It has been reported that nitrate-containing compounds found in certain foods—typically, processed meats, leafy vegetables, chocolate and some wines—as well as food preservatives and nitrate-containing drugs may trigger migraines as a side effect, but the possible mechanistic connection between nitrates, gut microbiome and the likelihood of experiencing migraines is unknown.

A recent study, led by Rob Knight from the Department of Paediatrics at the University of California San Diego in California (USA), has found that migraine sufferers have higher levels of oral bacteria involved in processing nitrates, which could make them more sensitive to certain foods that may act as migraine triggers.

The researchers used 16S ribosomal ribonucleic acid (rRNA) high-throughput sequencing technologies to determine whether a connection exists between nitrate-reducing bacteria in oral and faecal samples and migraines. The presence and abundance of nitrate, nitrite, and nitric oxide reductase genes were determined in predicted metagenomes from 172 oral samples and 1,996 faecal samples from healthy participants in the American Gut Project cohort and correlated with self-reported migraine status.

Migraine sufferers had higher abundances of nitrate, nitrite, and nitric oxide (NO) reductase genes – all of them involved in nitrogen metabolism – in the predicted metagenomes in both oral and faecal sample (these genes showed a greater increase in oral samples than in faecal samples). These results suggest that bacteria in the mouth may therefore contribute to efficient breakdown of nitrate contained in foods and food preservatives, which are finally converted into nitric oxide in the blood stream, causing vessels in the brain and scalp to dilate.

Besides this, the study demonstrated that the genera Streptococcus and Pseudomonas were increased in the oral microbiomes of migraineurs when compared to nonmigraineurs; both of these have the potential to reduce nitrate. Rothia mucilaginosa and Haemophilus parainfluenzae also showed differential abundance patterns in the oral microbiome of migraineurs and nonmigraineurs and these bacteria have been previously reported (here and here) as some of the main nitrate reducers in the human oral cavity.

These results show for the first time a potential relationship between nitrate-, nitrite-, and nitric oxide-reducing bacteria and migraines, by reporting their higher abundances in the oral cavities of people with migraines than in the oral cavities of nonmigraineurs. Despite being only a correlational study, this work offers a potential explanation for why some people are more vulnerable than others to migraines and why some foods appear to act as triggers for migraines.



Gonzalez A, Hyde E, Sangwan N, Gilbert JA, Viirre E, Knight R. Migraines are correlated with higher levels of nitrate-, nitrite-, and nitric oxide-reducing oral microbes in the American Gut Project Cohort. mSystems. 2016; 1(5). doi: 10.1128/mSystems.00105-16.