{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:50:18Z","timestamp":1785408618882,"version":"3.56.0"},"reference-count":118,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007957","name":"Chongqing Municipality Education Commission","doi-asserted-by":"publisher","award":["KJQN202401144"],"award-info":[{"award-number":["KJQN202401144"]}],"id":[{"id":"10.13039\/501100007957","id-type":"DOI","asserted-by":"publisher"}]},{"award":["KJQN202401144"],"award-info":[{"award-number":["KJQN202401144"]}],"id":[{"id":"https:\/\/ror.org\/031nm5713","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Chongqing Municipal Science and Technology Commission General Programme","award":["CSTB2025NSCQ-GPX0230"],"award-info":[{"award-number":["CSTB2025NSCQ-GPX0230"]}]},{"DOI":"10.13039\/501100004867","name":"Chongqing University of Technology","doi-asserted-by":"crossref","award":["gzlcx20233379"],"award-info":[{"award-number":["gzlcx20233379"]}],"id":[{"id":"10.13039\/501100004867","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004867","name":"Chongqing University of Technology","doi-asserted-by":"crossref","award":["gzlcx20253283"],"award-info":[{"award-number":["gzlcx20253283"]}],"id":[{"id":"10.13039\/501100004867","id-type":"DOI","asserted-by":"crossref"}]},{"award":["gzlcx20233379"],"award-info":[{"award-number":["gzlcx20233379"]}],"id":[{"id":"https:\/\/ror.org\/04vgbd477","id-type":"ROR","asserted-by":"publisher"}]},{"award":["gzlcx20253283"],"award-info":[{"award-number":["gzlcx20253283"]}],"id":[{"id":"https:\/\/ror.org\/04vgbd477","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Metabolic diseases, including obesity, type 2 diabetes, and their related complications, have emerged as major global public health challenges. Increasing evidence indicates that gut microbiota dysbiosis contributes to disrupted metabolic homeostasis, chronic low-grade inflammation, and progression of metabolic disorders. Among candidate microbiome-based interventions, Lactiplantibacillus plantarum (L. plantarum) and Akkermansia muciniphila (A. muciniphila) have attracted particular attention because they regulate host metabolism through partially distinct yet potentially complementary mechanisms. L. plantarum has been associated with modulation of appetite-related hormones, adipose tissue remodeling, reinforcement of intestinal barrier function, and attenuation of inflammatory signaling. A. muciniphila has been linked to strengthening of the mucus barrier, production of beneficial metabolites, and improvement in immune and metabolic homeostasis. However, current evidence remains fragmented across strain-specific studies, heterogeneous formulations, and predominantly single-strain experimental designs, and direct comparative evidence for combined administration is still limited. This review synthesizes current epidemiological, mechanistic, preclinical, and clinical evidence on L. plantarum and A. muciniphila, with emphasis on their physiological traits, gut ecological adaptability, pathway-based metabolic effects, and translational challenges in obesity, type 2 diabetes, and related complications. We further highlight the ecological rationale for their functional complementarity and discuss priorities for future combination studies and precision implementation. Overall, the available literature supports functional complementarity and possible additive metabolic benefits, but synergistic effects in humans remain unconfirmed. A clearer understanding of strain identity, active therapeutic entities, delivery strategies, and host context will be essential for advancing this dual-target microbial strategy toward clinically meaningful applications.<\/jats:p>","DOI":"10.3390\/metabo16040259","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:49:02Z","timestamp":1776070142000},"page":"259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Dual-Target Microbial Therapeutic Strategy for Treating Metabolic Diseases: Complementary Mechanisms and Clinical Prospects of Lactiplantibacillus plantarum and Akkermansia muciniphila"],"prefix":"10.3390","volume":"16","author":[{"given":"Si","family":"Liu","sequence":"first","affiliation":[{"name":"College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Sun","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5525-2721","authenticated-orcid":false,"given":"Zhihao","family":"Jia","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Cambridge-Suda Genomic Resource Center, Suzhou Medical College, Soochow University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuilong","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22584","DOI":"10.1038\/s41598-025-07111-5","article-title":"Lactiplantibacillus plantarum Lp05 Protects against Ethanol-Induced Liver Injury in Zebrafish through Metabolic and Microbiota Modulation","volume":"15","author":"Fan","year":"2025","journal-title":"Sci. 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