L.A. CHUPRINA, N.A. IZETOVA, U.R. ASANOVA, F.M. MAMUTOVA, R.U. AKHTEMOV

 Order of the Red Banner of Labor Medical Institute named after S.I. Georgievsky, Simferopol

 Contact details:

Chuprina L.A. — Ph. D. (Medicine), Associate Professor of the Department of Nervous Diseases and Neurosurgery

Address: 91 Strelkovaya St., Simferopol, Russian Federation, 250060, tel.: +7-978-845-78-89, e-mail: chupr76@mail.ru

 Chronic fatigue syndrome / myalgic encephalomyelitis (ME/CFS) is a heterogeneous disease with multiple manifestations. The intestinal microbiome is receiving increasing attention in various refractory diseases, including ME/CFS. This study aims to advance our understanding of the relationship between the intestinal microbiome and ME/CFS by analyzing data from various clinical studies. We searched the literature published in 4 databases (PubMed, Cochrane Library, Web of Science, and Google Scholar) prior to May 31, 2023. Our analysis included 11 clinical studies involving 553 patients with ME/CFS and 480 healthy controls. Comparative metadata analysis revealed a significant reduction in α-diversity and a marked change in β-diversity in the gut microbiome of ME/CFS patients compared to healthy controls. The ratio of Firmicutes to Bacteroides decreased by 2.3-fold, and there was also a significant reduction in the production of microbial metabolites such as acetate, butyrate, isobutyrate and some amino acids (alanine, serine and hypoxanthine) observed in ME/CFS patients. This review provides a comprehensive analysis of recent advances in understanding the role of the intestinal microbiome in patients with ME/CFS. In addition, we also highlight the potential for using several microbiome-related interventions to alleviate ME/CFS symptoms.

Key words: chronic fatigue syndrome, myalgic encephalomyelitis, intestinal microbiota, metabolites.

