{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:24:42Z","timestamp":1791516282470,"version":"4.3.4"},"reference-count":144,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"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. Microbiol."],"abstract":"<jats:p>As society ages, the number of patients with spinal degenerative diseases (SDD) is increasing, posing a major socioeconomic problem for patients and their families. SDD refers to a generic term for degenerative diseases of spinal structures, including osteoporosis (bone), facet osteoarthritis (joint), intervertebral disk degeneration (disk), lumbar spinal canal stenosis (yellow ligament), and spinal sarcopenia (muscle). We propose the term \u201cgut-spine axis\u201d for the first time, given the influence of gut microbiota (GM) on the metabolic, immune, and endocrine environment in hosts through various potential mechanisms. A close cross-talk is noted between the aforementioned spinal components and degenerative diseases. This review outlines the nature and role of GM, highlighting GM abnormalities associated with the degeneration of spinal components. It also summarizes the evidence linking GM to various SDD. The gut-spine axis perspective can provide novel insights into the pathogenesis and treatment of SDD.<\/jats:p>","DOI":"10.3389\/fmicb.2023.1290858","type":"journal-article","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T21:35:11Z","timestamp":1698528911000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Gut-spine axis: a possible correlation between gut microbiota and spinal degenerative diseases"],"prefix":"10.3389","volume":"14","author":[{"given":"Tadatsugu","family":"Morimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Kakiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Esaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatsugu","family":"Tsukamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohito","family":"Yoshihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohito","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Yabuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Mawatari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1093\/ajcn\/82.2.471","article-title":"A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents","volume":"82","author":"Abrams","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.coph.2017.10.012","article-title":"The gut-brain interaction in opioid tolerance","volume":"37","author":"Akbarali","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1249\/MSS.0000000000001495","article-title":"Exercise alters gut microbiota composition and function in lean and obese humans","volume":"50","author":"Allen","year":"2018","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e38","DOI":"10.1016\/S1473-3099(19)30756-X","article-title":"Re-examining causes of surgical site infections following elective surgery in the era of asepsis","volume":"20","author":"Alverdy","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.15252\/emmm.201606531","article-title":"Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization","volume":"8","author":"Andriessen","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e90784","DOI":"10.1371\/journal.pone.0090784","article-title":"Meconium microbiome analysis identifies bacteria correlated with premature birth","volume":"9","author":"Ardissone","year":"2014","journal-title":"PLoS One"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/35046196","article-title":"Bone versus immune system","volume":"408","author":"Arron","year":"2000","journal-title":"Nature"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"S849","DOI":"10.1016\/j.jcot.2020.06.021","article-title":"Metabolic syndrome and subchondral bone alterations: the rise of osteoarthritis - a review","volume":"11","author":"Azzini","year":"2020","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature10600","article-title":"Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders","volume":"479","author":"Baker","year":"2011","journal-title":"Nature"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.maturitas.2017.06.025","article-title":"Estrogen-gut microbiome axis: physiological and clinical implications","volume":"103","author":"Baker","year":"2017","journal-title":"Maturitas"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"313627","DOI":"10.1136\/gutjnl-2016-313627","article-title":"The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level","volume":"67","author":"Barton","year":"2018","journal-title":"Gut"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"115317","DOI":"10.1016\/j.bone.2020.115317","article-title":"The role of gut microbiota in bone homeostasis","volume":"135","author":"Behera","year":"2020","journal-title":"Bone"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/j.molmet.2016.10.003","article-title":"Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals","volume":"5","author":"Benedict","year":"2016","journal-title":"Mol. Metab."