Title
Author
DOI
Article Type
Special Issue
Volume
Issue
Gut microbiota, probiotics, and migraine: a clinical review and meta-analysis
1Department of Neurology, Faculty of Medicine and Dentistry, Medical University of Warsaw, 01-809 Warsaw, Poland
2Doctoral School, Medical University of Warsaw, 02-097 Warsaw, Poland
DOI: 10.22514/jofph.2025.043 Vol.39,Issue 3,September 2025 pp.13-26
Submitted: 17 April 2025 Accepted: 25 June 2025
Published: 12 September 2025
*Corresponding Author(s): Olga Grodzka E-mail: olga.grodzka@wum.edu.pl
Migraine is a primary headache disorder affecting about 14% of the global population. The knowledge about migraine pathophysiology is increasing constantly; however, there are still many unknowns and uncertainties. Intestinal microbiota builds the gut environment together with metabolites and the immune system. Its connections with disorders outside the digestive system have been described, mainly neuropsychiatric diseases, due to the existence of the microbiota-gut-brain axis. Therefore, it is suggested that migraine is also correlated with changes in the microbiome. The review aimed to summarize the available literature related to the topic. We performed an electronic article search through the Embase Database and PubMed Database, and included 14 articles after analysis under the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. Subsequently, a meta-analysis of randomized controlled clinical trials summarizing probiotics’ effect on migraine prevention was conducted based on the same guidelines and resulted in including 2 adequate trials. Microbiome alterations have been observed in migraine patients with an influence on clinical presentation. Preclinical studies suggested a direct connection between migraine and microbiome changes. The meta-analysis has shown the influence of probiotics on migraine frequency (p = 0.003; Hedges’ g = 1.22; standard error (SE) = 0.41), and no impact on migraine severity (p = 0.069; Hedges’ g = 1.10; SE = 0.61) and attacks’ duration (p = 0.149; Hedges’ g = 0.18; SE = 0.15). However, the former was close to the statistical significance. The following work demonstrates a correlation between migraine and microbiome, which has a putative positive impact on migraine management. Moreover, probiotic supplementation can alleviate migraine symptoms. However, the main limitation is the limited number of studies, together with high heterogeneity and limited methodological consistency in the meta-analysis.
Gut microbiota; Intestinal microbiota; Microbiome; Migraine; Probiotics
Olga Grodzka,Izabela Domitrz. Gut microbiota, probiotics, and migraine: a clinical review and meta-analysis. Journal of Oral & Facial Pain and Headache. 2025. 39(3);13-26.
[1] Stovner LJ, Hagen K, Linde M, Steiner TJ. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. Journal of Headache and Pain. 2022; 23: 34.
[2] Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018; 38: 1–211.
[3] GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet. 2016; 388: 1545–1602.
[4] Krause DN, Warfvinge K, Haanes KA, Edvinsson L. Hormonal influences in migraine—interactions of oestrogen, oxytocin and CGRP. Nature Reviews Neurology. 2021; 17: 621–633.
[5] Su M, Yu S. Chronic migraine: a process of dysmodulation and sensitization. Molecular Pain. 2018; 14: 1744806918767697.
[6] Charles A. The pathophysiology of migraine: implications for clinical management. The Lancet Neurology. 2018; 17: 174–182.
[7] Pérez-Pereda S, Toriello-Suárez M, Ocejo-Vinyals G, Guiral-Foz S, Castillo-Obeso J, Montes-Gómez S, et al. Serum CGRP, VIP, and PACAP usefulness in migraine: a case-control study in chronic migraine patients in real clinical practice. Molecular Biology Reports. 2020; 47: 7125–7138.
[8] Sun S, Fan Z, Liu X, Wang L, Ge Z. Microglia TREM1-mediated neuroinflammation contributes to central sensitization via the NF-κB pathway in a chronic migraine model. Journal of Headache and Pain. 2024; 25: 3.
[9] Ustianowska K, Ustianowski Ł, Machaj F, Gorący A, Rosik J, Szostak B, et al. The role of the human microbiome in the pathogenesis of pain. International Journal of Molecular Sciences. 2022; 23: 13267.
[10] Liu L, Wu Q, Chen Y, Ren H, Zhang Q, Yang H, et al. Gut microbiota in chronic pain: novel insights into mechanisms and promising therapeutic strategies. International Immunopharmacology. 2023; 115: 109685.
