{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:34:02Z","timestamp":1790800442945,"version":"4.1.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>\n                    Metabolic syndrome (MetS) represents an escalating global health burden, underscoring an urgent need for innovative microbiome-targeted therapeutics. This investigation involved a systematic functional evaluation of 42 pasteurized\n                    <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    strains, providing the first direct evidence of significant differences among strains in their ability to alleviate MetS. Through systematic screening using cell and mouse models, we identified strain\n                    <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    YGMCC2645 (AKK2645) emerged as the lead candidate. Furthermore, it demonstrated superior and reproducible efficacy in attenuating diet-induced obesity, restoring glucose homeostasis, and ameliorating hepatic steatosis. AKK2645 uniquely modulated host immunity, decreasing pro-inflammatory cytokines (IL-6, IL-1\u03b2) and increasing anti-inflammatory markers (\n                    <jats:italic>Il4<\/jats:italic>\n                    ,\n                    <jats:italic>Il10<\/jats:italic>\n                    , and\n                    <jats:italic>Foxp3<\/jats:italic>\n                    ) in both adipose and hepatic tissues. It also favorably altered gut microbiota (increasing\n                    <jats:italic>Akkermansia<\/jats:italic>\n                    , L\n                    <jats:italic>actobacillus<\/jats:italic>\n                    ,and\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    ) and activated intestinal GLP-1 signaling. Collectively, these findings establish strain-specific functional heterogeneity as a fundamental principle governing postbiotic efficacy and identify AKK2645 as a high-potency, precision postbiotic for MetS intervention.\n                  <\/jats:p>","DOI":"10.3389\/fnut.2026.1908600","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T05:32:52Z","timestamp":1785994372000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Unveiling functional heterogeneity in pasteurized Akkermansia muciniphila identifies AKK2645 as a superior postbiotic for metabolic syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Yaqiong","family":"Li","sequence":"first","affiliation":[{"name":"Hunan Province Directly Affiliated TCM Hospital","place":["Zhuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfang","family":"Song","sequence":"additional","affiliation":[{"name":"Langfang Hotgen Biotechnology Inc.","place":["Langfang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Liu","sequence":"additional","affiliation":[{"name":"Langfang Hotgen Biotechnology Inc.","place":["Langfang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Health Examination Center, Shaanxi Provincial People\u2019s Hospital","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linbo","family":"Li","sequence":"additional","affiliation":[{"name":"Health Management Center, The Second People\u2019s Hospital of Hunan Province","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Langfang Hotgen Biotechnology Inc.","place":["Langfang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaige","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Clinical Laboratory, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"640","DOI":"10.3390\/nu15030640","article-title":"New advances in metabolic syndrome, from prevention to treatment: the role of diet and food","volume":"15","author":"Ambroselli","year":"2023","journal-title":"Nutrients"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.14309\/ajg.0000000000002730","article-title":"Role of the intestine and its gut microbiota in metabolic syndrome and obesity","volume":"119","author":"Busch","year":"2024","journal-title":"Am J Gastroenterol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2358","DOI":"10.3390\/foods14132358","article-title":"The role of inactivation methods in shaping Postbiotic composition and modulating bioactivity: a review","volume":"14","author":"Zhu","year":"2025","journal-title":"Foods"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/s41575-022-00631-9","article-title":"Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms","volume":"19","author":"Cani","year":"2022","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1984104","DOI":"10.1080\/19490976.2021.1984104","article-title":"Akkermansia Muciniphila: is it the holy grail for ameliorating metabolic diseases?","volume":"13","author":"Yan","year":"2021","journal-title":"Gut