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"S86","DOI":"10.1007\/s00586-003-0593-0","article-title":"Natural history of the aging spine","volume":"12","author":"Benoist","year":"2003","journal-title":"Eur. Spine J."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e001037","DOI":"10.1136\/rmdopen-2019-001037","article-title":"Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis","volume":"5","author":"Berthelot","year":"2019","journal-title":"RMD Open"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"100946","DOI":"10.1016\/j.arr.2019.100946","article-title":"Gut microbiota and osteoarthritis management: an expert consensus of the European society for clinical and economic aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (ESCEO)","volume":"55","author":"Biver","year":"2019","journal-title":"Ageing Res. Rev."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"4881","DOI":"10.1038\/s41467-019-12873-4","article-title":"Intestinal microbiome composition and its relation to joint pain and inflammation","volume":"10","author":"Boer","year":"2019","journal-title":"Nat. Commun."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.tcb.2020.07.002","article-title":"A senescence-centric view of aging: implications for longevity and disease","volume":"30","author":"Borghesan","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"E45","DOI":"10.36076\/ppj\/2019.22.E45","article-title":"Vitamin B12 as a treatment for pain","volume":"1","author":"Buesing","year":"2019","journal-title":"Pain Physician"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s40168-017-0296-0","article-title":"(dis)trust your gut: the gut microbiome in age-related inflammation, health, and disease","volume":"5","author":"Buford","year":"2017","journal-title":"Microbiome"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/dom.12157","article-title":"Metagenome and metabolism: the tissue microbiota hypothesis","volume":"15","author":"Burcelin","year":"2013","journal-title":"Diabetes Obes. Metab."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.cell.2012.12.010","article-title":"Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model","volume":"152","author":"Burd","year":"2013","journal-title":"Cells"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1073\/pnas.1322269111","article-title":"The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition","volume":"111","author":"Chang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.clim.2015.03.019","article-title":"The intestinal microbiome and skeletal fitness: connecting bugs and bones","volume":"159","author":"Charles","year":"2015","journal-title":"Clin. Immunol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S0304-3940(00)00951-4","article-title":"Intracerebroventricular infusion of leptin decreases serotonin transporter binding sites in the frontal cortex of the rat","volume":"283","author":"Charnay","year":"2000","journal-title":"Neurosci. Lett."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13018-018-1050-4","article-title":"Pelvic incidence measurement using a computed tomography data-based three-dimensional pelvic model","volume":"14","author":"Chen","year":"2019","journal-title":"J. Orthop. Surg. Res."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"2025016","DOI":"10.1080\/19490976.2021.2025016","article-title":"Human gut microbiome aging clocks based on taxonomic and functional signatures through multi-view learning","volume":"14","author":"Chen","year":"","journal-title":"Gut Microbes"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"877776","DOI":"10.3389\/fmicb.2022.877776","article-title":"Gut microbiota and bone diseases: a growing partnership","volume":"13","author":"Chen","year":"","journal-title":"Front. Microbiol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e0261353","DOI":"10.1371\/journal.pone.0261353","article-title":"The relation between the gut microbiome and osteoarthritis: a systematic review of literature","volume":"16","author":"Chisari","year":"2021","journal-title":"PLoS One"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"725","DOI":"10.3390\/biom10050725","article-title":"Metabolic and lipidomic profiling of vegetable juices fermented with various probiotics","volume":"10","author":"Chung","year":"2020","journal-title":"Biomol. Ther."