Acupuncture regulates gut microbiota and metabolites in a rat model of chronic migraine

Abstract

Objective: The aim of this study was to investigate the effects of acupuncture on a rat model of chronic migraine (CM) and explore the underlying mechanism of action from the perspective of the gut–brain axis. Methods: A total of 24 male Sprague-Dawley (SD) rats were randomly allocated into control, model and acupuncture groups (n = 8 each). The CM model was established by intraperitoneal injection of nitroglycerin (NTG). Acupuncture was administered at GV20 and bilateral PC6/LR3/ST36 for rats in the acupuncture group once a day for 9 days. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in plasma. A combination of 16S rDNA sequencing and liquid chromatography-mass spectrometry (LC-MS) metabolomics was adopted to investigate the role of the gut–brain axis in migraine chronification and the effect of acupuncture on CM. Results: Acupuncture treatment significantly attenuated hyperalgesia in CM model rats and regulated serum levels of brain–gut peptides, including 5-HT, CGRP and VIP. Furthermore, the gut microbial community structure and metabolic profile changed in CM rats and acupuncture impacted the changes. Notably, acupuncture modulated 10 gut microbial genera and 13 fecal metabolites. Conclusion: These findings suggest that the gut–brain axis may play an important role in the chronification of migraine, and the regulation of gut microbiota and metabolites may be one of the mechanisms underlying the analgesic effect of acupuncture in CM.