Microbes"},{"key":"ref6","doi-asserted-by":"publisher","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":"ref7","doi-asserted-by":"publisher","first-page":"574","DOI":"10.3390\/bioengineering11060574","article-title":"The recombinant Lactobacillus strains with the surface-displayed expression of Amuc_1100 ameliorate obesity in high-fat diet-fed adult mice","volume":"11","author":"Zhang","year":"2024","journal-title":"Bioengineering (Basel)"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2375555","DOI":"10.1080\/21505594.2024.2375555","article-title":"Akkermansia Muciniphila: a promising probiotic against inflammation and metabolic disorders","volume":"15","author":"Zhao","year":"2024","journal-title":"Virulence"},{"key":"ref9","doi-asserted-by":"publisher","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":"ref10","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.cmet.2024.12.010","article-title":"Akkermansia Muciniphila supplementation in patients with overweight\/obese type 2 diabetes: efficacy depends on its baseline levels in the gut","volume":"37","author":"Zhang","year":"2025","journal-title":"Cell Metab"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/nrgastro.2017.75","article-title":"Expert consensus document: the international scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics","volume":"14","author":"Gibson","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"5768","DOI":"10.1080\/10408398.2022.2158174","article-title":"Recent advances and potentiality of Postbiotics in the food industry: composition, inactivation methods, current applications in metabolic syndrome, and future trends","volume":"64","author":"Zhong","year":"2024","journal-title":"Crit Rev Food Sci Nutr"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1186\/s12864-017-4195-3","article-title":"Genome sequencing of 39 Akkermansia Muciniphila isolates reveals its population structure, genomic and functional Diverisity, and global distribution in mammalian gut microbiotas","volume":"18","author":"Guo","year":"2017","journal-title":"BMC Genomics"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1080\/19490976.2017.1279379","article-title":"Probiotics, D-lactic acidosis, oxidative stress and strain specificity","volume":"8","author":"Vitetta","year":"2017","journal-title":"Gut Microbes"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41575-021-00440-6","article-title":"The international scientific Association of Probiotics and Prebiotics (Isapp) consensus statement on the definition and scope of Postbiotics","volume":"18","author":"Salminen","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"879","DOI":"10.19813\/j.cnki.weishengyanjiu.2025.06.001","article-title":"Scientific consensus on postbiotics","volume":"6","author":"Xuesong","year":"2025","journal-title":"J Hyg Res"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1080\/19490976.2020.1737307","article-title":"Pasteurized Akkermansia Muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice","volume":"11","author":"Depommier","year":"2020","journal-title":"Gut Microbes"},{"key":"ref18","doi-asserted-by":"publisher","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":"ref19","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1007\/s12602-023-10076-4","article-title":"A next-generation Bacteria (Akkermansia Muciniphila Baa-835) presents probiotic potential against ovalbumin-induced food allergy in mice","volume":"16","author":"Miranda","year":"2024","journal-title":"Probiotics Antimicrob Proteins"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3389\/fmicb.2024.1272062","article-title":"An optimized Culturomics strategy for isolation of human Milk microbiota","volume":"15","author":"Wang","year":"2024","journal-title":"Front Microbiol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"115940","DOI":"10.1016\/j.fct.2026.115940","article-title":"Safety evaluation of pasteurized Akkermansia Muciniphila Ygmcc2645","volume":"210","author":"Tian","year":"2026","journal-title":"Food Chem Toxicol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e06780","DOI":"10.2903\/j.efsa.2021.6780","article-title":"Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to regulation (EU) 2015\/2283","volume":"19","author":"Turck","year":"2021","journal-title":"EFSA J"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"764","DOI":"10.3390\/nu14040764","article-title":"Pasteurized Akkermansia Muciniphila ameliorate the Lps-induced intestinal barrier dysfunction via modulating Ampk and Nf-\u039ab through Tlr2 in Caco-2 cells","volume":"14","author":"Shi","year":"2022","journal-title":"Nutrients"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.3390\/ijms262411877","article-title":"An