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The emerging field of the disc microbiome challenges traditional views of disc sterility, which opens new avenues for novel clinical insights. However, the lack of methodological consensus in disc microbiome studies introduces discrepancies. The aims of this study were to (1) compare the disc microbiome of non-Modic (nonMC), Modic type 1 change (MC1), and MC2 discs to findings from prior disc microbiome studies, and (2) investigate if discrepancies to prior studies can be explained with bioinformatic variations.


Sequencing of 16S rRNA in 70 discs (24 nonMC, 25 MC1, and 21 MC2) for microbiome profiling. The experimental setup included buffer contamination controls and was performed under aseptic conditions. Methodology and results were contrasted with previous disc microbiome studies. Critical bioinformatic steps that were different in our best-practice approach and previous disc microbiome studies (taxonomic lineage assignment, prevalence cut-off) were varied and their effect on results were compared.


There was limited overlap of results with a previous study on MC disc microbiome. No bacterial genera were shared using the same bioinformatic parameters. Taxonomic lineage assignment using “amplicon sequencing variants” was more sensitive and detected 48 genera compared to 22 with “operational taxonomic units” (previous study). Increasing filter cut-off from 4% to 50% (previous study) reduced genera from 48 to 4 genera. Despite these differences, both studies observed dysbiosis with an increased abundance of gram-negative bacteria in MC discs as well as a lower beta-diversity. Cutibacterium was persistently detected in all groups independent of the bioinformatic approach, emphasizing its prevalence.


There is dysbiosis in MC discs. Bioinformatic parameters impact results yet cannot explain the different findings from this and a previous study. Therefore, discrepancies are likely caused by different sample preparations or true biologic differences. Harmonized protocols are required to advance understanding of the disc microbiome and its clinical implications.

All Publications

The role of the complement system in disc degeneration and Modic changes

Bone marrow stromal cells in Modic type 1 changes promote neurite outgrowth

Mengis T, Herger N, Heggli I, Devan J, Spirig JM, Laux CJ, Brunner F, Farshad M, Distler O, Dudli S.

Front Cell Dev Biol. 2023 Oct 25;11:1286280. doi: 10.3389/fcell.2023.1286280. eCollection 2023. PMID: 37965581

Cartilaginous endplates: A comprehensive review on a neglected structure in intervertebral disc research

Crump KB, Alminnawi A, Bermudez-Lekerika P, Compte R, Gualdi F, McSweeney T, Muñoz-Moya E, Nüesch A, Geris L, Dudli S, Karppinen J, Noailly J, Le Maitre C, Gantenbein B.

JOR Spine. 2023 Oct 21. DOI: 10.1002/jsp2.1294. eCollection 2023 Dec.

Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates

The role of the bone in complex regional pain syndrome 1-A systematic review

Gil KollmannMaria M Wertli, Stefan DudliOliver DistlerFlorian Brunner

Eur J Pain​. 2023 Mar 31. DOI: 10.1002/ejp.2116. Online ahead of print.

Harmonization and Standardization of Nucleus pulposus Cell Culture Methods.

Basatvat S, Binch ALA, Snuggs J, Owen D, Williams R, Richardson SM, Hoyland JA, Gansau J, Buckley CT, Glaeser JD, Sheyn D, Wang D, Vo N , Jacobsen T, Chahine NO, Presciutti SM, Drissi H, Yoon T, Illien-Junger S, Gawri R, Lang G, Hernandez PA, Fearing BV, Setton LA, Dudli S, Schol J, Sakai D, Guerrero J, Gantenbein B, Li Z, Peroglio M, Grad S, Kraus P, Lufkin T, O'Connell GD, Dahia C, Kaito T, Kushioka J, Wachs RA, DiStefano T, Panebianco C, Iatridis JC, Bowles RD, Sun Y, Leung VY, Haglund L, Mizuno S, Huang CY, Alvarez-Garcia O, Silverman L, Li X, Garcia JP, Creemers LB, Ito K, Medzikovic A, van Maanen JC, Laagland LT, Bach FC, Tryfonidou MA, L. Le Maitre C.

