Abstract
Accumulating evidence suggests that natural medicines have notable curative effects on neurological conditions, such as migraine, that are mediated by regulating the gut microbial flora. A natural medicine pair used in traditional Chinese medicine, Gastrodia elata Blume and Uncaria rhynchophylla (Miq.) Miq. ex Havil. (GU), have shown excellent effect in treating migraine, yet the role of gut microbes in the therapeutic effect of GU in chronic migraine (CMG) is unknown. Here, we performed a 16S rRNA gene sequencing and metabolomics study of the effects of GU in a nitroglycerin (NTG)-induced rat model of CMG. Our results showed that the gut microbial community structure changed significantly and was similar to that of control rats after GU administration in CMG rats. Specifically, GU increased the relative abundance of Bacteroides and Coprococcus and reduced the abundance of Prevotella_1 and Escherichia-Shigella in CMG rats. The metabolomics profiles of the plasma and ileum contents of CMG rats obtained with an ultra-performance liquid chromatography-mass spectrometer (UPLC-MS) revealed similar biomarkers in both samples, and GU treatment reduced 3-indoxyl sulfate, glutamic acid, L-tyrosine, and L-arginine levels, and increased 5-HIAA, L-tryptophan, and linoleic acid levels in plasma. Correlation analysis showed that the affected bacteria were closely related to amino acid metabolism. Most importantly, GU treatment hardly affected biomarkers in feces samples after inhibiting the activity of gut microbes. Collectively, these findings indicate that structural changes in gut flora are closely related to host metabolism and that regulating the gut microbial community structure and function may be one of the important mechanisms underlying the therapeutic effects of GU in migraine.
Highlights
Migraine, a severe type of headache, is a common chronic neurovascular disorder with recurrent episodes that seriously affects the lives of patients [Headache Classification Committee of the International Headache Society (IHS), 2013]
Eighteen compounds were identified in the GU extract, of which four major active ingredients, gastrodin, parishin A, rhynchophylline, and isorhynchophylline, were identified using standards (Herbpurify Co., Ltd, Chengdu, China) and others were identified by examining their characteristic product ions
The main contribution of this study is that clarification of the pathogenesis of migraine and the therapeutic effect of GUW is provided by the combination of 16S rRNA sequencing with metabolomics based on ultra-performance liquid chromatography-mass spectrometer (UPLC-MS)
Summary
A severe type of headache, is a common chronic neurovascular disorder with recurrent episodes that seriously affects the lives of patients [Headache Classification Committee of the International Headache Society (IHS), 2013]. Several studies have shown that disturbances of intestinal flora may be associated with neurological disorders, including migraine headache (Foster et al, 2016; Tang et al, 2019). The dysbiosis of gut flora could affect the brain–gut axis, which would promote neurotransmitter disorders, and this appears to be true for migraine-associated neurotransmitters (Grover and Kashyap, 2014). In particular, natural products taken orally, reach the intestine and are readily metabolized by gut flora. They are decomposed into metabolites with polarity and lower molecular weight, having higher bioavailability. To study the mechanism of GU in treating migraine, we need to study the function of intestinal flora and metabolism in vivo. Omics synthesis was applied to study the treatment mechanism of GU on migraine (Lionetto et al, 2013; Gasparini et al, 2017)
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