Atf3 inducer ameliorates metabolic dysfunction-associated Steatotic liver disease through the Ampk and Pka pathways","volume":"26","author":"Cheng","year":"2025","journal-title":"Int J Mol Sci"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s12602-021-09851-y","article-title":"The combined effect of potential probiotic Bacillus licheniformis MCC 2514 and Bifidobacterium breve NCIM 5671 towards anti-inflammatory activity on HT-29 cell lines","volume":"15","author":"Rohith","year":"2021","journal-title":"Probiotics Antimicrob Proteins"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3160","DOI":"10.1021\/acs.jafc.7b00489","article-title":"Effects of \u0391-Galactooligosaccharides from chickpeas on high-fat-diet-induced metabolic syndrome in mice","volume":"65","author":"Dai","year":"2017","journal-title":"J Agric Food Chem"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"106099","DOI":"10.1016\/j.jff.2024.106099","article-title":"Anti-obesity effects of Bifidobacterium lactis Ygmcc2013 by promoting adipocyte thermogenesis and beige remodelling in association with gut microbiota","volume":"115","author":"He","year":"2024","journal-title":"J Funct Foods"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"40243","DOI":"10.1039\/c8ra08622b","article-title":"One-pot synthesis of 3,4-Dihydropyrimidin-2(1h)-ones catalyzed by So3h@Iminezcmnps as a novel, efficient and reusable acidic Nanocatalyst under solvent-free conditions","volume":"8","author":"Abbaspour-Gilandeh","year":"2018","journal-title":"RSC Adv"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1186\/1756-0500-7-660","article-title":"Dietary Xylo-oligosaccharide stimulates intestinal Bifidobacteria and lactobacilli but has limited effect on intestinal integrity in rats","volume":"7","author":"Christensen","year":"2014","journal-title":"BMC Res Notes"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.3390\/nu13031017","article-title":"Bifidobacterium Adolescentis isolated from different hosts modifies the intestinal microbiota and displays differential metabolic and immunomodulatory properties in mice fed a high-fat diet","volume":"13","author":"Wang","year":"2021","journal-title":"Nutrients"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e136","DOI":"10.1002\/imt2.136","article-title":"Intraspecific difference of Latilactobacillus Sakei in inflammatory bowel diseases: insights into potential mechanisms through comparative genomics and metabolomics analyses","volume":"2","author":"Liu","year":"2023","journal-title":"iMeta"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e6651","DOI":"10.7717\/peerj.6651","article-title":"Dose-dependent and strain-dependent anti-obesity effects of Lactobacillus sakei in a diet induced obese murine model","volume":"7","author":"Ji","year":"2019","journal-title":"PeerJ"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"242","DOI":"10.3389\/fmicb.2018.00242","article-title":"Intra-species genomic and physiological variability impact stress resistance in strains of probiotic potential","volume":"9","author":"Arnold","year":"2018","journal-title":"Front Microbiol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"3509","DOI":"10.1039\/c8fo00100f","article-title":"Bifidobacteria attenuate the development of metabolic disorders, with inter- and intra-species differences","volume":"9","author":"Zhu","year":"2018","journal-title":"Food Funct"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"101412","DOI":"10.1016\/j.afres.2025.101412","article-title":"Functional properties, metabolic profile and safety attributes of postbiotics from Lacticaseibacillus acidophilus and Lactiplantibacillus plantarum","volume":"5","author":"Davarzani","year":"2025","journal-title":"Appl Food Res"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e0048421","DOI":"10.1128\/Spectrum.00484-21","article-title":"The protective effects of live and pasteurized Akkermansia Muciniphila and its extracellular vesicles against Hfd\/Ccl4-induced liver injury","volume":"9","author":"Keshavarz Azizi Raftar","year":"2021","journal-title":"Microbiol Spectrum"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"102138","DOI":"10.1016\/j.anaerobe.2019.102138","article-title":"An Akkermansia Muciniphila subtype alleviates high-fat diet-induced metabolic disorders and inhibits the neurodegenerative process in mice","volume":"61","author":"Wu","year":"2020","journal-title":"Anaerobe"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41564-025-02222-1","article-title":"Navigating the duality of Akkermansia Muciniphila","volume":"11","author":"Grant","year":"2026","journal-title":"Nat