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1210\/me.2014-1108","article-title":"Minireview: gut microbiota: the neglected endocrine organ","volume":"28","author":"Clarke","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1136\/gutjnl-2013-306541","article-title":"Exercise and associated dietary extremes impact on gut microbial diversity","volume":"63","author":"Clarke","year":"2014","journal-title":"Gut"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: revised European consensus on definition and diagnosis","volume":"48","author":"Cruz-Jentoft","year":"2019","journal-title":"Age Ageing"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.bone.2008.02.017","article-title":"Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis","volume":"43","author":"D\u2019Amelio","year":"2008","journal-title":"Bone"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s12038-019-9926-y","article-title":"Homeostasis and dysbiosis of the gut microbiome in health and disease","volume":"44","author":"Das","year":"2019","journal-title":"J. Biosci."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1756308","DOI":"10.1155\/2018\/1756308","article-title":"Probiotic cell-free supernatants exhibited anti-inflammatory and antioxidant activity on human gut epithelial cells and macrophages stimulated with LPS","volume":"2018","author":"De Marco","year":"2018","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"574","DOI":"10.3390\/nu12020574","article-title":"Gut-joint axis: the role of physical exercise on gut microbiota modulation in older people with osteoarthritis","volume":"12","author":"De Sire","year":"2020","journal-title":"Nutrients"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"605","DOI":"10.3389\/fendo.2020.00605","article-title":"Altered gut microbiota composition is associated with back pain in overweight and obese individuals","volume":"11","author":"Dekker Nitert","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1158\/2159-8290.CD-20-0770","article-title":"Bacterial-driven inflammation and mutant BRAF expression combine to promote murine colon tumorigenesis that is sensitive to immune checkpoint therapy","volume":"11","author":"DeStefano Shields","year":"2021","journal-title":"Cancer Discov."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"3689","DOI":"10.2147\/JPR.S389602","article-title":"Facet joint syndrome: pathophysiology, diagnosis, and treatment","volume":"15","author":"Du","year":"2022","journal-title":"J. Pain Res."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1002\/art.41210","article-title":"Identification of cartilage microbial DNA signatures and associations with knee and hip osteoarthritis","volume":"72","author":"Dunn","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e0184274","DOI":"10.1371\/journal.pone.0184274","article-title":"The effect of age on the intestinal mucus thickness, microbiota composition and immunity in relation to sex in mice","volume":"12","author":"Elderman","year":"2017","journal-title":"PLoS One"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.jpain.2021.08.006","article-title":"Reduced gut microbiome diversity in people with HIV who have distal neuropathic pain","volume":"23","author":"Ellis","year":"2022","journal-title":"J. Pain"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"20499361211027067","DOI":"10.1177\/20499361211027067","article-title":"An exercise intervention alters stool microbiota and metabolites among older, sedentary adults","volume":"8","author":"Erlandson","year":"2021","journal-title":"Ther. Adv. Infect. Dis."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1097\/BOR.0000000000000681","article-title":"The gut microbiome-joint connection: implications in osteoarthritis","volume":"32","author":"Favazzo","year":"2020","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e0255323","DOI":"10.1371\/journal.pone.0255323","article-title":"Gut microbiota alterations in response to sleep length among African-origin adults","volume":"16","author":"Fei","year":"2021","journal-title":"PLoS One"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1080\/19490976.2019.1629236","article-title":"Mechanisms and consequences of gut commensal translocation in chronic diseases","volume":"11","author":"Fine","year":"2020","journal-title":"Gut Microbes"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1093\/gerona\/glu057","article-title":"Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases","volume":"69","author":"Franceschi","year":"2014","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"3727","DOI":"10.1093\/rheumatology\/keaa847","article-title":"An association between chronic widespread pain and the gut microbiome","volume":"60","author":"Freidin","year":"2021","journal-title":"Rheumatology (Oxford)"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"61","DOI":"10.22603\/ssrr.2020-0112","article-title":"Lumbar spinal canal stenosis from the perspective of locomotive syndrome and metabolic syndrome: a narrative review","volume":"5","author":"Fujita","year":"2021","journal-title":"Spine Surg. Relat. Res."