Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2026 Jan 10;27(1):38.
doi: 10.1186/s10194-026-02268-4.

Altered serum short-chain fatty acid profiles in episodic and chronic migraine and their modulation by preventive treatment

Soomi Cho #  1 , Sang-Guk Lee #  2 , Hye Jeong Lee  3 , Jungyon Yum  4 , Woo-Seok Ha  1 , Kyung Min Kim  1 , Min Kyung Chu  5   6
Affiliations

Altered serum short-chain fatty acid profiles in episodic and chronic migraine and their modulation by preventive treatment

Soomi Cho et al. J Headache Pain. .

Abstract

Background: Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are gut-microbiota-derived metabolites implicated in gut–brain communication. This study aimed to characterize serum SCFA profiles in individuals with episodic migraine (EM) or chronic migraine (CM) compared with healthy controls (HC) and to examine associations between preventive treatment and these metabolites.

Methods: Adults with EM, CM, and age- and sex-matched HC were enrolled. Serum levels of acetate, propionate, and butyrate were quantified using liquid chromatography–tandem mass spectrometry. Group differences in SCFA levels were assessed using Quade’s nonparametric analysis of covariance, adjusting for age, sex, and body mass index. Multiple linear regression examined independent associations between preventive treatment and SCFA levels. Moderation analysis evaluated whether preventive treatment modified the association between SCFA levels and headache days per 30 days.

Results: Of the 476 participants (HC: n = 108; EM: n = 190; CM: n = 178), those with EM or CM without preventive treatment had lower serum butyrate levels than did HC (EM: p = 0.001; CM: p = 0.005), with no significant differences in acetate or propionate. Preventive treatment was independently associated with higher serum propionate levels (B = 0.805, 95% confidence interval [CI] = 0.395–1.215, p < 0.001) in those with CM but not in those with EM. Although preventive treatment did not significantly modify associations between SCFA levels and headache days per 30 days, higher butyrate levels were associated with a greater number of headache days in participants receiving preventive treatment (B = 7.967, 95% CI = 2.481–13.453, p = 0.005).

Conclusions: Serum SCFA profiles differed according to migraine status and preventive treatment use. Our findings highlight potential interactions among migraine, preventive therapy, and SCFA metabolism, warranting longitudinal studies to clarify directionality and underlying mechanisms.

Supplementary Information: The online version contains supplementary material available at 10.1186/s10194-026-02268-4.

Keywords: Gut-brain axis; Migraine disorders; Preventive treatment; Short-chain fatty acids.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of Severance Hospital, Yonsei University (IRB No. 2019-1403-005), and was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Prior to inclusion in the study, written informed consent was obtained from all the participants. Consent for publication: Not applicable. Competing interests: WSH serves as junior editor of The Journal of Headache and Pain. MKC serves as a board member of The Journal of Headache and Pain. MKC was a site investigator for a multicenter trial sponsored by Biohaven Pharmaceuticals, Allergan Korea, and Ildong Pharmaceutical Company. MKC received lecture honoraria from Eli Lilly and Company, Handok-Teva, and Ildong Pharmaceutical Company over the past 24 months. MKC received grants from Yonsei University College of Medicine (6-2021-0229) and the Korea Health Industry Development Institute (KHIDI) (HV22C0106) and a National Research Foundation of Korea (NRF) grant from the Korean government (MSIT) (2022R1A2C1091767). The other authors report no competing interests.

Figures

Fig. 1
Fig. 1
Serum (A) acetate, (B) propionate, and (C) butyrate levels in healthy controls, participants with episodic migraine and chronic migraine Boxplots represent the interquartile range with median values, and outliers are plotted as points. Between-group differences were tested using Quade’s nonparametric analysis of covariance, adjusted for age, sex, and body mass index. Significance levels are indicated as p < 0.001 (***), and ns (not significant).Abbreviations: CM = chronic migraine; EM = episodic migraine; HC = healthy control
Fig. 2
Fig. 2
Serum (A) acetate, (B) propionate, and (C) butyrate levels in healthy controls, participants with episodic migraine without preventive treatment and chronic migraine without preventive treatment. Boxplots represent the interquartile range with median values, and outliers are plotted as points. Between-group differences were tested using Quade’s nonparametric analysis of covariance, adjusted for age, sex, and body mass index. Significance levels are indicated as p < 0.01 (**), p < 0.001 (***), and ns (not significant). Abbreviations: CMw/oP = chronic migraine without preventive treatment; EMw/oP = episodic migraine without preventive treatment; HC = healthy control
Fig. 3
Fig. 3
Serum (A) acetate, (B) propionate, and (C) butyrate levels in healthy controls, participants with episodic migraine with preventive treatment and chronic migraine with preventive treatment. Boxplots represent the interquartile range with median values, and outliers are plotted as points. Between-group differences were tested using Quade’s nonparametric analysis of covariance, adjusted for age, sex, and body mass index. Significance levels are indicated as p < 0.017 (*), p < 0.001 (***), and ns (not significant). Abbreviations: CMwP = chronic migraine with preventive treatment; EMwP = episodic migraine with preventive treatment; HC = healthy control
Fig. 4
Fig. 4
Interaction between serum butyrate and preventive medication use on headache days per 30 days. Butyrate values were mean-centered for analysis and visualization. Predicted headache days per 30 days across centered butyrate levels are plotted separately according to preventive medication use. Shaded areas represent 95% confidence intervals. Analyses were adjusted for age, sex, and body mass index
See this image and copyright information in PMC

References

    1. Ashina M, Katsarava Z, Do TP et al (2021) Migraine: epidemiology and systems of care. Lancet 397(10283):1485–1495. 10.1016/s0140-6736(20)32160-7 - DOI - PubMed
    1. Stovner LJ, Nichols E, Steiner TJ et al (2018) Global, regional, and National burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol 17(11):954–976. 10.1016/S1474-4422(18)30322-3 - DOI - PMC - PubMed
    1. Steiner TJ, Stovner LJ, Jensen R, Uluduz D, Katsarava Z (2020) Migraine remains second among the world’s causes of disability, and first among young women: findings from GBD2019. J Headache Pain 21(1):137. 10.1186/s10194-020-01208-0 - DOI - PMC - PubMed
    1. Eigenbrodt AK, Ashina H, Khan S et al (2021) Diagnosis and management of migraine in ten steps. Nat Rev Neurol 17(8):501–514. 10.1038/s41582-021-00509-5 - DOI - PMC - PubMed
    1. Ashina M, Buse DC, Ashina H et al (2021) Migraine: integrated approaches to clinical management and emerging treatments. Lancet 397(10283):1505–1518. 10.1016/S0140-6736(20)32342-4 - DOI - PubMed

LinkOut - more resources