Repeated inflammatory dural stimulation-induced cephalic allodynia causes alteration of gut microbial composition in rats

Abstract

Background Gut microbial dysbiosis and gut-brain axis dysfunction have been implicated in the pathophysiology of migraine. However, it is unclear whether migraine-related cephalic allodynia could induce the alteration of gut microbial composition. Methods A classic migraine rat model was established by repeated dural infusions of inflammatory soup (IS). Periorbital mechanical threshold and nociception-related behaviors were used to evaluate IS-induced cephalic allodynia and the preventive effect of topiramate. The alterations in gut microbial composition and potential metabolic pathways were investigated based on the results of 16 S rRNA gene sequencing. Microbiota-related short-chain fatty acids and tryptophan metabolites were detected and quantified by mass spectrometry analysis. Results Repeated dural IS infusions induced cephalic allodynia (decreased mechanical threshold), migraine-like behaviors (increased immobility time and reduced moving distance), and microbial composition alteration, which were ameliorated by the treatment of topiramate. Decreased Lactobacillus was the most prominent biomarker genus in the IS-induced alteration of microbial composition. Additionally, IS infusions also enhanced metabolic pathways of the gut microbiota in butanoate, propanoate, and tryptophan, while the increased tryptophan-related metabolites indole-3-acetamide and tryptophol in feces could be the indicators. Conclusions Inflammatory dural stimulation-induced cephalic allodynia causes the alterations of gut microbiota profile and microbial metabolic pathways.

Sodium Propionate Treatment Improves Facial Pain and Changes of Intestinal Flora and its Metabolites Induced by Stimulation of Dura Inflammation Soup in Rats

“…The results showed that compared with the untreated mice, the head and face hyperalgesia of the mice in the SCFAs treatment group was reversed, the mast cell infiltration and inflammatory reaction in the intestine were significantly reduced, and the intestinal wall permeability was improved [7,18] . A recent research result of our research group also shows that in the IS-induced chronic migraine rat model, intestinal microbiota and tryptophan metabolism pathway will also be affected, and the disorder of intestinal microbiota and metabolism has also been corrected to some extent after the use of drugs to treat migraine [19] . At the same time, intestinal microorganisms can also enhance the stimulation of ECCs by improving the utilization of tryptophan [10] .…”

To analyze the relationship between gut microbiota, metabolites and migraine: a two-sample Mendelian randomization study

“…Some observational studies have reported a relationship between gut microbiota and migraine ( Chen et al, 2019 ; Georgescu et al, 2019 ; Geisler et al, 2021 ; Kopchak et al, 2022 ; Kopchak and Hrytsenko, 2022 ; Liu et al, 2022 ; Miao et al, 2022 ; Bai et al, 2023 ; Yong et al, 2023 ). In the present study, the genus LachnospiraceaeUCG001 , which had not previously been identified, was discovered to be a risk factor for migraine for the first time.…”

A causal effects of gut microbiota in the development of migraine

“…Headache may also lead to the occurrence of dysbiosis. Miao and his colleagues have reported that headache due to meningitis could lead to dysbiosis in gut, and they think that inflammatory dural stimulation-induced cephalic headahce causes the alterations of gut microbiota profile and microbial metabolic pathways [ 34 ]. However, these studies cannot provide the causal association between dysbiosis of gut microbiota and migraine.…”