The gut microbiome modulates nitroglycerin-induced migraine-related hyperalgesia in mice.

BACKGROUND: Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia. METHODS: Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control. RESULTS: In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-α concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-α in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control. CONCLUSION: Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine.

Alteration of gut microbiota in migraine patients with irritable bowel syndrome in a Chinese Han population.

Objective: Migraine is frequently reported in patients with irritable bowel syndrome (IBS), and emerging evidence suggests that gut microbiota plays a role in migraine and IBS. However, alterations in the gut microbiome in migraine patients with IBS remain unknown. This study aimed to explore the compositions of gut microbiota in migraine patients with IBS in a Chinese Han population. Methods: Sixteen migraine patients with IBS and thirteen age- and gender-matched IBS patients with similar dietary and lifestyle habits were enrolled in this pilot study. Demographic data, clinical data, eating habits, lifestyle habits, comorbidities, and medications were recorded using a unified case registration form. Questionnaires for the Migraine Disability Assessment (MIDAS), Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) were completed. Fecal samples were collected, and microbial DNA was extracted. Gut microbiota 16S ribosomal RNA (16S rRNA) gene sequencing targeting the V4 region was performed using the Illumina HiSeq 2500 high-throughput sequencing platform. The relationships between gut microbiota and clinical characteristics of migraine were analyzed. Results: The structure of gut microbiota differed between migraine patients with IBS and patients with IBS, while the richness and diversity of gut microbiota in migraine patients with IBS showed no significant difference from that of patients with IBS. We found a higher relative abundance of the genus Parabacteroides and a lower relative abundance of the genera Paraprevotella, Lachnospiraceae_UCG-010, Lactococcus, Collinsella, and Comamonas in migraine patients with IBS than in patients with IBS. According to random forest predictive models, the phylum Bacteroidota shows the most important role in migraine patients with IBS. Furthermore, no statistical correlation was found between significantly different taxa at the genus level and migraine clinical data. Conclusion: This study identified that altered gut microbiota occurred in Chinese Han migraine patients with IBS, but no correlation was found between gut microbiota and the clinical characteristics of migraine. Further study is needed to better understand the role of gut microbiota in the pathogenesis of migraine in IBS.