Comparative analysis of microbial biomarkers in healthy individuals, treatment-naive patients, and those on disease-modifying therapy for multiple sclerosis

The gut microbiota represents a complex regulatory ecosystem that influences metabolism, immune responses, and neurovegetative functions. Alterations in its composition may contribute to chronic inflammation and the activation of autoimmune processes, suggesting a potential role of intestinal dysbiosis in the pathogenesis of multiple sclerosis (MS). Aim of the study was to investigate the microbial and endotoxin profiles in healthy individuals and patients with relapsing-remitting MS (RRMS), both treatment-naive and receiving disease-modifying therapies (DMTs).

Material and methods. The study included 42 participants divided into three independent groups: healthy controls, untreated RRMS patients (RRMS-Naive), and RRMS patients receiving DMTs (RRMS-DMT). To assess the levels of 57 microbial markers (49 bacterial, 4 fungal, 3 viral) and endotoxin, gas chromatography-mass spectrometry (GC-MS) of microbial markers was used.

Results. Patients receiving DMTs showed reduced levels of endotoxin and several bacterial markers compared to both the control and untreated groups. The most significant differences were observed between the RRMS-DMT and RRMS-Naive groups. Statistically significant differences were identified in markers such as Clostridium propionicum, Bacteroides fragilis, Prevotella spp., Streptococcus spp., Clostridium hystolyticum, among others.

Conclusions. The findings indicate an association between the clinical status of RRMS patients and the levels of microbial and endotoxin markers. GC-MS profiling of microbial markers may serve as an additional tool for evaluating systemic inflammation and therapeutic response.

1. Marcus R. What is multiple sclerosis? JAMA. 2022;328(20):2078. doi: 10.1001/jama.2022.14236

2. Clinical guidelines «Multiple Sclerosis». 2024. Available at: clck.ru/3NY4u8 [In Russian].

3. Mirza A., Forbes J.D., Zhu F., Bernstein C.N., van Domselaar G., Graham M., Waubant E., Tremlett H. The multiple sclerosis gut microbiota: a systematic review. Mult. Scler. Relat. Disord. 2020;37:101427. doi: 10.1016/j.msard.2019.101427

4. Ordoñez-Rodriguez A., Roman P., Rueda-Ruzafa L., Campos-Rios A., Cardona D. Changes in gut microbiota and multiple sclerosis: a systematic review. Int. J. Environ. Res. Public Health. 2023;20(5):4624. doi: 10.3390/ijerph20054624

5. Dunalska A., Saramak K., Szejko N. The role of gut microbiome in the pathogenesis of multiple sclerosis and related disorders. Cells. 2023;12(13):1760. doi: 10.3390/cells12131760

6. Amini M.A., Shomali N., Bakhshi A., Rezaei S., Hemmatzadeh M., Hosseinzadeh R., Eslami S., Babaie F., Aslani S., Torkamandi S., Mohammadi H. Gut microbiome and multiple sclerosis: new insights and perspective. Int. Immunopharmacol. 2020;88:107024. doi: 10.1016/j.intimp.2020.107024

7. Wagley S., Bokori-Brown M., Morcrette H., Malaspina A., D’Arcy C., Gnanapavan S., Lewis N., Popoff M.R., Raciborska D., Nicholas R., Turner B., Titball R.W. Evidence of Clostridium perfringens epsilon toxin associated with multiple sclerosis. Mult. Scler. 2019;25(5):653–660. doi: 10.1177/1352458518767327

8. Tardov M.V., Talapbek kyzy Sh., Sturov N.V., Popova E.V., Boldin A.V., Rusanova E.I., Suvorova N.N. Gut microbiota in patients with relapsing-remitting multiple sclerosis. Zhurnal nevrologii i psikhiatrii imeni Sergeya Sergeevicha Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(1):8– 15. [In Russian]. doi: 10.17116/jnevro20231230118

9. Turnbaugh P.J., Ley R.E., Hamady M., Fraser-Liggett C.M., Knight R., Gordon J.I. The human microbiome projects. Nature. 2007;449(7164):804–810. doi: 10.1038/nature06244

10. Ruan W., Engevik M.A., Spinler J.K., Versalovic J. Healthy human gastrointestinal microbiome: composition and function after a decade of exploration. Dig. Dis. Sci. 2020;65(3):695–705. doi: 10.1007/s10620-020-06118-4

11. Fung T.C., Olson C.A., Hsiao E.Y. Interactions between the microbiota, immune and nervous systems in health and disease. Nat. Neuroscience. 2017;20(2):145–155. doi: 10.1038/nn.4476

12. Xu Q., Ni J.J., Han B.X., Yan S.S., Wei X.T., Feng G.J., Zhang H., Zhang L., Li B., Pei Y.F. Causal relationship between gut microbiota and autoimmune diseases: a two-sample Mendelian randomization study. Front. Immunol. 2022;12:746998. doi: 10.3389/fimmu.2021.746998

13. Noto D., Miyake S. Gut dysbiosis and multiple sclerosis. Clin. Immunol. 2022;235:108380. doi: 10.1016/j.clim.2020.108380

14. Koh Y.H., Ratnagopal P. Multiple sclerosis with intractable vomiting and atypical area postrema lesion. Mult. Scler. Relat. Disord. 2020;45:102348. doi: 10.1016/j.msard.2020.102348

15. Levinthal D.J., Rahman A., Nusrat S., O’Leary M., Heyman R., Bielefeldt K. Adding to the burden: gastrointestinal symptoms and syndromes in multiple sclerosis. Mult. Scler. Int. 2013;2013:319201. doi: 10.1155/2013/319201

16. Osipov G.A., Zybina N.N., Rodionov G.G. Experience in the use of mass spectrometry of microbial markers in laboratory diagnostics. Meditsinskiy alfavit = Medical Аlphabet. 2013;1(3):64–67. [In Russian].

17. Sadekov T.Sh., Boyko A.N., Omarova M.A., Rogovskii V.S., Zhilenkova O.G., Zatevalov A.M., Mironov A.Yu. Evaluation of the structure of the human microbiome in multiple sclerosis in blood microbial marker concentrations. Klinicheskaya laboratornaya diagnostika = Russian Clinical Laboratory Diagnostics. 2022;67(10):600–606. [In Russian]. doi: 10.51620/0869-2084-2022-67-10-600-606

18. Boyko A.N., Melnikov M.V., Boyko O.V., Kabaeva A.R., Omarova M.A., Zhilenkova O.G., Zatevalov A.M., Rogovskii V.S. Microbiota markers level in the cerebrospinal fluid of patients with multiple sclerosis and radiologically isolated syndrome. Nevrologiya, neyropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2021;13(1S):27–30. [In Russian]. doi: 10.14412/2074-2711-2021-1S-27-30.