{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T05:40:38Z","timestamp":1793079638130,"version":"4.5.0"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006321","name":"National Institutes of Natural Sciences","doi-asserted-by":"publisher","award":["81960878"],"award-info":[{"award-number":["81960878"]}],"id":[{"id":"10.13039\/501100006321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009590","name":"Gansu Education Department","doi-asserted-by":"publisher","award":["022CYZC-52"],"award-info":[{"award-number":["022CYZC-52"]}],"id":[{"id":"10.13039\/501100009590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018554","name":"Science and Technology Program of Gansu Province","doi-asserted-by":"publisher","award":["21YF5FA017"],"award-info":[{"award-number":["21YF5FA017"]}],"id":[{"id":"10.13039\/501100018554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Osteoporosis (OP) is a prevalent age-related skeletal disease. It is marked by compromised bone strength and higher fracture risk. Emerging evidence ties gut dysbiosis to OP development. Yet, the exact role of specific commensal bacteria remains unclear. Here, we review how\n                    <jats:italic>Akkermansia muciniphila (A. muciniphila)<\/jats:italic>\n                    affects bone metabolism. This mucin-degrading bacterium acts through three well-documented mechanisms: metabolite signaling, immune modulation, and gut-bone axis crosstalk. We also discuss emerging factors, such as host metabolic status, mechanical loading, and biomaterial applications. First,\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    produces short-chain fatty acids (SCFAs: acetate, propionate, butyrate), bile-acid metabolites, and vitamin K2. These substances boost Runx2-mediated osteoblast (OB) differentiation. They also suppress NF-\u03baB-driven osteoclastogenesis. Second, the bacterium restores gut immune balance. It does so by expanding Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T (Treg) cells and shifting macrophages toward an anti-inflammatory M2 phenotype. It also down-regulates IL-6, TNF-\u03b1, and RANKL signaling, thus limiting bone resorption. Third, via the gut-bone axis,\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    -derived extracellular vesicles (EVs) and miRNAs (e.g., miR-214-3p) enter the bloodstream. They strengthen intestinal barrier integrity, regulate calcium-phosphorus balance, and reduce systemic inflammation. Findings on\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    and bone health are conflicting. Some clinical and animal studies link higher abundance to better bone mass, with depletion worsening OP. Others, however, report negative correlations between\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    levels and bone mineral density (BMD) in separate cohorts. Most data come from pre-clinical models. Long-term human studies are scarce, and no clear causal links have been established. Future research should focus on randomized controlled trials. These trials need to define strain-specific effects, optimal doses, and safety profiles. The goal is to resolve these inconsistencies and turn\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    -based approaches into precise therapies for preventing and treating OP.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2025.1665101","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T12:22:31Z","timestamp":1757938951000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Akkermansia muciniphila and osteoporosis: emerging role of gut microbiota in skeletal homeostasis"],"prefix":"10.3389","volume":"16","author":[{"given":"Yanlong","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiumei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxiang","family":"Hai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjia","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanzhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wantao","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1007\/s12602-023-10118-x","article-title":"A critical review on akkermansia muciniphila: Functional mechanisms, technological challenges, and safety issues.","volume":"16","author":"Abbasi","year":"2024","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1053\/j.gastro.2011.02.012","article-title":"Interactions between the host innate immune system and microbes in inflammatory bowel disease.","volume":"140","author":"Abraham","year":"2011","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"562","DOI":"10.3390\/nu17030562","article-title":"Health effects and therapeutic potential of the gut microbe akkermansia muciniphila.","volume":"17","author":"Aja","year":"2025","journal-title":"Nutrients"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1111\/1462-2920.13181","article-title":"Beneficial metabolic effects of selected probiotics on diet-induced obesity and insulin resistance in mice are associated with improvement of dysbiotic gut microbiota.","volume":"18","author":"Alard","year":"2016","journal-title":"Environ. