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Migraine Sufferers Have More Microbes In Their Mouths And Guts

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Researchers at the University of California San Diego School of Medicine (UC San Diego) have found an association between migraines and microbes that reduce nitrates.

Analyzing data from the American Gut Project, they found that migraine sufferers harbored significantly more microbes in their mouths and guts with the ability to modify nitrates compared to people who do not get migraine headaches. Their report, which is published this week in mSystems®, an open-access journal of the American Society for Microbiology, will spur more research to find out which oral microorganisms are related to migraines and how they affect health.

“There is this idea out there that certain foods trigger migraines–chocolate, wine, and especially foods containing nitrates,” said 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.”

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. 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.

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,” said 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.”

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. But for certain people, this research suggests, too many nitrate-reducing bacteria in the mouth may also lead to migraines.

Gonzalez and Hyde said 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 said, “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.”


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