The microbiome is a hot topic in both clinical and pre-clinical research, with new evidence suggesting a link between the microbes living in our body and the ghastly throb in our heads. The ability of our microbiome to influence migraines is an area of active research, one which is contributing to the understanding of this complex neurological disorder. Studies have shown that dysbiosis of our microbiome may be implicated in migraine (1), a hypothesis which, if found true, raises the question; can probiotics – living microorganisms that can help to resolve dysbiosis – be used to treat migraine?

What are probiotics?

Probiotics are the type of live bacteria and yeasts we want residing in our body. These microorganisms can be found in the form of supplements and in fermented foods such as yoghurt, sauerkraut and kefir. Whilst it’s not fully understood how they work, it’s believed probiotics can help those who require them by replacing “good” bacteria when they’re lost, such as is the case when we take antibiotics, as well as helping to restore balance when dysbiosis occurs. Each strain of probiotic has its own unique properties and thus contributes different health benefits; something to be mindful of when selecting a probiotic.

Research Supporting Probiotic Treatment for Migraine

Determining whether our microbiome can be changed by probiotics with a knock-on effect on health is a major area of research with massive implications for migraineurs.

A recent study conducted by Martami and colleagues (2) showed that an oral probiotic was capable of improving various aspects of migraine headaches. In the double-blind, randomised placebo-controlled trial, 40 episodic and 39 chronic migraine patients received two capsules of a 14-strain probiotic mixture or placebo over 10 weeks. The results showed the mean frequency of attacks notably decreased in the probiotic groups compared to the placebo; 40% in the episodic group and 45% in the chronic group. Migraine intensity was also notably reduced in the probiotic groups compared to placebo; 29% reduction in the episodic group and 31% in the chronic group. In both groups, the use of abortive medication was also greatly reduced as was attack duration in the chronic probiotic group.

Another study showing a possible link between probiotic usage and migraine improvement looked at migraine development from a naturopathic point of view: that migraine is caused by an underlying dysfunction involving assimilation or elimination mechanisms. Their theory for probiotic use in migraine prevention is that probiotics should improve assimilation in most patients due to the probiotic’s ability to assist in the digestion and absorption of nutrients, allowing the body to repair itself. In this open-label trial, 40 migraineurs, over a 12-week period were given supplementation containing probiotics, minerals, vitamins, and herbs. Results showed a notable improvement in quality of life in approximately 80% of the subjects and pain relief in more than half of the migraineurs (3). Whether or not migraine improvement was due to probiotics themselves is unknown as they weren’t tested in isolation, but if the researcher’s hypothesis about assimilation and elimination mechanisms is correct, probiotics may be part of the solution. 

In yet another study, de Roos and colleagues assessed the efficacy of probiotic treatment in migraine (4) through the lens of gut permeability and inflammation, a link which has been well documented in research. They contend that probiotics may decrease intestinal permeability as well as inflammation and therefore reduce intensity and/or frequency of migraine headaches. 29 migraine patients took 2 grams per day of a probiotic food supplement during the 12 weeks. Results showed that the number of migraine days per month decreased notably and their scores on the Migraine Disability Assessment Scale (MIDAS) improved.

Interestingly, a very recent study (11) conducted by a team of Standford University researchers investigating the relationship between the microbiome, diet, and inflammation found that a diet rich in fermented foods (probiotics) can lead to an increase in gut microbial diversity and a decrease in molecular signs of inflammation; a compelling result when one considers the possible link between migraines and inflammation.  

Multi-strain probiotics tend to be used in studies looking at the link between microbiome and migraine. However, clinical research has shown that two strains of the same species may have very different effects on the host (5). Knowing exactly which microorganisms are more – or less – effective at improving migraine symptoms (i.e., understanding the strain-specific functions of the chosen probiotic) would be required to better understand the likely mechanism of action.

While probiotics could be an effective and beneficial supplement to improve migraine, mechanisms are not well understood. Currently, there is limited evidence from clinical studies of the positive effects of probiotics on migraine, thus further research in the form of large-scale randomized, placebo-controlled clinical trials (the gold standard) are required to confirm the observations of the above studies.

Ways In Which Probiotics May Reduce Migraine

While the exact mechanisms by which migraines occur is yet to be determined, there are various lines of evidence that point to the role of bacteria in migraine development:

Serotonin and probiotics

When a person suffers a migraine, their serotonin levels are lower than normal. What exactly triggers this serotonin dip is currently unknown. One of the things we do know is that microbes in the gut can directly alter neurotransmitter levels (6), which may enable them to communicate with neurons and influence brain activity. Multiple probiotic strains produce serotonin which could be involved in the beneficial effects seen in studies looking at the link between probiotics and migraine.

Gut permeability and probiotics

Stress is a common migraine trigger. This biological response to a perceived threat involves the release of cortisol, a hormone known to increase the permeability of the gut lining. How this impacts migraines is that when the gut lining is perturbed, a pro-inflammatory compound called lipopolysaccharide is able to enter the bloodstream and in turn sensitises pain receptors in trigeminal sensory neurons (those involved in migraine headaches). (7). Research has shown that probiotics can resolve stress-induced gut permeability in rodents (10) and reduce cortisol levels in humans (5).