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1111\/j.1365-2362.2010.02278.x","article-title":"Regulation of adipokine production in human adipose tissue by propionic acid.","volume":"40","author":"Al-Lahham","year":"2010","journal-title":"Eur. J. Clin. Invest."},{"key":"B6","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1136\/gutjnl-2014-307142","article-title":"A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased akkermansia spp. population in the gut microbiota of mice.","volume":"64","author":"Anh\u00ea","year":"2015","journal-title":"Gut"},{"key":"B7","doi-asserted-by":"publisher","first-page":"17898","DOI":"10.1038\/s41598-021-95738-5","article-title":"Comparative effects of alive and pasteurized akkermansia muciniphila on normal diet-fed mice.","volume":"11","author":"Ashrafian","year":"2021","journal-title":"Sci. Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/s41586-022-04985-7","article-title":"Akkermansia muciniphila phospholipid induces homeostatic immune responses.","volume":"608","author":"Bae","year":"2022","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1038\/s41591-019-0504-5","article-title":"Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice.","volume":"25","author":"B\u00e1rcena","year":"2019","journal-title":"Nat. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e00478-21","DOI":"10.1128\/mBio.00478-21","article-title":"Genotypic and phenotypic diversity among human isolates of akkermansia muciniphila.","volume":"12","author":"Becken","year":"2021","journal-title":"Mbio"},{"key":"B11","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1097\/MCO.0000000000000242","article-title":"Microbiota and aging.","volume":"19","author":"Bischoff","year":"2016","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"B12","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1089\/jmf.2021.K.0148","article-title":"New strains of akkermansia muciniphila and faecalibacterium prausnitzii are effective for improving the muscle strength of mice with immobilization-induced muscular atrophy.","volume":"25","author":"Byeon","year":"2022","journal-title":"J. Med. Food"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1136\/gutjnl-2019-318427","article-title":"Leaky gut: Mechanisms, measurement and clinical implications in humans.","volume":"68","author":"Camilleri","year":"2019","journal-title":"Gut"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/gutjnl-2023-331092","article-title":"Akkermansia muciniphila derived tripeptide jams the gear of sepsis, inflammation and mortality.","volume":"73","author":"Cani","year":"2024","journal-title":"Gut"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2304900","DOI":"10.1080\/19490976.2024.2304900","article-title":"Meta-analysis reveals obesity associated gut microbial alteration patterns and reproducible contributors of functional shift.","volume":"16","author":"Chanda","year":"2024","journal-title":"Gut Microbes"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2404545","DOI":"10.1002\/advs.202404545","article-title":"Microbial tryptophan metabolites ameliorate ovariectomy-induced bone loss by repairing intestinal AhR-mediated gut-bone signaling pathway.","volume":"11","author":"Chen","year":"2024","journal-title":"Adv. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e70814","DOI":"10.1096\/fj.202501689R","article-title":"Non-surgical periodontal therapy and metformin improve bone loss in obese mice with periodontitis by modulating the gut microbiota.","volume":"39","author":"Chen","year":"2025","journal-title":"FASEB J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2393756","DOI":"10.1080\/19490976.2024.2393756","article-title":"Consistent signatures in the human gut microbiome of longevous populations.","volume":"16","author":"Chen","year":"2024","journal-title":"Gut Microbes"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2211501","DOI":"10.1080\/19490976.2023.2211501","article-title":"Dietary palmitoleic acid reprograms gut microbiota and improves biological therapy against colitis.","volume":"15","author":"Chen","year":"2023","journal-title":"Gut Microbes"},{"key":"B20","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/s41576-019-0113-7","article-title":"Clinical metagenomics.","volume":"20","author":"Chiu","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1038\/nature11319","article-title":"Gut microbiota composition correlates with diet and health in the elderly.","volume":"488","author":"Claesson","year":"2012","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1093\/jbmr\/zjae119","article-title":"Goal-directed osteoporosis treatment: ASBMR\/BHOF task force position statement 2024.","volume":"39","author":"Cosman","year":"2024","journal-title":"J. Bone Miner. Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00223-017-0331-y","article-title":"Gut microbiota, immune system, and bone.","volume":"102","author":"D\u2019Amelio","year":"2018","journal-title":"Calcif. Tissue Int."},{"key":"B24","doi-asserted-by":"publisher","first-page":"104353","DOI":"10.1016\/j.micpath.2020.104353","article-title":"Diverse effects of different akkermansia muciniphila genotypes on brown adipose tissue inflammation and whitening in a high-fat-diet murine model.","volume":"147","author":"Deng","year":"2020","journal-title":"Microb. Pathogen."},{"key":"B25","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":"B26","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":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-025-10642-y","article-title":"The role of akkermansia muciniphila in disease regulation.","author":"Ding","year":"2025","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"B28","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1002\/jat.4044","article-title":"Toxicological safety evaluation of pasteurized akkermansia muciniphila.","volume":"41","author":"Druart","year":"2021","journal-title":"J. Appl. Toxicol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"6780","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":"B30","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."},{"key":"B31","doi-asserted-by":"publisher","first-page":"10224","DOI":"10.3390\/ijms221910224","article-title":"Gut microbiota and dietary factors as modulators of the mucus layer in inflammatory bowel disease.","volume":"22","author":"Fern\u00e1ndez-Tom\u00e9","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/s41584-024-01094-9","article-title":"Evidence-based guideline for the management of osteoporosis in men.","volume":"20","author":"Fuggle","year":"2024","journal-title":"Nat. Rev. Rheumatol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3390\/microorganisms6030075","article-title":"Akkermansia muciniphila in the human gastrointestinal tract: When, where, and how?","volume":"6","author":"Geerlings","year":"2018","journal-title":"Microorganisms"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3414","DOI":"10.1097\/JS9.0000000000002339","article-title":"The existing evidence for the use of extracellular vesicles in the treatment of osteoporosis: a review","volume":"111","author":"Geng","year":"2025","journal-title":"Int. J. Surg"},{"key":"B35","doi-asserted-by":"publisher","first-page":"155638","DOI":"10.1016\/j.metabol.2023.155638","article-title":"Sarcopenia, osteoporosis and frailty.","volume":"145","author":"Gielen","year":"2023","journal-title":"Metabolism"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1002\/jcsm.12964","article-title":"Gut microbes and muscle function: Can probiotics make our muscles stronger?","volume":"13","author":"Giron","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"B37","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s00281-012-0352-6","article-title":"Inflammation and colorectal cancer: Colitis-associated neoplasia.","volume":"35","author":"Grivennikov","year":"2013","journal-title":"Semin. Immunopathol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1136\/gutjnl-2014-307264","article-title":"Diets that differ in their FODMAP content alter the colonic luminal microenvironment.","volume":"64","author":"Halmos","year":"2015","journal-title":"Gut"},{"key":"B39","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/j.immuni.2023.01.033","article-title":"The gut microbiota promotes distal tissue regeneration via ROR\u03b3+ regulatory T cell emissaries.","volume":"56","author":"Hanna","year":"2023","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.semcdb.2021.06.024","article-title":"Alliances of the gut and bone axis.","volume":"123","author":"Hansen","year":"2022","journal-title":"Semin. Cell Dev. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2393270","DOI":"10.1080\/19490976.2024.2393270","article-title":"The interplay between gut microbiota, short-chain fatty acids, and implications for host health and disease.","volume":"16","author":"Hays","year":"2024","journal-title":"Gut Microbes"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e14081","DOI":"10.1111\/acel.14081","article-title":"L-arginine metabolism ameliorates age-related cognitive impairment by amuc_1100-mediated gut homeostasis maintaining.","volume":"23","author":"He","year":"2024","journal-title":"Aging Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13287-023-03317-4","article-title":"Osteoporosis treatment using stem cell-derived exosomes: a systematic review and meta-analysis of preclinical studies","volume":"14","author":"He","year":"2023","journal-title":"Stem Cell Res. Ther"},{"key":"B44","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1007\/s11926-024-01139-8","article-title":"Effect of osteoporosis treatments on osteoarthritis progression in postmenopausal women: A review of the literature.","volume":"26","author":"Ho","year":"2024","journal-title":"Curr. Rheumatol. Rep."},{"key":"B45","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1186\/s40168-024-01971-1","article-title":"Host-specific effects of eubacterium species on Rg3-mediated modulation of osteosarcopenia in a genetically diverse mouse population.","volume":"12","author":"Hong","year":"2024","journal-title":"Microbiome"},{"key":"B46","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1111\/dgd.12119","article-title":"Histone deacetylase inhibitor sodium butyrate promotes the osteogenic differentiation of rat adipose-derived stem cells.","volume":"56","author":"Hu","year":"2014","journal-title":"Dev. Growth Differ."},{"key":"B47","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1111\/jcpe.13214","article-title":"Akkermansia muciniphila reduces porphyromonas gingivalis -induced inflammation and periodontal bone destruction.","volume":"47","author":"Huck","year":"2020","journal-title":"J. Clin. Periodontol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/s41579-024-01106-1","article-title":"Akkermansia muciniphila: Biology, microbial ecology, host interactions and therapeutic potential.","volume":"23","author":"Ioannou","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1038\/s41590-022-01284-1","article-title":"Inflammation triggers ILC3 patrolling of the intestinal barrier.","volume":"23","author":"Jarade","year":"2022","journal-title":"Nat. Immunol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/ismej.2015.88","article-title":"Composition and temporal stability of the gut microbiota in older persons.","volume":"10","author":"Jeffery","year":"2016","journal-title":"ISME J."},{"key":"B51","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s13073-025-01493-x","article-title":"Microbiome-based therapeutics towards healthier aging and longevity.","volume":"17","author":"Kadyan","year":"2025","journal-title":"Genome Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2917","DOI":"10.3390\/nu12102917","article-title":"Effects of a low-fat vegan diet on gut microbiota in overweight individuals and relationships with body weight, body composition, and insulin sensitivity. A randomized clinical trial.","volume":"12","author":"Kahleova","year":"2020","journal-title":"Nutrients"},{"key":"B53","doi-asserted-by":"publisher","first-page":"4037","DOI":"10.3390\/nu16234037","article-title":"Pasteurized akkermansia muciniphila HB05 (HB05P) improves muscle strength and function: A 12-week, randomized, double-blind, placebo-controlled clinical trial.","volume":"16","author":"Kang","year":"2024","journal-title":"Nutrients"},{"key":"B54","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s40200-021-00742-1","article-title":"Assessment of fecal akkermansia muciniphila in patients with osteoporosis and osteopenia: A pilot study.","volume":"20","author":"Keshavarz Azizi, Raftar","year":"2021","journal-title":"J. Diabetes Metab. Disord."},{"key":"B55","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41575-019-0258-z","article-title":"Gut microbiota-derived metabolites as key actors in inflammatory bowel disease.","volume":"17","author":"Lavelle","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"10872","DOI":"10.1038\/ncomms10872","article-title":"Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation.","volume":"7","author":"Li","year":"2016","journal-title":"Nat. Commun."},{"key":"B57","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1002\/jbmr.4547","article-title":"Down-to-earth studies of the gut microbiome in bone health and disease.","volume":"37","author":"Li","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"2307971","DOI":"10.1002\/advs.202307971","article-title":"The brain\u2013gut\u2013bone axis in neurodegenerative diseases: Insights, challenges, and future prospects.","volume":"11","author":"Li","year":"2024","journal-title":"Adv. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e02439-21","DOI":"10.1128\/spectrum.02439-21","article-title":"Comparative genomics revealed wide intra-species genetic heterogeneity and lineage-specific genes of akkermansia muciniphila.","volume":"10","author":"Li","year":"2022","journal-title":"Microbiol. Spectrum"},{"key":"B60","doi-asserted-by":"publisher","first-page":"132415","DOI":"10.1016\/j.ijbiomac.2024.132415","article-title":"Effect of lycium barbarum polysaccharide on osteoblast proliferation and differentiation in postmenopausal osteoporosis.","volume":"271","author":"Li","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"127595","DOI":"10.1016\/j.ijbiomac.2023.127595","article-title":"Casein-phosphatidylcholine emulsifier remodels LPS-induced intestinal barrier disfunction via regulating ferroptosis and lipid metabolism.","volume":"254","author":"Lin","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"2004831","DOI":"10.1002\/advs.202004831","article-title":"Extracellular vesicles from child gut microbiota enter into bone to preserve bone mass and strength.","volume":"8","author":"Liu","year":"2021","journal-title":"Adv. Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"dmm043620","DOI":"10.1242\/dmm.043620","article-title":"Akkermansia muciniphila promotes type H vessel formation and bone fracture healing by reducing gut permeability and inflammation.","volume":"13","author":"Liu","year":"2020","journal-title":"Dis. Models Mech."},{"key":"B64","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s40168-022-01296-x","article-title":"TLR4 regulates ROR\u03b3t+ regulatory T-cell responses and susceptibility to colon inflammation through interaction with akkermansia muciniphila.","volume":"10","author":"Liu","year":"2022","journal-title":"Microbiome"},{"key":"B65","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.cell.2016.06.011","article-title":"Mapping the pairwise choices leading from pluripotency to human bone, heart, and other mesoderm cell types.","volume":"166","author":"Loh","year":"2016","journal-title":"Cell"},{"key":"B66","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41467-017-02490-4","article-title":"Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss.","volume":"9","author":"Lucas","year":"2018","journal-title":"Nat. Commun."},{"key":"B67","doi-asserted-by":"publisher","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":"B68","doi-asserted-by":"publisher","first-page":"598","DOI":"10.3390\/agriculture14040598","article-title":"Akkermansia muciniphila promotes bone development and improves eggshell quality during the sexual maturity period of laying hens by increasing osteogenesis.","volume":"14","author":"Lyu","year":"2024","journal-title":"Agriculture"},{"key":"B69","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-chain fatty acids: Linking diet, the microbiome and immunity.","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/s41579-022-00768-z","article-title":"Microbiota succession throughout life from the cradle to the grave.","volume":"20","author":"Martino","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"e942899","DOI":"10.12659\/MSM.942899","article-title":"Potential of gut microbial metabolites in treating osteoporosis and obesity: A network pharmacology and bioinformatics approach.","volume":"30","author":"Morshed","year":"2024","journal-title":"Med. Sci. Monit."},{"key":"B72","doi-asserted-by":"publisher","first-page":"e00500-20","DOI":"10.1128\/IAI.00500-20","article-title":"Akkermansia muciniphila and its pili-like protein amuc_1100 modulate macrophage polarization in experimental periodontitis.","volume":"89","author":"Mulhall","year":"2020","journal-title":"Infect. Immun."