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/s41584-020-0454-9","article-title":"Revisiting the gut-joint axis: links between gut inflammation and spondyloarthritis","volume":"16","author":"Gracey","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1007\/s00586-021-07062-1","article-title":"Evidence for infection in intervertebral disc degeneration: a systematic review","volume":"31","author":"Granville Smith","year":"2022","journal-title":"Eur. Spine J."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1002\/art.41644","article-title":"Inflammasome activation in ankylosing spondylitis is associated with gut dysbiosis","volume":"73","author":"Guggino","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.joca.2018.07.020","article-title":"The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis","volume":"27","author":"Guss","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1126\/science.1122446","article-title":"Cellular senescence in aging primates","volume":"311","author":"Herbig","year":"2006","journal-title":"Science"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nrrheum.2015.158","article-title":"Does lipopolysaccharide-mediated inflammation have a role in OA","volume":"12","author":"Huang","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jbspin.2018.02.008","article-title":"Gut microbiome and bone","volume":"86","author":"Ib\u00e1\u00f1ez","year":"2019","journal-title":"Joint Bone Spine"},{"key":"ref1001","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12121247","article-title":"Modulatory Effect of Gut Microbiota on the Gut-Brain, Gut-Bone Axes, and the Impact of Cannabinoids","volume":"12","author":"Ibrahim","year":"2022","journal-title":"Metabolites."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s00776-014-0656-6","article-title":"Japanese 2011 nationwide survey on complications from spine surgery","volume":"20","author":"Imajo","year":"2015","journal-title":"J. Orthop. Sci."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"8787","DOI":"10.3748\/wjg.v21.i29.8787","article-title":"Role of the normal gut microbiota","volume":"21","author":"Jandhyala","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/s41467-017-00900-1","article-title":"The gut microbiome in atherosclerotic cardiovascular disease","volume":"8","author":"Jie","year":"2017","journal-title":"Nat. Commun."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"2944","DOI":"10.1210\/jc.2012-4262","article-title":"Oral supplementation with probiotic L. reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D: a post hoc analysis of a randomized controlled trial","volume":"98","author":"Jones","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"4628","DOI":"10.1038\/s41598-021-84031-0","article-title":"Alterations in intestinal microbiota diversity, composition, and function in patients with sarcopenia","volume":"11","author":"Kang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"224","DOI":"10.22603\/ssrr.2021-0229","article-title":"Biomarker research approach to the pathogenesis of ossification of the spinal ligament: a review","volume":"6","author":"Kawaguchi","year":"2022","journal-title":"Spine Surg. Relat. Res."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"3290","DOI":"10.3390\/nu13093290","article-title":"Gut microbiota predicts healthy late-life aging in male mice","volume":"13","author":"Ke","year":"2021","journal-title":"Nutrients"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41574-020-0335-y","article-title":"The role of cellular senescence in ageing and endocrine disease","volume":"16","author":"Khosla","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.chom.2014.02.006","article-title":"Gut microbiota promote hematopoiesis to control bacterial infection","volume":"15","author":"Khosravi","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"673708","DOI":"10.3389\/fimmu.2021.673708","article-title":"Partners in leaky gut syndrome: intestinal dysbiosis and autoimmunity","volume":"12","author":"Kinashi","year":"2021","journal-title":"Front. Immunol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/art.41142","article-title":"2019 American College of Rheumatology\/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee","volume":"72","author":"Kolasinski","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref70","first-page":"483","article-title":"Emerging role of fecal microbiota therapy in the treatment of gastrointestinal and extra-gastrointestinal diseases","volume":"66","author":"Konturek","year":"2015","journal-title":"J. Physiol. Pharmacol."