[11] Kataoka K. The intestinal microbiota and its role in human health and disease. The Journal of Medical Investigation. 2016; 63: 27–37.
[12] Williams NT. Probiotics. American Journal of Health-System Pharmacy. 2010; 67: 449–458.
[13] Xu Z, Jiang N, Xiao Y, Yuan K, Wang Z. The role of gut microbiota in liver regeneration. Frontiers in Immunology. 2022; 13: 1003376.
[14] Qiu P, Ishimoto T, Fu L, Zhang J, Zhang Z, Liu Y. The gut microbiota in inflammatory bowel disease. Frontiers in Cellular and Infection Microbiology. 2022; 12: 733992.
[15] Mangiola F, Ianiro G, Franceschi F, Fagiuoli S, Gasbarrini G, Gasbarrini A. Gut microbiota in autism and mood disorders. World Journal of Gastroenterology. 2016; 22: 361–368.
[16] Góralczyk-Bińkowska A, Szmajda-Krygier D, Kozłowska E. The microbiota-gut-brain axis in psychiatric disorders. International Journal of Molecular Sciences. 2022; 23: 11245.
[17] Quigley EMM. Microbiota-brain-gut axis and neurodegenerative diseases. Current Neurology and Neuroscience Reports. 2017; 17: 94.
[18] Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, Soleimanpour S. A comprehensive review on the role of the gut microbiome in human neurological disorders. Clinical Microbiology Reviews. 2022; 35: e0033820.
[19] González Olmo BM, Butler MJ, Barrientos RM. Evolution of the human diet and its impact on gut microbiota, immune responses, and brain health. Nutrients. 2021; 13: 196.
[20] Marano G, Mazza M, Lisci FM, Ciliberto M, Traversi G, Kotzalidis GD, et al. The microbiota-gut-brain axis: psychoneuroimmunological insights. Nutrients. 2023; 15: 1496.
[21] Agirman G, Yu KB, Hsiao EY. Signaling inflammation across the gut-brain axis. Science. 2021; 374: 1087–1092.
[22] Iannone LF, Preda A, Blottière HM, Clarke G, Albani D, Belcastro V, et al. Microbiota-gut brain axis involvement in neuropsychiatric disorders. Expert Review of Neurotherapeutics. 2019; 19: 1037–1050.
[23] Claudino Dos Santos JC, Lima MPP, Brito GAC, Viana GSB. Role of enteric glia and microbiota-gut-brain axis in parkinson disease pathogenesis. Ageing Research Reviews. 2023; 84: 101812.
[24] Kong G, Ellul S, Narayana VK, Kanojia K, Ha HTT, Li S, et al. An integrated metagenomics and metabolomics approach implicates the microbiota-gut-brain axis in the pathogenesis of Huntington’s disease. Neurobiology of Disease. 2021; 148: 105199.
[25] Mugo CW, Church E, Horniblow RD, Mollan SP, Botfield H, Hill LJ, et al. Unravelling the gut-brain connection: a systematic review of migraine and the gut microbiome. Journal of Headache and Pain. 2025; 26: 125.
[26] Gazerani P, Papetti L, Dalkara T, Cook CL, Webster C, Bai J. The brain, the eating plate, and the gut microbiome: partners in migraine pathogenesis. Nutrients. 2024; 16: 2222.
[27] Kiecka A, Szczepanik M. Migraine and the microbiota. Can probiotics be beneficial in its prevention?—A narrative review. Pharmacological Reports. 2024; 76: 251–262.
[28] Gazerani P. Diet and migraine: what is proven? Current Opinion in Neurology. 2023; 36: 615–621.
[29] Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. The BMJ. 2021; 372: n71.
[30] Alammary A. Blended learning models for introductory programming courses: a systematic review. PLOS ONE. 2019; 14: e0221765.
[31] Richardson WS, Wilson MC, Nishikawa J, Hayward RS. The well-built clinical question: a key to evidence-based decisions. ACP Journal Club. 1995; 123: A12–A13.
[32] Suurmond R, van Rhee H, Hak T. Introduction, comparison, and validation of meta-essentials: a free and simple tool for meta-analysis. Research Synthesis Methods. 2017; 8: 537–553.
