{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:24:40Z","timestamp":1791516280335,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic low back pain (LBP) is a significant global health concern, often linked to vertebral bone marrow lesions (BML), particularly fatty replacement (FR). This study aims to explore the relationship between the gut microbiome, serum metabolome, and FR in chronic LBP patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum metabolomic profiling and gut microbiome analysis were conducted in chronic LBP patients with and without FR (LBP\u2009+\u2009FR, <jats:italic>n<\/jats:italic>\u2009=\u200940; LBP, <jats:italic>n<\/jats:italic>\u2009=\u200940) and Healthy Controls (HC, <jats:italic>n<\/jats:italic>\u2009=\u200931). The study investigates alterations in branched\u2010chain amino acids (BCAAs) levels and identifies key microbial species associated with BCAA metabolism. In\u00a0vitro experiments elucidate the role of BCAAs in adipogenesis of bone marrow mesenchymal stem cells (BM\u2010MSCs) via the SIRT4 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chronic LBP patients with FR exhibit depleted BCAA levels in their serum metabolome, along with alterations in the gut microbiome. Specific microbial species, including <jats:styled-content style=\"fixed-case\"><jats:italic>Ruminococcus gnavus<\/jats:italic><\/jats:styled-content>, <jats:styled-content style=\"fixed-case\"><jats:italic>Roseburia hominis<\/jats:italic><\/jats:styled-content>, and <jats:italic>Lachnospiraceae bacterium 8 1 57FAA<\/jats:italic>, are identified as influential in BCAA metabolism and BM\u2010MSCs metabolism. In\u00a0vitro experiments demonstrate the ability of BCAAs to induce BM\u2010MSCs adipogenesis through SIRT4 pathway activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study sheds light on the intricate relationship between the disturbed gut ecosystem, serum metabolites, and FR in chronic LBP. Dysbiosis in the gut microbiome may contribute to altered BCAA degradation, subsequently promoting BM\u2010MSCs adipogenesis and FR. Understanding these interactions provides insights for targeted therapeutic strategies to mitigate chronic LBP associated with FR by restoring gut microbial balance and modulating serum metabolite profiles.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.70042","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T04:44:32Z","timestamp":1738039472000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Gut Microbiome and Metabolome Changes in Chronic Low Back Pain Patients With Vertebral Bone Marrow Lesions"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7268-557X","authenticated-orcid":false,"given":"Wentian","family":"Li","sequence":"first","affiliation":[{"name":"Spine Labs, St. George and Sutherland Clinical School University of new South Wales  Kogarah Australia"},{"name":"Gulbali Institute, School of Agricultural, Environmental and Veterinary Sciences Charles Sturt University  Wagga Wagga Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Tu","sequence":"additional","affiliation":[{"name":"Spine Labs, St. George and Sutherland Clinical School University of new South Wales  Kogarah Australia"},{"name":"Nepean Hospital Nepean Blue Mountains Local Health District  Penrith Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjian","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, the First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhirup","family":"Das","sequence":"additional","affiliation":[{"name":"Spine Labs, St. George and Sutherland Clinical School University of new South Wales  Kogarah Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotao","family":"Jiang","sequence":"additional","affiliation":[{"name":"UNSW Microbiome Research Centre, St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health The University of new South Wales  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Spinal Surgery The Third Hospital of Hebei Medical University  Shijiazhuang China"},{"name":"Hebei Joint International Research Centre for Spinal Diseases Center for Innovation &amp; Translational Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xupeng","family":"Bai","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitao","family":"Lai","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre and School of Medical Sciences University of Sydney  Sydney Australia"},{"name":"Northcott Neuroscience Laboratory ANZAC Research Institute, Concord Hospital  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Spinal Surgery The Third Hospital of Hebei Medical University  Shijiazhuang China"},{"name":"Tissue Engineering and Microfluidics Laboratory (TE&amp;M) Australian Institute for Bioengineering and Nanotechnology (AIBN), the University of Queensland  St Lucia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1037-8421","authenticated-orcid":false,"given":"Ashish D.","family":"Diwan","sequence":"additional","affiliation":[{"name":"Spine Labs, St. George and Sutherland Clinical School University of new South Wales  Kogarah Australia"},{"name":"Spine Service Department of Orthopaedic Surgery, St. George Hospital  Kogarah Australia"},{"name":"Discipline of Orthopaedic Surgery School of Medicine, The University of Adelaide &amp; The Royal Adelaide Hospital  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6232-1326","authenticated-orcid":false,"given":"Zhaomin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Spine Labs, St. George and Sutherland Clinical School University of new South Wales  Kogarah Australia"},{"name":"Department of Spine Surgery, the First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(21)00733\u20109"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2503080474"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010008\u20100770\u20102"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000261561.12944.ff"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000224167.18483.14"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2015.168"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010016\u20104459\u20107"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010020\u201000321\u20103"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201015831\u20107"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/mnh.0000000000000678"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.02.020"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.09.071"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00605"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916\u2010015\u20100267\u2010x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/brs.0000000000001383"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010022\u201007152\u20108"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24661"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2307"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1961"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A0925"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3935"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2013.139"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.07.031"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.09.038"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479\u20107364\u20105\u20105\u2010485"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2014.04.007"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u20100168\u20100"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2013.02.002"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.046"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22851"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/life13122329"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726\u2010015\u20102168\u2010x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010020\u201006446\u2010z"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201082726\u2010y"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10060950"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.2011.3153"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574\u20106941.2009.00709.x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152811794776240"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102016\u2010313321"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00713"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010021\u201001104\u2010y"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.22203\/ecm.v032a09"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1904099116"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572\u20100241.2001.03756.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102016\u2010211064"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102015\u2010309398"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax6208"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753\u20100407.12645"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb\u20102016\u20100130"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102013\u2010304833"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0021\u20109673(00)91640\u20106"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/285017a0"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555\u20100088"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01286\u201014"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010016\u20104887\u20104"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2007.04.007"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5411.143"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092\u20108674(04)00045\u20105"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/1462\u20102920.13589"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.05.012"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.03.003"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.378877"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb\u20102011\u201012\u20106\u2010r60"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2011.139"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0301\u2010472x(02)00812\u20103"}],"updated-by":[{"DOI":"10.1002\/jsp2.70074","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000}}],"container-title":["JOR SPINE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsp2.70042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T17:02:32Z","timestamp":1746464552000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jsp2.70042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/jsp2.70042"],"URL":"https:\/\/doi.org\/10.1002\/jsp2.70042","archive":["Portico"],"relation":{"correction":[{"id-type":"doi","id":"10.1002\/jsp2.70074","asserted-by":"object"}]},"ISSN":["2572-1143","2572-1143"],"issn-type":[{"value":"2572-1143","type":"print"},{"value":"2572-1143","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,27]]},"assertion":[{"value":"2024-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70042"}}