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s10522-018-9785-1","article-title":"Epigallocatechin gallate suppresses premature senescence of preadipocytes by inhibition of PI3K\/Akt\/mTOR pathway and induces senescent cell death by regulation of Bax\/Bcl-2 pathway","volume":"20","author":"Kumar","year":"2019","journal-title":"Biogerontology"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.3390\/ijms21083010","article-title":"Novel insights into the pathogenesis of spinal sarcopenia and related therapeutic approaches: a narrative review","volume":"21","author":"Kuo","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"697","DOI":"10.3920\/BM2016.0207","article-title":"The effect of probiotic Lactobacillus casei Shirota on knee osteoarthritis: a randomised double-blind, placebo-controlled clinical trial","volume":"8","author":"Lei","year":"2017","journal-title":"Benef. Microbes"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.2337\/db13-1546","article-title":"Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss","volume":"63","author":"Leproult","year":"2014","journal-title":"Diabetes"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1007\/s00586-022-07152-8","article-title":"Gut-disc axis: a cause of intervertebral disc degeneration and low back pain","volume":"31","author":"Li","year":"2022","journal-title":"Eur. Spine J."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"3495173","DOI":"10.1155\/2016\/3495173","article-title":"Diet-intestinal microbiota axis in osteoarthritis: a possible role","volume":"2016","author":"Li","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"e3852","DOI":"10.1210\/clinem\/dgab492","article-title":"The association of gut microbiota with osteoporosis is mediated by amino acid metabolism: multiomics in a large cohort","volume":"106","author":"Ling","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"487751","DOI":"10.1101\/2022.04.11.487751","article-title":"Intradiscal inflammatory stimulation induces spinal pain behavior and intervertebral disc degeneration in vivo","volume":"2022","author":"Lisiewski","year":"2022","journal-title":"bioRxiv"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"570658","DOI":"10.3389\/fcimb.2020.570658","article-title":"Gut microbiota approach-a new strategy to treat Parkinson's disease","volume":"10","author":"Liu","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"3686749","DOI":"10.1155\/2020\/3686749","article-title":"The interplay between immune system and microbiota in osteoporosis","volume":"2020","author":"Locantore","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref81","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":"ref82","doi-asserted-by":"publisher","first-page":"e03757","DOI":"10.1016\/j.heliyon.2020.e03757","article-title":"Oral intake of Streptococcus thermophil us improves knee osteoarthritis degeneration: a randomized, double-blind, placebo-controlled clinical study","volume":"6","author":"Lyu","year":"2020","journal-title":"Heliyon"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s11926-020-00972-x","article-title":"Diffuse idiopathic skeletal hyperostosis (DISH) and a possible inflammatory component","volume":"23","author":"Mader","year":"2021","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"337","DOI":"10.5217\/ir.2019.00108","article-title":"Incidental benefits after fecal microbiota transplant for ulcerative colitis","volume":"18","author":"Mahajan","year":"2020","journal-title":"Intest. Res."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1177\/1352458517739975","article-title":"Serotonin: a mediator of the gut-brain axis in multiple sclerosis","volume":"24","author":"Malinova","year":"2018","journal-title":"Mult. Scler."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.joca.2019.11.006","article-title":"The innate immune response as a mediator of osteoarthritis pain","volume":"28","author":"Miller","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1097\/j.pain.0000000000001640","article-title":"Altered microbiome composition in individuals with fibromyalgia","volume":"160","author":"Minerbi","year":"2019","journal-title":"Pain"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41577-022-00727-y","article-title":"The impact of the gut microbiome on extra-intestinal autoimmune diseases","volume":"23","author":"Miyauchi","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1007\/s12016-022-08941-1","article-title":"Inflammaging and osteoarthritis","volume":"64","author":"Motta","year":"2023","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"448","DOI":"10.4329\/wjr.v7.i12.448","article-title":"Magnetic resonance imaging of the spinal marrow: basic understanding of the normal marrow pattern and its variant","volume":"7","author":"Nouh","year":"2015","journal-title":"World J. Radiol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.tem.2014.11.004","article-title":"Effects of the gut microbiota on bone mass","volume":"26","author":"Ohlsson","year":"2015","journal-title":"Trends Endocrinol. Metab."