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
. 2025 Sep;12(5):e200437.
doi: 10.1212/NXI.0000000000200437. Epub 2025 Jun 30.

Oral and Gut Dysbiosis in Migraine: Oral Microbial Signatures as Biomarkers of Migraine

Soomi Cho  1 , Yeonjae Jung  2 , Hyun-Seok Oh  2 , Jungyon Yum  1 , Seungwon Song  1 , JaeWook Jeong  1 , Woo-Seok Ha  1 , Kyung Min Kim  1 , Won-Joo Kim  3 , Min Kyung Chu  1
Affiliations

Oral and Gut Dysbiosis in Migraine: Oral Microbial Signatures as Biomarkers of Migraine

Soomi Cho et al. Neurol Neuroimmunol Neuroinflamm. 2025 Sep.

Abstract

Background and objectives: Emerging evidence suggests that oral health conditions may exacerbate migraine, and saliva is a potential source of biomarkers for migraine. The 3-way interaction of the oral-gut-brain axis has been implicated in several neurologic disorders, but has rarely been studied in migraine. This study examined the oral and gut microbiomes simultaneously and identified several key oral microbes that may influence migraine.

Methods: In this cross-sectional case-control study, participants were divided into 3 groups: episodic migraine (n = 55), chronic migraine (n = 55), and healthy control (HC) (n = 55). Demographic and clinical characteristics; lifestyle factors; and biological samples including saliva, stool, and blood were collected. Composition, function, and community type of the oral and gut microbiomes were compared among the 3 groups.

Results: Oral dysbiosis was more pronounced than gut dysbiosis in the migraine groups, with 13 oral genera significantly enriched or depleted compared with HCs. The migraine groups showed increased abundance of Gemella, Streptococcus, Granulicatella, and Rothia and decreased abundance of Alloprevotella, Veillonella, Haemophilus, Selenomonas, Campylobacter, Cardiobacterium, Megasphaera, and Kingella after adjustment for demographic and lifestyle factors including diet. The enriched oral genera within the migraine groups were associated with carbohydrate metabolic pathways, whereas the depleted oral genera were associated with pathways related to nitrogen. A significant proportion of the oral microbial signatures of migraine included genera capable of reducing nitrate and/or nitrite. Some of these oral microbial signatures of migraine had a relative abundance that was positively or negatively associated with the number of headache days per 30 days and formed distinct microbial clusters in both the oral cavity and gut. Machine learning classifiers using the oral microbiome effectively classified migraine status, with an area under the receiver-operating characteristic curve of 0.83-0.88.

Discussion: Our findings suggest that oral dysbiosis may be involved in the development of migraine and highlight specific oral microbes as potential diagnostic biomarkers and therapeutic targets for migraine.

PubMed Disclaimer

Conflict of interest statement

Y. Jung and H.-S. Oh are employees of CJ Bioscience Inc. M.K. Chu was a site investigator for a multicenter trial sponsored by Biohaven Pharmaceuticals, Allergan Korea, and Ildong Pharmaceutical Company. M.K. Chu received lecture honoraria from Eli Lilly and Company, Handok-Teva, and Ildong Pharmaceutical Company over the past 24 months. M.K. Chu 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. Go to Neurology.org/NN for full disclosures.

Figures

Figure 1
Figure 1. Oral and Gut Microbiome Diversity in the CM, EM, and HC Groups
Alpha diversity (left) and number of taxa observed at the genus level (right) of (A) oral and (B) gut microbiomes. Beta diversity of PCoA based on Bray-Curtis dissimilarity at the genus level of (C) oral and (D) gut microbiomes. ****p < 0.0001; *p < 0.05. CM = chronic migraine; EM = episodic migraine; HC = healthy control; ns = not significant; PCoA = principal coordinate analysis.
Figure 2
Figure 2. Differential Abundance of the Oral Microbiome at the Genus Level Between (A) CM and HC, (B) EM and HC, and (C) Venn Diagram of Overlapping Altered Taxa
(C) Venn diagram of oral microbial signatures increased or decreased in the CM and/or EM groups compared with those in the HC group. Magenta represents taxa enriched in participants with migraine, and green represents taxa enriched in controls. AUC = area under the receiver-operating characteristic curve; CM = chronic migraine; EM = episodic migraine; HC = healthy control.
Figure 3
Figure 3. Differential Abundance of Functional Metabolic Pathway Profiles of the Oral Microbiome Between (A) CM and HC or (B) EM and HC Groups
In the volcano plot, the x-axis represents the fold change (FC) between 2 comparison groups, while the y-axis represents the p value. The features with an adjusted p < 0.05 are colored according to their pathway class, and the significant features with FC ≥ 0.1 are additionally labeled with text. (C) A heatmap of Spearman correlation results of percentage abundances of pathways and taxa to represent the association between taxonomic oral signatures and estimated functional KEGG metabolic pathway signatures. Spearman's rho values, are represented by heatmap colors, and p < 0.05 are highlighted with an asterisk. CM = chronic migraine; EM = episodic migraine; HC = healthy control; KEGG = Kyoto Encyclopedia of Genes and Genomes.
Figure 4
Figure 4. Ecological Structures of the (A) Oral and (B) Gut Microbiome at the Genus Level
Relative proportions of ecological structure types across groups for the (A, upper left) oral and (B, upper left) gut microbiomes. PCoA plot based on Bray-Curtis dissimilarity by ecological structures of the (A, lower left) oral and (B, lower left) gut microbiomes. LEfSe analysis comparing the genus profiles of the (A, right) oral and (B, right) gut microbiomes by ecological structure. LEfSe = linear discriminant analysis effect size; PCoA = principal coordinate analysis.
Figure 5
Figure 5. Machine Learning–Based Classification of Migraine—(A) Migraine, (B) CM, and (C) EM—Using Host-Derived Features, Oral Microbial Signatures, and Combinations of Host-Derived Features and Oral Microbial Signatures
CM = chronic migraine; EM = episodic migraine.
See this image and copyright information in PMC

References

    1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211-1259. doi: 10.1016/S0140-6736(17)32154-2 - DOI - PMC - PubMed
    1. Ashina M, Katsarava Z, Do TP, et al. Migraine: epidemiology and systems of care. Lancet. 2021;397:1485-1495. doi: 10.1016/s0140-6736(20)32160-7 - DOI - PubMed
    1. Silberstein SD. Migraine pathophysiology and its clinical implications. Cephalalgia. 2004;24:2-7. doi: 10.1111/j.1468-2982.2004.00892.x - DOI - PubMed
    1. Ashina M, Hansen JM, Do TP, Melo-Carrillo A, Burstein R, Moskowitz MA. Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol. 2019;18:795-804. doi: 10.1016/s1474-4422(19)30185-1 - DOI - PMC - PubMed
    1. Patacchioli FR, Monnazzi P, Simeoni S, et al. Salivary cortisol, dehydroepiandrosterone-sulphate (DHEA-S) and testosterone in women with chronic migraine. J Headache Pain. 2006;7:90-94. doi: 10.1007/s10194-006-0274-6 - DOI - PMC - PubMed