},{"key":"B73","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.3389\/fmicb.2018.02323","article-title":"Six-week endurance exercise alters gut metagenome that is not reflected in systemic metabolism in over-weight women.","volume":"9","author":"Munukka","year":"2018","journal-title":"Front. Microbiol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.chom.2023.01.006","article-title":"Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress.","volume":"31","author":"Naama","year":"2023","journal-title":"Cell Host Microbe"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1500899","DOI":"10.1002\/mnfr.201500899","article-title":"Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake, an effect related to the modulation of the gut microbiota.","volume":"61","author":"Neyrinck","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"2717","DOI":"10.1016\/j.cell.2024.03.034","article-title":"Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.","volume":"187","author":"Nie","year":"2024","journal-title":"Cell"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1126\/science.aac8469","article-title":"Gut microbiota and aging.","volume":"350","author":"O\u2019Toole","year":"2015","journal-title":"Science"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1237727","DOI":"10.3389\/fendo.2023.1237727","article-title":"A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength.","volume":"14","author":"Okoro","year":"2023","journal-title":"Front. Endocrinol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/897639","article-title":"Probiotics (bifidobacterium longum) increase bone mass density and UpregulateSparcandBmp-2Genes in rats with bone loss resulting from ovariectomy.","volume":"2015","author":"Parvaneh","year":"2015","journal-title":"Biomed Res. Int."},{"key":"B80","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41419-024-06475-2","article-title":"IL-17 promotes osteoclast-induced bone loss by regulating glutamine-dependent energy metabolism.","volume":"15","author":"Peng","year":"2024","journal-title":"Cell Death Dis."},{"key":"B81","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":"B82","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s42523-025-00409-9","article-title":"Intestinal microbiota profiles of captive-bred cynomolgus macaques reveal influence of biogeography and age.","volume":"7","author":"Purse","year":"2025","journal-title":"Anim. Microbiome"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.18632\/aging.205396","article-title":"Gut microbial community and fecal metabolomic signatures in different types of osteoporosis animal models.","volume":"16","author":"Qiao","year":"2024","journal-title":"Aging"},{"key":"B84","doi-asserted-by":"publisher","first-page":"752990","DOI":"10.3389\/fcell.2021.752990","article-title":"The relationship between osteoporosis and intestinal microbes in the henan province of China.","volume":"9","author":"Qin","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"2409936","DOI":"10.1002\/smll.202409936","article-title":"Regulating mitochondrial aging via targeting the gut-bone axis in BMSCs with oral hydrogel microspheres to inhibit bone loss.","volume":"21","author":"Qu","year":"2025","journal-title":"Small"},{"key":"B86","doi-asserted-by":"publisher","first-page":"934695","DOI":"10.3389\/fimmu.2022.934695","article-title":"Akkermansia muciniphila and gut immune system: A good friendship that attenuates inflammatory bowel disease, obesity, and diabetes.","volume":"13","author":"Rodrigues","year":"2022","journal-title":"Front. Immunol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1126\/science.aan3706","article-title":"Gut microbiome influences efficacy of PD-1\u2013based immunotherapy against epithelial tumors.","volume":"359","author":"Routy","year":"2018","journal-title":"Science"},{"key":"B88","doi-asserted-by":"publisher","first-page":"3820","DOI":"10.1038\/s41598-019-40347-6","article-title":"Intensity of nosema ceranae infection is associated with specific honey bee gut bacteria and weakly associated with gut microbiome structure.","volume":"9","author":"Rubanov","year":"2019","journal-title":"Sci. Rep."},{"key":"B89","doi-asserted-by":"publisher","first-page":"eabm6931","DOI":"10.1126\/sciimmunol.abm6931","article-title":"Epithelial HVEM maintains intraepithelial T cell survival and contributes to host protection.","volume":"7","author":"Seo","year":"2022","journal-title":"Sci. Immunol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.2147\/JIR.S448900","article-title":"Exploring core genes associated with sepsis and systemic inflammatory response syndrome using single-cell sequencing technology.","volume":"18","author":"Shen","year":"2025","journal-title":"J. Inflammation Res."