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1080\/02713683.2019.1570526","article-title":"The ocular microbiome: molecular characterisation of a unique and low microbial environment","volume":"44","author":"Ozkan","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"5389","DOI":"10.1038\/s41598-021-84724-6","article-title":"Prevalence of spine degeneration diagnosis by type, age, gender, and obesity using Medicare data","volume":"11","author":"Parenteau","year":"2021","journal-title":"Sci. Rep."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12866-015-0386-8","article-title":"Comparative analysis of gut microbiota in elderly people of urbanized towns and longevity villages","volume":"15","author":"Park","year":"2015","journal-title":"BMC Microbiol."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.3390\/microorganisms9051070","article-title":"Probiotics and amelioration of rheumatoid arthritis: significant roles of Lactobacillus casei and Lactobacillus acidophilus","volume":"9","author":"Paul","year":"2021","journal-title":"Microorganisms"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jbspin.2010.07.001","article-title":"Osteochondral plate angiogenesis: a new treatment target in osteoarthritis","volume":"78","author":"Pesesse","year":"2011","journal-title":"Joint Bone Spine"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"7026198","DOI":"10.1155\/2018\/7026198","article-title":"Gut dysbiosis and muscle aging: searching for novel targets against sarcopenia","volume":"2018","author":"Picca","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"35405","DOI":"10.1038\/srep35405","article-title":"Chronic sleep disruption alters gut microbiota, induces systemic and adipose tissue inflammation and insulin resistance in mice","volume":"6","author":"Poroyko","year":"2016","journal-title":"Sci. Rep."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.3390\/nu12051451","article-title":"Gut-muscle axis exists and may affect skeletal muscle adaptation to training","volume":"12","author":"Przew\u0142\u00f3cka","year":"2020","journal-title":"Nutrients"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3810\/pgm.2009.11.2073","article-title":"Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data","volume":"121","author":"Puenpatom","year":"2009","journal-title":"Postgrad. Med."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s00281-021-00845-0","article-title":"The gut-joint axis in spondyloarthritis: immunological, microbial, and clinical insights","volume":"43","author":"Qaiyum","year":"2021","journal-title":"Semin. Immunopathol."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nature08821","article-title":"A human gut microbial gene catalogue established by metagenomic sequencing","volume":"464","author":"Qin","year":"2010","journal-title":"Nature"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"2884","DOI":"10.1007\/s00586-022-07335-3","article-title":"Are Modic changes 'Primary infective endplatitis'?-insights from multimodal imaging of non-specific low back pain patients and development of a radiological 'Endplate infection probability score'","volume":"31","author":"Rajasekaran","year":"2022","journal-title":"Eur. Spine J."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1007\/s00586-020-06446-z","article-title":"Human intervertebral discs harbour a unique microbiome and dysbiosis determines health and disease","volume":"29","author":"Rajasekaran","year":"2020","journal-title":"Eur. Spine J."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.smrv.2016.06.009","article-title":"The shift work and health research agenda: considering changes in gut microbiota as a pathway linking shift work, sleep loss and circadian misalignment, and metabolic disease","volume":"34","author":"Reynolds","year":"2017","journal-title":"Sleep Med. Rev."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.foodres.2019.05.002","article-title":"Anti-tumor potential of cell free culture supernatant of Lactobacillus rhamnosus strains isolated from human breast milk","volume":"123","author":"Riaz Rajoka","year":"2019","journal-title":"Food Res. Int."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"1092118","DOI":"10.3389\/fcimb.2023.1092118","article-title":"Gut-joint axis: gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways","volume":"13","author":"Romero-Figueroa","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"5786","DOI":"10.3390\/ijms21165786","article-title":"Microbiota-derived metabolites in tumor progression and metastasis","volume":"21","author":"Rossi","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1007\/s00586-017-5360-8","article-title":"Inflammaging in cervical and lumbar degenerated intervertebral discs: analysis of proinflammatory cytokine and TRP channel expression","volume":"27","author":"Sadowska","year":"2018","journal-title":"Eur. Spine J."