JOR Spine. e1238, DOI: 10.1002/jsp2.1238

FGF2 overrides key pro-fibrotic features of bone marrow stromal cells isolated from Modic type 1 change patients

I Heggli, U Blache, N Herger, T Mengis, PK Jaeger, R Schuepbach, N Farshad-Amacker, F Brunner, JG Snedeker, M Farshad, O Distler, S Dudli

European Cells and Materials Vol. 44 2022 (pages 101-114) DOI: 10.22203/eCM.v044a07

Protocol for Biospecimen Collection and Analysis within the BACPAC Research Program.

Fields AJ, Dudli S, Schrepf A, Kim A, Pham B, Gallego E, Mendoza S, Meropol SB, Darwin J, Sowa G, Vo NV.

Pain Med. 2022 Dec 16:pnac197. doi: 10.1093/pm/pnac197. Online ahead of print.

PMID: 36525387

Role of C-reactive protein in the bone marrow of Modic type 1 changes.

Dudli S, Heggli I, Laux CJ, Spirig JM, Wanivenhaus F, Betz M, Germann C, Farshad-Amacker NA, Herger N, Mengis T, Brunner F, Farshad M, Distler O.J Orthop Res. 2022

Sep 5. doi: 10.1002/jor.25437. Online ahead of print.

PMID: 36062874

CD90-positive stromal cells associate with inflammatory and fibrotic changes in modic changes.

Dudli S, Karol A, Giudici L, Heggli I, Laux CJ, Spirig JM, Wanivenhaus F, Betz M, Germann C, Farshad-Amacker N, Brunner F, Distler O, Farshad M.Osteoarthr Cartil Open. 2022 Jun 22;4(3):100287. doi: 10.1016/j.ocarto.2022.100287. eCollection 2022 Sep.

PMID: 36474945

Intervertebral disc cell chondroptosis elicits neutrophil response in Staphylococcus aureus spondylodiscitis.

Schweizer TA, Andreoni F, Acevedo C, Scheier TC, Heggli I, Maggio EM, Eberhard N, Brugger SD, Dudli S, Zinkernagel AS.

Front Immunol. 2022 Jul 28;13:908211. doi: 10.3389/fimmu.2022.908211. eCollection 2022.

PMID: 35967370

Should Degenerated Intervertebral Discs of Patients with Modic Type 1 Changes Be Treated with Mesenchymal Stem Cells?

Herger N, Bermudez-Lekerika P, Farshad M, Albers CE, Distler O, Gantenbein B, Dudli S.

Int J Mol Sci. 2022 Feb 28;23(5):2721. doi: 10.3390/ijms23052721.

PMID: 35269863

Development of a standardized histopathology scoring system for intervertebral disc degeneration in rat models: An initiative of the ORS spine section.

Lai A, Gansau J, Gullbrand SE, Crowley J, Cunha C, Dudli S, Engiles JB, Fusellier M, Goncalves RM, Nakashima D, Okewunmi J, Pelletier M, Presciutti SM, Schol J, Takeoka Y, Yang S, Yurube T, Zhang Y, Iatridis JC.

JOR Spine. 2021 May 26;4(2):e1150. doi: 10.1002/jsp2.1150. eCollection 2021 Jun.

PMID: 34337335

Karppinen J, Koivisto K, Ketola J, Haapea M, Paananen M, Herzig KH, Alini M, Lotz J, Dudli S, Samartzis D, Risteli J, Majuri ML, Alenius H, Kyllönen E, Järvinen J, Niinimäki J, Grad S.

Eur Spine J. 2021 Apr;30(4):1018-1027. doi: 10.1007/s00586-020-06713-z. Epub 2021 Jan 9.

PMID: 33423134

Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes

Capoor MN, Konieczna A, McDowell A, Ruzicka F, Smrcka M, Jancalek R, Maca K, Lujc M, Ahmed FS, Birkenmaier C, Dudli S, Slaby O.

Int J Mol Sci. 2021 Feb 26;22(5):2347. doi: 10.3390/ijms22052347.