},{"key":"B91","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1136\/gutjnl-2012-303839","article-title":"An increase in the akkermansia spp. Population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice.","volume":"63","author":"Shin","year":"2014","journal-title":"Gut"},{"key":"B92","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/s41586-024-07162-0","article-title":"A host-microbiota interactome reveals extensive transkingdom connectivity.","volume":"628","author":"Sonnert","year":"2024","journal-title":"Nature"},{"key":"B93","doi-asserted-by":"publisher","first-page":"eadj3502","DOI":"10.1126\/science.adj3502","article-title":"Microbiome diversity protects against pathogens by nutrient blocking.","volume":"382","author":"Spragge","year":"2023","journal-title":"Science"},{"key":"B94","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1136\/svn-2024-003494","article-title":"Bone marrow-derived mesenchymal stem cell ameliorates post-stroke enterobacterial translocation through liver-gut axis.","volume":"10","author":"Su","year":"2024","journal-title":"Stroke Vasc. Neurol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"7152","DOI":"10.1038\/s41598-024-57732-5","article-title":"Lacidophilin tablets alleviate constipation through regulation of intestinal microflora by promoting the colonization of akkermansia sps.","volume":"14","author":"Sun","year":"2024","journal-title":"Sci. Rep."},{"key":"B96","doi-asserted-by":"publisher","first-page":"2826","DOI":"10.1158\/0008-5472.CAN-08-4466","article-title":"GPR109A is a G-protein\u2013coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon.","volume":"69","author":"Thangaraju","year":"2009","journal-title":"Cancer Res."},{"key":"B97","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.chom.2019.07.004","article-title":"Obese individuals with and without type 2 diabetes show different gut microbial functional capacity and composition.","volume":"26","author":"Thingholm","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1136\/gutjnl-2024-333378","article-title":"What defines a healthy gut microbiome?","volume":"73","author":"Van Hul","year":"2024","journal-title":"Gut"},{"key":"B99","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1016\/j.cmet.2024.04.004","article-title":"Gut microbial alterations in arginine metabolism determine bone mechanical adaptation.","volume":"36","author":"Wang","year":"2024","journal-title":"Cell Metab."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1285621","DOI":"10.3389\/fimmu.2023.1285621","article-title":"The synergistic effects of polyphenols and intestinal microbiota on osteoporosis.","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Immunol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"619","DOI":"10.3390\/genes13040619","article-title":"Gut microbiota feature of senile osteoporosis by shallow shotgun sequencing using aged rats model.","volume":"13","author":"Wang","year":"2022","journal-title":"Genes"},{"key":"B102","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.3389\/fmicb.2017.01955","article-title":"Akkermansia muciniphila may determine chondroitin sulfate ameliorating or aggravating osteoarthritis.","volume":"8","author":"Wang","year":"2017","journal-title":"Front. Microbiol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.cmet.2020.06.011","article-title":"The gut microbiota in prediabetes and diabetes: A population-based cross-sectional study.","volume":"32","author":"Wu","year":"2020","journal-title":"Cell Metab."},{"key":"B104","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1136\/gutjnl-2023-329996","article-title":"Novel tripeptide RKH derived from akkermansia muciniphila protects against lethal sepsis.","volume":"73","author":"Xie","year":"2024","journal-title":"Gut"},{"key":"B105","doi-asserted-by":"publisher","first-page":"107278","DOI":"10.1016\/j.phrs.2024.107278","article-title":"Akkermansia muciniphila-derived pentadecanoic acid enhances oxaliplatin sensitivity in gastric cancer by modulating glycolysis.","volume":"206","author":"Xu","year":"2024","journal-title":"Pharmacol. Res."},{"key":"B106","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/s40168-022-01390-0","article-title":"Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling.","volume":"10","author":"Yan","year":"2022","journal-title":"Microbiome"},{"key":"B107","doi-asserted-by":"publisher","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":"B108","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1002\/med.22081","article-title":"Estrogen deficiency-mediated osteoimmunity in postmenopausal osteoporosis.","volume":"45","author":"Yao","year":"2025","journal-title":"Med. Res. Rev."},{"key":"B109","doi-asserted-by":"publisher","first-page":"10893","DOI":"10.1038\/s41467-024-55263-1","article-title":"Colon-targeted engineered postbiotics nanoparticles alleviate osteoporosis through the gut-bone axis.","volume":"15","author":"Yu","year":"2024","journal-title":"Nat. Commun."},{"key":"B110","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1007\/s10586-022-03707-y","article-title":"Popular deep learning algorithms for disease prediction: A review.","volume":"26","author":"Yu","year":"2023","journal-title":"Cluster Comput."