"5486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Gut Microbiota-Targeted Therapeutics for Metabolic Disorders: Mechanistic Insights into the Synergy of Probiotic-Fermented Herbal Bioactives"],"prefix":"10.3390","volume":"26","author":[{"given":"Yue","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian 116041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8985-6769","authenticated-orcid":false,"given":"Yinhui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian 116041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyi","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian 116041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian 116041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian 116041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, College of Stomatology, Dalian Medical University, Dalian 116041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9553-5611","authenticated-orcid":false,"given":"Li","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian 116041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.cmet.2023.02.003","article-title":"The global burden of metabolic disease: Data from 2000 to 2019","volume":"35","author":"Chew","year":"2023","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. 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