GI Conditions and Probiotics

Patients who present with migraine headaches suffer from GI conditions more frequently than healthy controls and vice versa. Although the exact processes that link the different GI conditions with migraine remain unclear, the complex interplay between the brain and the gut, as well as increased intestinal permeability and inflammatory responses, may explain their associations (6). Gut microbes have been implicated in the pathophysiology of a relatively large number of GI disorders (9), some of the mechanisms of which include intestinal permeability, hormones, immune molecules and bacteria metabolites. An improvement in gut microbiota and reduction of inflammation can help strengthen gut and brain function, thus it can be inferred that probiotics may have a beneficial effect on migraineurs suffering from GI conditions.

Inflammation and probiotics

During an inflammatory response triggered by leakage of substances from our gut, our immune cells produce chemicals called cytokines which help to keep our immune system on high alert. Studies show that cytokines have been implicated in migraine pain and are increased during migraine attacks. Probiotic supplementation may have a positive effect on migraines by lowering pro-inflammatory cytokine levels (1)

Conclusion

Thanks to encouraging research findings, the role live bacteria and the gut may play in the management of migraine has piqued the interest of leading experts in the field. The use of probiotics to improve gut health and thus migraine is an intriguing proposition, one that should bring hope to the millions of migraine sufferers around the world. 

Brigid xx

References

(1)Arzani, M., Jahromi, S.R., Ghorbani, Z. et al. Gut-brain Axis and migraine headache: a comprehensive review. J Headache Pain 21, 15 (2020). https://doi.org/10.1186/s10194-020-1078-9

(2) Martami F, Togha M, Seifishahpar M, Ghorbani Z, Ansari H, Karimi T, Jahromi SR. The effects of a multispecies probiotic supplement on inflammatory markers and episodic and chronic migraine characteristics: A randomized double-blind controlled trial. Cephalalgia. 2019 Jun;39(7):841-853. doi: 10.1177/0333102418820102. Epub 2019 Jan 8. PMID: 30621517.

(3) James Sensenig N, Jeffrey Marrongelle D, CCN MJS (2001) T. Treatment of migraine with targeted nutrition focused on improved assimilation and elimination. Altern Med Rev 6(5):488–494

(4) de Roos NM, Giezenaar CG, Rovers JM, Witteman BJ, Smits MG, van Hemert S. The effects of the multispecies probiotic mixture Ecologic®Barrier on migraine: results of an open-label pilot study. Benef Microbes. 2015;6(5):641-6. doi: 10.3920/BM2015.0003. Epub 2015 Apr 22. PMID: 25869282.

(5) Douillard F.P., Ribbera A., Kant R., Pietilä T.E., Järvinen H.M., Messing M., Randazzo C.L., Paulin L., Laine P., Ritari J., et al. Comparative Genomic and Functional Analysis of 100 Lactobacillus Rhamnosus Strains and Their Comparison with Strain GG. PLoS Genet. 2013;9:e1003683. doi: 10.1371/journal.pgen.1003683

(6) Dai, Yu-Jie. “Potential Beneficial Effects of Probiotics on Human Migraine Headache: A Literature Review.” Pain Physician, vol. 20, no. 2150-1149, 2017, pp. 251-255, https://www.painphysicianjournal.com/current/pdf?article=NDExNA%3D%3D&journal=102.

(7) Diogenes A., Ferraz C.C.R., Akopian A.N., Henry M.A., Hargreaves K.M. LPS Sensitizes TRPV1 via Activation of TLR4 in Trigeminal Sensory Neurons. J. Dent. Res. 2011;90:759–764. doi: 10.1177/0022034511400225.

(8) Kato-Kataoka A., Nishida K., Takada M., Kawai M., Kikuchi-Hayakawa H., Suda K., Ishikawa H., Gondo Y., Shimizu K., Matsuki T., et al. Fermented Milk Containing Lactobacillus Casei Strain Shirota Preserves the Diversity of the Gut Microbiota and Relieves Abdominal Dysfunction in Healthy Medical Students Exposed to Academic Stress. Appl. Environ. Microbiol. 2016;82:3649–3658. doi: 10.1128/AEM.04134-15.

(9) Doulberis, Michael et al. “Is there an Association between Migraine and Gastrointestinal Disorders?.” Journal of clinical neurology (Seoul, Korea) vol. 13,3 (2017): 215-226. doi:10.3988/jcn.2017.13.3.215

(10) Sarkar, Amar et al. “Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals.” Trends in neurosciences vol. 39,11 (2016): 763-781. doi:10.1016/j.tins.2016.09.002

(11) Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, Topf M, Gonzalez CG, Van Treuren W, Han S, Robinson JL, Elias JE, Sonnenburg ED, Gardner CD, Sonnenburg JL. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021 Jul 6:S0092-8674(21)00754-6. doi: 10.1016/j.cell.2021.06.019. Epub ahead of print. PMID: 34256014.