All Roads Lead to the Gut: The Importance of the Microbiota and Diet in Migraine

Abstract

Migraine, a prevalent neurological condition and the third most common disease globally, places a significant economic burden on society. Despite extensive research efforts, the precise underlying mechanism of the disease remains incompletely comprehended. Nevertheless, it is established that the activation and sensitization of the trigeminal system are crucial during migraine attacks, and specific substances have been recognized for their distinct involvement in the pathomechanism of migraine. Recently, an expanding body of data indicates that migraine attacks can be prevented and treated through dietary means. It is important to highlight that the various diets available pose risks for patients without professional guidance. This comprehensive overview explores the connection between migraine, the gut microbiome, and gastrointestinal disorders. It provides insight into migraine-triggering foods, and discusses potential diets to help reduce the frequency and severity of migraine attacks. Additionally, it delves into the benefits of using pre- and probiotics as adjunctive therapy in migraine treatment.

Keywords: dietary triggers; diets; gut microbiome; gut-bran axis; headache; migraine; nutrition; prebiotics; probiotics.

Figure 1

Migraine’s phases and the factors assumed to be involved in its pathomechanism. (A) The four phases of migraine: the premonitory (prodrome) phase, a possible aura, the headache, and recovery (post-drome). (B) Vascular dysfunction, CSD, activation of the trigeminovascular pathway, and inflammatory and oxidative conditions may play a fundamental role in the development of mi-graine pain. Moreover, nutrition and the composition and function of the gut microbiome influence the development of migraine attacks. The trigeminal ganglion (TG) originates pseudo-unipolar trigeminal primary sensory neurons that establish connections with both intra- and extracranial structures, including blood vessels, as well as the spinal cord’s trigeminocervical complex (TCC) (black line). Second-order neurons arising from the TCC ascend via the trigeminothalamic tract, where they form synapses with third-order thalamocortical neurons. There are also direct and indirect ascending projections to the locus coeruleus (LC), periaqueductal gray (PAG), and hypothalamus. Subsequently, these third-order thalamocortical neurons synapse within an extensive network of cortical regions (red line). There is also activation of the parasympathetic reflex through the outflow from the superior salivatory nucleus (SSN) via the facial nerve, predominantly involving the sphenopalatine ganglion (SPG), which acts to dilate blood vessels and activate trigeminal nerve endings (green line). CTX, cortex; NO, nitric oxide; CSD, cortical spreading depression; Th, thalamus; hTh, hypothalamus; LP, lateral posterior nucleus; VPM, ventral posteromedial nucleus; VPL, ventral posterolateral nucleus; PAG, periaqueductal grey matter; LC, locus coeruleus; TCC, trigeminocervical complex; SSN, superior salivatory nucleus; SpV, spinal trigeminal nucleus caudalis; TG, trigeminal ganglion; SPG, sphenopalatine ganglion; V1, ophthalmic nerve; V2, maxillary nerve; V3, mandibular nerve.

Figure 2

Bidirectional connection between the brain and the gut microbiome in both a healthy and abnormal state. CNS, central nervous system; ANS, autonomic nervous system; HPA, hypothalamic–pituitary–adrenal; SCFAs, short-chain fatty acids; GI, gastrointestinal.

Figure 3

The relationship between migraine, gastrointestinal disorders and microbiota. Changes in sympathetic and parasympathetic activity and the gut microbiota profile—mediated by different cytokines, hormones and neurotransmitters—contribute to the development of migraine and GI diseases [46]. CGRP, calcitonin gene-related peptide; CRH, corticotrophin-releasing hormone; ACh, acetylcholine; 5-HT, serotonin; TNC, trigeminal nucleus caudalis; DMV, dorsal motor nucleus of the vagus; GI; gastrointestinal.

Figure 4

Potential dietary factors of migraine. Scientific evidence suggests that certain foods can trigger migraine attacks. Common migraine-triggering foods include chocolate, coffee, and red wine.

Figure 5

The beneficial effect of pre- and probiotics. Recently, pre-and probiotics have become the focus of migraine treatment, as the gut microbiota can influence the function of the CNS through various mechanisms. Taking pre- and probiotics can help restore and maintain a healthy gut microbiome, and can thus affect the frequency and severity of migraines. SCFAs, short-chain fatty acids, BBB, blood–brain barrier.