Many of the 38 million Americans who suffer from migraines have noticed an association between consuming nitrates and their severe headaches. Nitrates, found in foods like processed meats, green leafy vegetables, and in certain medicines, can be reduced to nitrites by bacteria found in the oral cavity. About 80% of cardiac patients who take nitrate-containing drugs for chest pain or congestive heart failure report severe headaches as a side effect. The researchers speculate that we may have a symbiotic relationship with our oral microbes, which aids our cardiovascular health, or that too many nitrate-reducing bacteria in the mouth may also lead to migraines.
These nitrites when circulating in the blood can then be converted to nitric oxide (NO) under certain conditions, which is a powerful vasodilator that can aid cardiovascular health by improving blood flow and reducing blood pressure.
"There is this idea out there that certain foods trigger migraines--chocolate, wine, and especially foods containing nitrates," says Antonio Gonzalez, a programmer analyst in the laboratory of Rob Knight at UC San Diego, and lead author on the study. "We thought that perhaps there was a connection between someone's microbiome and what they were eating."
Using publicly available data from the American Gut Project run out of the Knight lab, Gonzalez and his colleague Embriette Hyde sequenced bacteria found in 172 oral samples and 1,996 fecal samples from healthy participants. The participants had previously filled out surveys indicating whether they suffered from migraines.
The sequencing first told them which bacterial species were found in different abundances between migraineurs and non-migraineurs. In terms of bacterial community composition, the team did not find huge differences in either fecal or oral samples from migraineurs compared to non-migraneurs.
Next, they used a bioinformatic tool called PICRUSt to analyze which genes were likely to be present in the two different sets of samples, given the bacterial species present. In fecal samples, they found a slight, but statistically significant increase in the abundance of genes that encoding nitrate, nitrite and nitric oxide reductases in migraineurs. In oral samples, these genes were significantly more abundant in migraineurs.
"We know for a fact the nitrate-reducing bacteria are found in the oral cavity," says Hyde, who is the project manager for the American Gut Project in the Knight laboratory. "We definitely think this pathway is advantageous to cardiovascular health, but now we have a potential connection to migraines as well."
Gonzalez and Hyde say that the next steps will be to look at more defined groups of patients, separated into the handful of different types of migraines. Then, researchers can determine if their oral microbes really do express those nitrate-reducing genes, measure their levels of circulating NO and see how they correlate with migraine status.
Perhaps far into the future, Gonzalez speculates, "We will have a magical probiotic mouthwash for everyone that helps your cardiovascular health without giving you migraines." But for now, he says, "If you suspect that nitrates are causing you migraines, you should try to avoid them in your diet."