{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:59:17Z","timestamp":1775815157937,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cPioneer\u201d and \u201cLeading Goose\u201d R&D Programs of Zhejiang","award":["2025C01099"],"award-info":[{"award-number":["2025C01099"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFF1100204"],"award-info":[{"award-number":["2022YFF1100204"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiashan Science and Technology Funds","award":["2024A23"],"award-info":[{"award-number":["2024A23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Probiotics and medicine food homology are known to offer gentle approaches to prevent obesity, although it is difficult with such approaches to satisfy consumers\u2019 requirements to lose weight quickly. The probiotic strain Bifidobacterium animalis ssp. lactis 420 (B420) and Cordyceps militaris synergistically prevented obesity and related disorders in high-fat diet (HFD)-fed mice. Methods: The synergistic effects correlated with improved gut integrity, diminished systemic inflammation, and enhanced glucose homeostasis. Gut microbiota analysis revealed that the bloom of the commensal Akkermansia muciniphila contributed to the synergistic effects by inducing a profound shift in HFD-induced gut microbiota disorder. Results: The bloom of A. muciniphila was significantly correlated with a boost in mucin 2 within the colon, achieved through increased goblet cell quantity and elevated mucin 2 expression. To reveal the collaborating pathway, we found that Cordyceps militaris did not promote the propagation of B420 in vitro or in vivo. Moreover, heat-killed B420 could not enhance the preventive efficacy of Cordyceps militaris against obesity caused by the HFD. Conclusions: The metabolites of live B420 and Cordyceps militaris-derived metabolites in the gut microbiota collaboratively promoted the production of mucin 2. Thus, our results reveal a mechanism by which a combination of probiotics and medicine food homology enhance their therapeutic effects against obesity.<\/jats:p>","DOI":"10.3390\/nu18081195","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:08:12Z","timestamp":1775812092000},"page":"1195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bifidobacterium animalis ssp. lactis 420 and Cordyceps militaris Synergistically Modulate the Gut Microbiota by Increasing Mucin 2 Production"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4834-5088","authenticated-orcid":false,"given":"Ziyang","family":"Deng","sequence":"first","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Zhejiang University, 866 Yuhangtang Rd., Hangzhou 310058, China"},{"name":"Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Zhejiang University, 866 Yuhangtang Rd., Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jike","family":"Shuai","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Zhejiang University, 866 Yuhangtang Rd., Hangzhou 310058, China"},{"name":"Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miaomiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Tonicare Electronic Commerce (Hangzhou) Co., Ltd., Hangzhou 310016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Yang","sequence":"additional","affiliation":[{"name":"Tonicare Electronic Commerce (Hangzhou) Co., Ltd., Hangzhou 310016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghong","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Zhejiang University, 866 Yuhangtang Rd., Hangzhou 310058, China"},{"name":"Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingqian","family":"Ye","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Zhejiang University, 866 Yuhangtang Rd., Hangzhou 310058, China"},{"name":"Zhongyuan Institute, Zhejiang University, Zhengzhou 450007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiguo","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Zhejiang University, 866 Yuhangtang Rd., Hangzhou 310058, China"},{"name":"Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibo","family":"Pan","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Zhejiang University, 866 Yuhangtang Rd., Hangzhou 310058, China"},{"name":"Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/S0140-6736(24)01210-8","article-title":"Obesity in adults","volume":"404","author":"Lingvay","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41574-022-00794-0","article-title":"The gut microbiota in obesity and weight management: Microbes as friends or foe?","volume":"19","author":"Cani","year":"2023","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41591-019-0495-2","article-title":"Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: A proof-of-concept exploratory study","volume":"25","author":"Depommier","year":"2019","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s12223-022-00973-6","article-title":"Disease-associated dysbiosis and potential therapeutic role of Akkermansia muciniphila, a mucus degrading bacteria of gut microbiome","volume":"67","author":"Aggarwal","year":"2022","journal-title":"Folia Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.chom.2024.07.028","article-title":"Engineered probiotic ameliorates ulcerative colitis by restoring gut microbiota and redox homeostasis","volume":"32","author":"Guo","year":"2024","journal-title":"Cell Host Microbe"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Uusitupa, H.-M., Rasinkangas, P., Lehtinen, M.J., M\u00e4kel\u00e4, S.M., Airaksinen, K., Anglenius, H., Ouwehand, A.C., and Maukonen, J. (2020). Bifidobacterium animalis subsp. lactis 420 for Metabolic Health: Review of the Research. Nutrients, 12.","DOI":"10.3390\/nu12040892"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3920\/BM2018.0028","article-title":"Probiotic or synbiotic alters the gut microbiota and metabolism in a randomised controlled trial of weight management in overweight adults","volume":"10","author":"Hibberd","year":"2019","journal-title":"Benef. Microbes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ebiom.2016.10.036","article-title":"Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults\u2014Randomized Controlled Trial","volume":"13","author":"Stenman","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Fu, Y., Wang, Q., Tang, Z., Liu, G., Guan, G., and Lyu, J. (2024). Cordycepin Ameliorates High Fat Diet-Induced Obesity by Modulating Endogenous Metabolism and Gut Microbiota Dysbiosis. Nutrients, 16.","DOI":"10.3390\/nu16172859"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104467","DOI":"10.1016\/j.fbio.2024.104467","article-title":"Anti-obesity effects of the high molecular weight Cordyceps militaris polysaccharide CMP40 in high-fat diet mice","volume":"60","author":"Wu","year":"2024","journal-title":"Food Biosci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lee, B.