PMID: 33652921

Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes).

Dudli S, Ballatori A, Bay-Jensen AC, McCormick ZL, O'Neill CW, Demir-Deviren S, Krug R, Heggli I, Juengel A, Karppinen J, Brunner F, Farshad M, Distler O, Lotz JC, Fields AJ.

Int J Mol Sci. 2020 May 27;21(11):3791. doi: 10.3390/ijms21113791.

PMID: 32471173

The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging.

Koivisto K, Karppinen J, Haapea M, Järvinen J, Kyllönen E, Tervonen O, Niinimäki J, Alini M, Lotz J, Dudli S, Samartzis D, Risteli J, Majuri ML, Alenius H, Grad S.

Diagnostics (Basel). 2019 Dec 4;9(4):212. doi: 10.3390/diagnostics9040212.

PMID: 31817123

Pulsed electromagnetic fields reduce acute inflammation in the injured rat-tail intervertebral disc.

Chan AK, Tang X, Mummaneni NV, Coughlin D, Liebenberg E, Ouyang A, Dudli S, Lauricella M, Zhang N, Waldorff EI, Ryaby JT, Lotz JC.

JOR Spine. 2019 Dec 2;2(4):e1069. doi: 10.1002/jsp2.1069. eCollection 2019 Dec.

PMID: 31891118

Quantification of Propionic Acid in the Bovine Spinal Disk After Infection of the Tissue With Propionibacteria acnes Bacteria.

Magnitsky S, Dudli S, Tang X, Kaur J, Diaz J, Miller S, Lotz JC.

Spine (Phila Pa 1976). 2018 Jun 1;43(11):E634-E638. doi: 10.1097/BRS.0000000000002448.

PMID: 29019804

Modic type 1 change is an autoimmune response that requires a proinflammatory milieu provided by the 'Modic disc'.

Dudli S, Liebenberg E, Magnitsky S, Lu B, Lauricella M, Lotz JC.

Spine J. 2018 May;18(5):831-844. doi: 10.1016/j.spinee.2017.12.004. Epub 2017 Dec 15.

PMID: 29253635

Inflammatory response of disc cells against Propionibacterium acnes depends on the presence of lumbar Modic changes.

Dudli S, Miller S, Demir-Deviren S, Lotz JC.

Eur Spine J. 2018 May;27(5):1013-1020. doi: 10.1007/s00586-017-5291-4. Epub 2017 Sep 7.

PMID: 28884220

Machine Learning-Based Classification of 38 Years of Spine-Related Literature Into 100 Research Topics.

Sing DC, Metz LN, Dudli S.

Spine (Phila Pa 1976). 2017 Jun 1;42(11):863-870. doi: 10.1097/BRS.0000000000002079.

PMID: 28125523

ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes.

Dudli S, Sing DC, Hu SS, Berven SH, Burch S, Deviren V, Cheng I, Tay BKB, Alamin TF, Ith MAM, Pietras EM, Lotz JC.

Eur Spine J. 2017 May;26(5):1362-1373. doi: 10.1007/s00586-017-4955-4. Epub 2017 Jan 31.

PMID: 28138783

Dudli S, Fields AJ, Samartzis D, Karppinen J, Lotz JC.

Eur Spine J. 2016 Nov;25(11):3723-3734. doi: 10.1007/s00586-016-4459-7. Epub 2016 Feb 25.

PMID: 26914098

Propionibacterium acnes infected intervertebral discs cause vertebral bone marrow lesions consistent with Modic changes.

Dudli S, Liebenberg E, Magnitsky S, Miller S, Demir-Deviren S, Lotz JC.

J Orthop Res. 2016 Aug;34(8):1447-55. doi: 10.1002/jor.23265. Epub 2016 Aug 3.

PMID: 27101067 

Dudli S, Ferguson SJ, Haschtmann D.

Spine J. 2014 Jul 1;14(7):1256-64. doi: 10.1016/j.spinee.2013.07.488. Epub 2014 Feb 28.

PMID: 24583791 

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