REFERENCES

1. Lim E.J., Ahn Y.C., Jang E.S., Lee S.W., Lee S.H., Son C.G. Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Transl. Med, 2020, vol. 18, p. 100. DOI: 10.1186/s12967-020-02269-0
2. Lim E.J., Son C.G. Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Transl. Med, 2020, vol. 18, p. 289. DOI: 10.1186/s12967-020-02455-0
3. Wirth K.J., Löhn M. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and comorbidities: linked by vascular pathomechanisms and vasoactive mediators? Medicina, 2023, vol. 59 (5), p. 978. DOI: 10.3390/medicina59050978
4. Grach S.L., Seltzer J., Chon T.Y., Ganesh R. Diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome. Mayo Clin. Proc, 2023, vol. 98, pp. 1544–1551. DOI: 10.1016/j.mayocp.2023.07.032
5. Lim D.-W., Wang J.-H. Gut microbiome: the interplay of an «invisible organ» with herbal medicine and its derived compounds in chronic metabolic disorders. J. Environ Res. Publ. Health, 2022, vol. 19 (20), p. 13076. DOI: 10.3390/ijerph192013076
6. Xiong R., Gunter C., Fleming E., Vernon S.D., Bateman L., Unutmaz D., Oh J. Multi-‘omics of gut microbiome-host interactions in short- and long-term myalgic encephalomyelitis/chronic fatigue syndrome patients. Cell Host Microbe, 2023, vol. 31 (273–287), p. e275. DOI: 10.1016/j.chom.2023.01.001
7. Chu L., Valencia I.J., Garvert D.W., Montoya J.G. Onset patterns and course of myalgic encephalomyelitis/chronic fatigue syndrome. Pediatr, 2019, vol. 7, p. 12. DOI: 10.3389/fped.2019.00012
8. Maiuolo J., Gliozzi M., Musolino V., Carresi C., Scarano F., Nucera S. et al. The contribution of gut microbiota-brain axis in the development of brain disorders. Neurosci, 2021, vol. 15, p. 616883. DOI: 10.3389/fnins.2021.616883
9. Mou Y., Du Y., Zhou L., Yue J., Hu X., Liu Y. et al. Gut microbiota interact with the brain through systemic chronic inflammation: implications on neuroinflammation, neurodegeneration, and aging. Immunol, 2022, vol. 13, p. 796288. DOI: 10.3389/fimmu.2022.796288
10. Liu L., Wang H., Chen X., Zhang Y., Zhang H., Xie P. Gut microbiota and its metabolites in depression: from pathogenesis to treatment. EBioMedicine, 2023, vol. 90, p. 104527. DOI: 10.1016/j.ebiom.2023.104527
11. Guo C., Che X., Briese T., Ranjan A., Allicock O., Yates R.A. et al. Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS. Cell Host Microbe, 2023, vol. 31, pp. 288–304.e288. DOI: 10.1016/j.chom.2023.01.004
12. Morgan X.C., Segata N., Huttenhower C. Biodiversity and functional genomics in the human microbiome. Trends Genet, 2013, vol. 29 (1), pp. 51–58. DOI: 10.1016/j.tig.2012.09.005
13. Andrioaie I.M., Duhaniuc A., Nastase E.V., Iancu L.S., Luncă C., Trofin F. et al. The role of the gut microbiome in psychiatric disorders. Microorganisms, 2022, vol. 10 (12), p. 2436. DOI: 10.3390/microorganisms10122436
14. Shan Y., Lee M., Chang E.B. The gut microbiome and inflammatory bowel diseases. Rev. Med, 2022, vol. 73, pp. 455–468. DOI: 10.1146/annurev-med-042320-021020
15. Kers J.G., Saccenti E. The power of microbiome studies: some considerations on which alpha and beta metrics to use and how to report results. Microbiol, 2022, vol. 12, p. 796025. DOI: 10.3389/fmicb.2021.796025
16. Gilbert J.A., Blaser M.J., Caporaso J.G., Jansson J.K., Lynch S.V., Knight R. Current understanding of the human microbiome. Med, 2018, vol. 24, pp. 392–400. DOI: 10.1038/nm.4517
17. Manor O., Dai C.L., Kornilov S.A., Smith B., Price N.D., Lovejoy J.C. et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Commun, 2020, vol. 11, p. 5206. DOI: 10.1038/s41467-020-18871-1
18. Li Z., Zhou J., Liang H., Ye L., Lan L., Lu F. et al. Differences in alpha diversity of gut microbiota in neurological diseases. Neurosci, 2022, vol. 16, p. 879318. DOI: 10.3389/fnins.2022.879318
19. Leite G., Pimentel M., Barlow G.M., Chang C., Hosseini A., Wang J. et al. Age and the aging process significantly alter the small bowel microbiome. Cell Rep, 2021, vol. 36, p. 109765. DOI: 10.1016/j.celrep.2021.109765
20. Su X. Elucidating the beta-diversity of the microbiome: from global alignment to local alignment. mSystems, 2021, vol. 6 (4), p. e0036321. DOI: 10.1128/msystems.00363-00321
21. Teofani A., Marafini I., Laudisi F., Pietrucci D., Salvatori S., Unida V. et al. Intestinal taxa abundance and diversity in inflammatory bowel disease patients: an analysis including covariates and confounders. Nutrients, 2022, vol. 14 (2), p. 260. DOI: 10.3390/nu14020260
22. Visconti A., Le Roy C.I., Rosa F., Rossi N., Martin T.C., Mohney R.P. et al. Interplay between the human gut microbiome and host metabolism. Commun, 2019, vol. 10, p. 4505. DOI: 10.1038/s41467-019-12476-z
23. Lupo G.F.D., Rocchetti G., Lucini L., Lorusso L., Manara E., Bertelli M. et al. Potential role of microbiome in chronic fatigue syndrome/myalgic encephalomyelits (CFS/ME). Rep, 2021, vol. 11, p. 7043. DOI: 10.1038/s41598-021-86425-6
24. Armstrong C.W., McGregor N.R., Lewis D.P., Butt H.L., Gooley P.R. The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome. Metabolomics, 2016, vol. 13, p. 8. DOI: 10.1007/s11306-016-1145-z
25. Johnson E.L., Heaver S.L., Waters J.L., Kim B.I., Bretin A., Goodman A.L. et al. Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels. Commun, 2020, vol. 11, p. 2471. DOI: 10.1038/s41467-020-16274-w
26. Huang A.A., Huang S.Y. Quantification of the effect of vitamin e intake on depressive symptoms in united states adults using restricted cubic splines. Current Develop. Nutr, 2023, vol. 7, p. 100038. DOI: 10.1016/j.cdnut.2023.100038
27. Gothandapani D., Makpol S. Effects of vitamin E on the gut microbiome in ageing and its relationship with age-related diseases: a review of the current literature. J. Mol. Sci, 2023, vol. 24 (19), p. 14667. DOI: 10.3390/ijms241914667
28. Lee J.S., Kang J.Y., Park S.Y., Hwang S.J., Bae S.J., Son C.G. Central 5-HTergic hyperactivity induces myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like pathophysiology. Transl. Med, 2024, vol. 22, p. 34. DOI: 10.1186/s12967-023-04808-x
29. Roman P., Carrillo-Trabalon F., Sanchez-Labraca N., Canadas F., Estevez A.F., Cardona D. Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? Rev. Benef. Microbes, 2018, vol. 9, pp. 603–611. DOI: 10.3920/BM2017.0125
30. Ser H.L., Letchumanan V., Goh B.H., Wong S.H., Lee L.H. The Use of fecal microbiome transplant in treating human diseases: too early for poop? Microbiol, 2021, vol. 12, p. 519836. DOI: 10.3389/fmicb.2021.519836
31. Lacerda E.M., Geraghty K., Kingdon C.C., Palla L., Nacul L. A logistic regression analysis of risk factors in ME/CFS pathogenesis. BMC Neurol, 2019, vol. 19, p. 275. DOI: 10.1186/s12883-019-1468-2
32. Fransen F., van Beek A.A., Borghuis T., Meijer B., Hugenholtz F., van der Gaast-de Jongh C. et al. The impact of gut microbiota on gender-specific differences in immunity. Immunol, 2017, vol. 8, p. 754.