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"E340","DOI":"10.1097\/01.brs.0000263407.25009.6e","article-title":"Lumbar ligamentum flavum hypertrophy is due to accumulation of inflammation-related scar tissue","volume":"32","author":"Sairyo","year":"2007","journal-title":"Spine (Phila Pa 1976)"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/j.cell.2016.10.020","article-title":"Linking the human gut microbiome to inflammatory cytokine production capacity","volume":"167","author":"Schirmer","year":"2016","journal-title":"Cells"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"9452","DOI":"10.3390\/ijms22179452","article-title":"The human gut microbiota: a key mediator of osteoporosis and osteogenesis","volume":"22","author":"Seely","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref113","first-page":"514","article-title":"Faecal microbiota transplantation for Clostridium difficile infection resulting in a decrease in psoriatic arthritis disease activity","volume":"37","author":"Selvanderan","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"eabc4552","DOI":"10.1126\/science.abc4552","article-title":"The microbiome and human cancer","volume":"371","author":"Sepich-Poore","year":"2021","journal-title":"Science"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1007\/s12602-021-09903-3","article-title":"Emerging interrelationship between the gut microbiome and cellular senescence in the context of aging and disease: perspectives and therapeutic opportunities","volume":"14","author":"Sharma","year":"2022","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.bone.2018.11.017","article-title":"Alterations of the gut microbiome and plasma proteome in Chinese patients with adolescent idiopathic scoliosis","volume":"120","author":"Shen","year":"2019","journal-title":"Bone"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1016\/S0140-6736(99)01376-8","article-title":"Impact of sleep debt on metabolic and endocrine function","volume":"354","author":"Spiegel","year":"1999","journal-title":"Lancet"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1093\/intimm\/dxab057","article-title":"Osteoimmunology as an intrinsic part of immunology","volume":"33","author":"Takayanagi","year":"2021","journal-title":"Int. Immunol."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"87","DOI":"10.12938\/bmfh.18-006","article-title":"Effect of Bacillus subtilis C-3102 on bone mineral density in healthy postmenopausal Japanese women: a randomized, placebo-controlled, double-blind clinical trial","volume":"37","author":"Takimoto","year":"2018","journal-title":"Biosci. Microbiota Food Health"},{"key":"ref120","first-page":"84","article-title":"Exercise and immune system as modulators of intestinal microbiome: implications for the gut-muscle axis hypothesis","volume":"25","author":"Ticinesi","year":"2019","journal-title":"Exerc. Immunol. Rev."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"3603","DOI":"10.1007\/s00586-022-07429-y","article-title":"An unexpected connection: a narrative review of the associations between gut microbiome and musculoskeletal pain","volume":"31","author":"Tonelli Enrico","year":"2022","journal-title":"Eur. Spine J."},{"key":"ref122","doi-asserted-by":"publisher","first-page":"101334","DOI":"10.1016\/j.arr.2021.101334","article-title":"Senescence in tissue samples of humans with age-related diseases: a systematic review","volume":"68","author":"Tuttle","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"15882","DOI":"10.18632\/aging.103801","article-title":"Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis","volume":"12","author":"Varela-Eir\u00edn","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/s41467-019-14177-z","article-title":"Impact of commonly used drugs on the composition and metabolic function of the gut microbiota","volume":"11","author":"Vich Vila","year":"2020","journal-title":"Nat. Commun."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3389\/fphar.2020.00394","article-title":"The cross-talk between the dopaminergic and the immune system involved in schizophrenia","volume":"11","author":"Vidal","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref126","doi-asserted-by":"publisher","first-page":"606","DOI":"10.3390\/pathogens2040606","article-title":"The gastrointestinal microbiome and musculoskeletal diseases: a beneficial role for probiotics and prebiotics","volume":"2","author":"Vitetta","year":"2013","journal-title":"Pathogens"},{"key":"ref127","doi-asserted-by":"publisher","first-page":"e3450","DOI":"10.7717\/peerj.3450","article-title":"Diversity analysis of gut microbiota in osteoporosis and osteopenia patients","volume":"5","author":"Wang","year":"2017","journal-title":"PeerJ"},{"key":"ref128","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.jfda.2017.11.009","article-title":"Lactic acid bacteria-fermented product of green tea and Houttuynia cordata leaves exerts anti-adipogenic and anti-obesity effects","volume":"26","author":"Wang","year":"2018","journal-title":"J. Food Drug Anal."