-H., Chen, C.-H., Hsu, Y.-Y., Chuang, P.-T., Shih, M.-K., and Hsu, W.-H. (2021). Polysaccharides Obtained from Cordyceps militaris Alleviate Hyperglycemia by Regulating Gut Microbiota in Mice Fed a High-Fat\/Sucrose Diet. Foods, 10.","DOI":"10.3390\/foods10081870"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.jep.2013.10.064","article-title":"Effect of Cordyceps militaris extract and active constituents on metabolic parameters of obesity induced by high-fat diet in C58BL\/6J mice","volume":"151","author":"Kim","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/2211-5463.13930","article-title":"Effect of Cordyceps militaris extract containing cordycepin on the adipogenesis and lipolysis of adipocytes","volume":"15","author":"Kusama","year":"2025","journal-title":"FEBS Open Bio"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1136\/gutjnl-2017-315565","article-title":"Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice","volume":"68","author":"Nachbar","year":"2019","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8461","DOI":"10.1021\/ac301678z","article-title":"A Procedure for Alcian Blue Staining of Mucins on Polyvinylidene Difluoride Membranes","volume":"84","author":"Dong","year":"2012","journal-title":"Anal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"123241","DOI":"10.1016\/j.ijbiomac.2023.123241","article-title":"Cordyceps militaris polysaccharide alleviates diabetic symptoms by regulating gut microbiota against TLR4\/NF-\u03baB pathway","volume":"230","author":"Zhao","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tappia, P.S., Ramjiawan, B., and Dhalla, N.S. (2020). Obesity and Diabetes: Pathophysiology of Obesity-Induced Hyperglycemia and Insulin Resistance. Pathophysiology of Obesity-Induced Health Complications, Springer International Publishing.","DOI":"10.1007\/978-3-030-35358-2"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.drudis.2021.11.001","article-title":"Obesity and insulin resistance: Pathophysiology and treatment","volume":"27","author":"Tong","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"747","DOI":"10.4014\/jmb.2312.12031","article-title":"Diet-induced gut dysbiosis and leaky gut syndrome","volume":"34","author":"Chae","year":"2024","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1136\/gutjnl-2023-329815","article-title":"Obesity promotes a leaky gut, inflammation and pre-diabetes by lowering gut microbiota that metabolise ethanolamine","volume":"72","author":"Fang","year":"2023","journal-title":"Gut"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1136\/gutjnl-2022-327365","article-title":"A mechanism by which gut microbiota elevates permeability and inflammation in obese\/diabetic mice and human gut","volume":"72","author":"Mishra","year":"2023","journal-title":"Gut"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2020068","DOI":"10.1080\/19490976.2021.2020068","article-title":"The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: A systematic review and meta-analysis","volume":"14","author":"Koutoukidis","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9066","DOI":"10.1073\/pnas.1219451110","article-title":"Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity","volume":"110","author":"Everard","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1136\/gutjnl-2014-308778","article-title":"Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: Relationship with gut microbiome richness and ecology","volume":"65","author":"Dao","year":"2016","journal-title":"Gut"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nm.4236","article-title":"A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice","volume":"23","author":"Plovier","year":"2017","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1892441","DOI":"10.1080\/19490976.2021.1892441","article-title":"Mucin degrader Akkermansia muciniphila accelerates intestinal stem cell-mediated epithelial development","volume":"13","author":"Kim","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41522-022-00338-4","article-title":"Rational consideration of Akkermansia muciniphila targeting intestinal health: Advantages and challenges","volume":"8","author":"Luo","year":"2022","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"RP92906","DOI":"10.7554\/eLife.92906.5","article-title":"Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway","volume":"12","author":"Ma","year":"2025","journal-title":"eLife"},{"key":"ref_29","first-page":"e00503","article-title":"Breaking down barriers: Is intestinal mucus degradation by Akkermansia muciniphila beneficial or harmful?","volume":"93","year":"2025","journal-title":"Infect. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13099-024-00635-7","article-title":"The influence of Akkermansia muciniphila on intestinal barrier function","volume":"16","author":"Mo","year":"2024","journal-title":"Gut Pathog."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.chom.2017.11.003","article-title":"Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health","volume":"23","author":"Zou","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s40588-025-00246-z","article-title":"Bridging Ecology and Microbiomes: Applying Ecological Theories in Host-associated Microbial Ecosystems","volume":"12","author":"Flores","year":"2025","journal-title":"Curr. Clin. Microbiol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.ijbiomac.2019.04.020","article-title":"Advance in Cordyceps militaris (Linn) Link polysaccharides: Isolation, structure, and bioactivities: A review","volume":"132","author":"Zhang","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101503","DOI":"10.1016\/j.fbio.2021.101503","article-title":"Research progress on Cordyceps militaris polysaccharides","volume":"45","author":"Gu","year":"2022","journal-title":"Food Biosci."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/8\/1195\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:17:24Z","timestamp":1775812644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/8\/1195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["nu18081195"],"URL":"https:\/\/doi.org\/10.3390\/nu18081195","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]}}}