[33] Walters KE, Martiny JBH. Alpha-, beta-, and gamma-diversity of bacteria varies across habitats. PLOS ONE. 2020; 15: e0233872.
[34] Bai J, Shen N, Liu Y. Associations between the gut microbiome and migraines in children aged 7–18 years: an analysis of the American gut project cohort. Pain Management Nursing. 2023; 24: 35–43.
[35] Liu J, Xi K, Zhang L, Han M, Wang Q, Liu X. Tryptophan metabolites and gut microbiota play an important role in pediatric migraine diagnosis. Journal of Headache and Pain. 2024; 25: 2.
[36] Chen J, Wang Q, Wang A, Lin Z. Structural and functional characterization of the gut microbiota in elderly women with migraine. Frontiers in Cellular and Infection Microbiology. 2020; 9: 470.
[37] Geisler C, Pankoke J, Schlicht K, Knappe C, Rohmann N, Hartmann K, et al. BMI, alcohol consumption and gut microbiome species richness are related to structural and functional neurological abnormalities. Nutrients. 2021; 13: 3743.
[38] Yong D, Lee H, Min HG, Kim K, Oh HS, Chu MK. Altered gut microbiota in individuals with episodic and chronic migraine. Scientific Reports. 2023; 13: 626.
[39] Kopchak OO, Hrytsenko OY, Pulyk OR. Peculiarities of the gut microbiota in patients with migraine comparing to healthy individuals. Wiadomosci Lekarskie. 2022; 75: 2218–2221.
[40] Liu J, Tang W, Hou L, Wang J, Wang R, Zhang Y, et al. Alteration of gut microbiota in migraine patients with irritable bowel syndrome in a Chinese Han population. Frontiers in Neurology. 2022; 13: 899056.
[41] Georgescu D, Iurciuc MS, Ionita I, Dragan S, Muntean M, Ancusa OE, et al. Migraine without aura and subclinical atherosclerosis in young females: is gut microbiota to blame? Medicina. 2019; 55: 786.
[42] Meng X, Li Q, Wang D, Li J, Cui Y, Sun Z, et al. Exploring the role of gut microbiota in migraine risk: a two-sample Mendelian randomization study. Scandinavian Journal of Gastroenterology. 2023; 59: 411–418.
[43] He Q, Wang W, Xiong Y, Tao C, Ma L, Ma J, et al. A causal effects of gut microbiota in the development of migraine. Journal of Headache and Pain. 2023; 24: 90.
[44] Lanza M, Filippone A, Casili G, Giuffrè L, Scuderi SA, Paterniti I, et al. Supplementation with SCFAs re-establishes microbiota composition and attenuates hyperalgesia and pain in a mouse model of NTG-induced migraine. International Journal of Molecular Sciences. 2022; 23: 4847.
[45] Tang Y, Liu S, Shu H, Yanagisawa L, Tao F. Gut microbiota dysbiosis enhances migraine-like pain via TNFα upregulation. Molecular Neurobiology. 2020; 57: 461–468.
[46] Miao S, Tang W, Li H, Li B, Yang C, Xie W, et al. Repeated inflammatory dural stimulation-induced cephalic allodynia causes alteration of gut microbial composition in rats. Journal of Headache and Pain. 2022; 23: 71.
[47] Ghavami A, Khorvash F, Heidari Z, Khalesi S, Askari G. Effect of synbiotic supplementation on migraine characteristics and inflammatory biomarkers in women with migraine: results of a randomized controlled trial. Pharmacological Research. 2021; 169: 105668.
[48] Martami F, Togha M, Seifishahpar M, Ghorbani Z, Ansari H, Karimi T, et al. The effects of a multispecies probiotic supplement on inflammatory markers and episodic and chronic migraine characteristics: a randomized double-blind controlled trial. Cephalalgia. 2019; 39: 841–853.
[49] Biagioli V, Mela F, Ferraro P, Villano G, Orsini A, Diana MC, et al. The interplay between gut microbiota, adipose tissue, and migraine: a narrative review. Nutrients. 2025; 17: 337.
Science Citation Index (SCI)
Science Citation Index Expanded (SCIE)
BIOSIS Previews
Scopus: CiteScore 3.1 (2024)
Cumulative Index to Nursing and Allied Health Literature (CINAHL)
Top