},{"key":"ref129","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1097\/CM9.0000000000002339","article-title":"Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases","volume":"135","author":"Wang","year":"2022","journal-title":"Chin. Med. J."},{"key":"ref130","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1080\/02841850802524485","article-title":"No evidence for presence of bacteria in modic type I changes","volume":"50","author":"Wedderkopp","year":"2009","journal-title":"Acta Radiol."},{"key":"ref131","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1002\/art.41729","article-title":"Association between gut microbiota and symptomatic hand osteoarthritis: data from the Xiangya osteoarthritis study","volume":"73","author":"Wei","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s13059-017-1271-6","article-title":"Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis","volume":"18","author":"Wen","year":"2017","journal-title":"Genome Biol."},{"key":"ref133","doi-asserted-by":"publisher","first-page":"4741","DOI":"10.2147\/DDDT.S334421","article-title":"Inhibition of lipopolysaccharide-induced inflammatory bone loss by saikosaponin D is associated with regulation of the RANKL\/RANK pathway","volume":"15","author":"Wu","year":"2021","journal-title":"Drug Des. Devel. Ther."},{"key":"ref134","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.cell.2008.09.059","article-title":"Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum","volume":"135","author":"Yadav","year":"2008","journal-title":"Cells"},{"key":"ref135","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1007\/s11914-017-0382-z","article-title":"Gut microbiome and bone: to build, destroy, or both","volume":"15","author":"Yan","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref136","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.3390\/ijms17122126","article-title":"A possible role of intestinal microbiota in the pathogenesis of ankylosing spondylitis","volume":"17","author":"Yang","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"ref137","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.joca.2012.06.006","article-title":"Accumulation of metabolic risk factors such as overweight, hypertension, dyslipidaemia, and impaired glucose tolerance raises the risk of occurrence and progression of knee osteoarthritis: a 3-year follow-up of the ROAD study","volume":"20","author":"Yoshimura","year":"2012","journal-title":"Osteoarthr. Cartil."},{"key":"ref138","doi-asserted-by":"publisher","first-page":"3018","DOI":"10.1172\/JCI128521","article-title":"The gut-bone axis: how bacterial metabolites bridge the distance","volume":"129","author":"Zaiss","year":"2019","journal-title":"J. Clin. Invest."},{"key":"ref139","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/s41584-021-00585-3","article-title":"The gut-joint axis in rheumatoid arthritis","volume":"17","author":"Zaiss","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref140","doi-asserted-by":"publisher","first-page":"7510","DOI":"10.1080\/10408398.2022.2047005","article-title":"The regulative effect and repercussion of probiotics and prebiotics on osteoporosis: involvement of brain-gut-bone axis","volume":"63","author":"Zhang","year":"","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref141","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1007\/s00774-022-01375-x","article-title":"Fecal microbiota transplantation as a promising treatment option for osteoporosis","volume":"40","author":"Zhang","year":"","journal-title":"J. Bone Miner. Metab."},{"key":"ref142","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/s41422-020-0332-7","article-title":"Interaction between microbiota and immunity in health and disease","volume":"30","author":"Zheng","year":"2020","journal-title":"Cell Res."},{"key":"ref143","doi-asserted-by":"publisher","first-page":"e1053","DOI":"10.1002\/mbo3.1053","article-title":"Effects of exercise frequency on the gut microbiota in elderly individuals","volume":"9","author":"Zhu","year":"2020","journal-title":"Microbiology"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1290858\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T21:35:16Z","timestamp":1698528916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1290858\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,27]]},"references-count":144,"alternative-id":["10.3389\/fmicb.2023.1290858"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1290858","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,27]]},"article-number":"1290858"}}