},{"key":"B111","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.14336\/AD.2023.0325","article-title":"Potential effects of akkermansia muciniphila in aging and aging-related diseases: Current evidence and perspectives.","volume":"14","author":"Zeng","year":"2023","journal-title":"Aging Dis."},{"key":"B112","doi-asserted-by":"publisher","first-page":"2401064","DOI":"10.1002\/adfm.202401064","article-title":"Natural phenolic-metal framework strengthened mesona chinensis polysaccharides microgels for improved viability of probiotics to alleviate the liver injury and gut microbiota dysbiosis.","volume":"34","author":"Zhang","year":"","journal-title":"Adv. Funct. Mater."},{"key":"B113","doi-asserted-by":"publisher","first-page":"eadn9524","DOI":"10.1126\/science.adn9524","article-title":"A naturally isolated symbiotic bacterium suppresses flavivirus transmission by aedes mosquitoes.","volume":"384","author":"Zhang","year":"","journal-title":"Science"},{"key":"B114","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41392-023-01311-z","article-title":"Application of metabolomics in urolithiasis: The discovery and usage of succinate.","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduction Targeted Ther."},{"key":"B115","doi-asserted-by":"publisher","first-page":"7350","DOI":"10.1021\/acsnano.4c18099","article-title":"Yeast-inspired orally-administered nanocomposite scavenges oxidative stress and restores gut immune homeostasis for inflammatory bowel disease treatment.","volume":"19","author":"Zhang","year":"2025","journal-title":"ACS Nano"},{"key":"B116","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":"B117","doi-asserted-by":"publisher","first-page":"26807","DOI":"10.1021\/acsnano.4c07658","article-title":"Gastrointestinal self-adaptive and nutrient self-sufficient akkermansia muciniphila \u2013gelatin porous microgels for synergistic therapy of ulcerative colitis.","volume":"18","author":"Zhang","year":"","journal-title":"ACS Nano"},{"key":"B118","doi-asserted-by":"publisher","first-page":"102196","DOI":"10.1016\/j.arr.2024.102196","article-title":"Targeting the gut microbiota-related metabolites for osteoporosis: The inextricable connection of gut-bone axis.","volume":"94","author":"Zhang","year":"","journal-title":"Ageing Res. Rev."},{"key":"B119","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1186\/s12967-025-06426-1","article-title":"Enhancing akkermansia growth via phytohormones: A strategy to modulate the gut-bone axis in postmenopausal osteoporosis therapy.","volume":"23","author":"Zhao","year":"2025","journal-title":"J. Transl. Med."},{"key":"B120","doi-asserted-by":"publisher","first-page":"1089600","DOI":"10.3389\/fimmu.2022.1089600","article-title":"The role of akkermansia muciniphila in inflammatory bowel disease: Current knowledge and perspectives.","volume":"13","author":"Zheng","year":"2023","journal-title":"Front. Immunol."},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c07332","article-title":"Oral propolis nanoemulsions modulate gut microbiota to balance bone remodeling for enhanced osteoporosis therapy.","author":"Zheng","year":"2024","journal-title":"ACS Nano"},{"key":"B122","doi-asserted-by":"publisher","first-page":"2465587","DOI":"10.1080\/09513590.2025.2465587","article-title":"Clinical correlation between intestinal flora profiles and the incidence of postmenopausal osteoporosis.","volume":"41","author":"Zhu","year":"2025","journal-title":"Gynecol. Endocrinol."},{"key":"B123","doi-asserted-by":"publisher","first-page":"2166700","DOI":"10.1080\/19490976.2023.2166700","article-title":"Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice.","volume":"15","author":"Zhu","year":"2023","journal-title":"Gut Microbes"},{"key":"B124","doi-asserted-by":"publisher","first-page":"2409138","DOI":"10.1002\/adma.202409138","article-title":"Extracellular vesicles from nanomedicine-trained intestinal microbiota substitute for fecal microbiota transplant in treating ulcerative colitis.","volume":"36","author":"Zu","year":"2024","journal-title":"Adv. Mater."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1665101\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T12:22:33Z","timestamp":1757938953000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1665101\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":124,"alternative-id":["10.3389\/fmicb.2025.1665101"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1665101","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,15]]},"article-number":"1665101"}}