Microbiol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"3227","DOI":"10.1080\/10408398.2018.1517725","article-title":"A next generation probiotic, Akkermansia Muciniphila","volume":"59","author":"Zhai","year":"2019","journal-title":"Crit Rev Food Sci Nutr"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1730714","DOI":"10.3389\/fmicb.2025.1730714","article-title":"Gut microbiota and metabolic dysregulation in polycystic ovary syndrome: effects of acupuncture as an adjunct to in vitro fertilization on gut dysbiosis, metabolism, and oocyte quality","volume":"16","author":"Liu","year":"2025","journal-title":"Front Microbiol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/jci92035","article-title":"Inflammatory mechanisms linking obesity and metabolic disease","volume":"127","author":"Saltiel","year":"2017","journal-title":"J Clin Invest"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e102160","DOI":"10.7759\/cureus.102160","article-title":"Metabolic inflammation as a common thread in cardio-endocrine diseases: toward a unified therapeutic framework","volume":"18","author":"Patil","year":"2026","journal-title":"Cureus"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1186\/s12934-021-01709-w","article-title":"Extracellular vesicles and pasteurized cells derived from Akkermansia Muciniphila protect against high-fat induced obesity in mice","volume":"20","author":"Ashrafian","year":"2021","journal-title":"Microb Cell Factories"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1017\/S000711451200116X","article-title":"Effects of heat-inactivated Lactobacillus gasseri Tmc0356 on metabolic characteristics and immunity of rats with the metabolic syndrome","volume":"109","author":"Shi","year":"2012","journal-title":"Br J Nutr"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/s41467-025-67327-x","article-title":"Prevotella copri promotes white adipose browning and ameliorates adiposity","volume":"17","author":"Liu","year":"2025","journal-title":"Nat Commun"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/nature10653","article-title":"Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis","volume":"480","author":"Nguyen","year":"2011","journal-title":"Nature"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/s41422-020-0291-z","article-title":"Targeting Immunometabolism as an anti-inflammatory strategy","volume":"30","author":"P\u00e5lsson-McDermott","year":"2020","journal-title":"Cell Res"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1172\/JCI200319246","article-title":"Obesity is associated with macrophage accumulation in adipose tissue","volume":"112","author":"Weisberg","year":"2003","journal-title":"J Clin Invest"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.molmet.2019.09.010","article-title":"Glucagon-like peptide 1 (Glp-1)","volume":"30","author":"M\u00fcller","year":"2019","journal-title":"Mol Metab"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/s42003-026-09830-5","article-title":"A selective and augmentable butyrate-Ffar2 signal circuitry programs the cellular identity of Enteroendocrine L-cells","volume":"9","author":"Hirdaramani","year":"2026","journal-title":"Commun. Biol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/s41401-023-01186-4","article-title":"Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration","volume":"45","author":"Wang","year":"2024","journal-title":"Acta Pharmacol Sin"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"142442","DOI":"10.1016\/j.ijbiomac.2025.142442","article-title":"Function and therapeutic potential of Amuc_1100, an outer membrane protein of Akkermansia Muciniphila: a review","volume":"308","author":"Wu","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"3597","DOI":"10.1039\/d1fo00115a","article-title":"The outer membrane protein Amuc_1100 of Akkermansia Muciniphila promotes intestinal 5-Ht biosynthesis and extracellular availability through Tlr2 Signalling","volume":"12","author":"Wang","year":"2021","journal-title":"Food Funct"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41564-021-00880-5","article-title":"Akkermansia Muciniphila secretes a glucagon-like Peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice","volume":"6","author":"Yoon","year":"2021","journal-title":"Nat Microbiol"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1908600\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T05:32:53Z","timestamp":1785994373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1908600\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":55,"alternative-id":["10.3389\/fnut.2026.1908600"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1908600","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]},"article-number":"1908600"}}