Summary: Researchers found that people who experience migraines have significantly higher levels of oral microbes capable of modifying nitrates than those who do not suffer from migraine headaches.
Source: UCSD.
Researchers at the University of California San Diego School of Medicine report that the mouths of people who suffer from migraines contain significantly more nitrate-modifying microbes than those of people who do not get migraines. The study was published October 18 in mSystems.
“There is a common belief that certain foods can trigger migraines — chocolate, wine and particularly foods or medicines containing nitrates,” said Antonio Gonzalez, the study’s first author and a programmer analyst in the laboratory of Rob Knight, PhD, professor and director of the Center for Microbiome Innovation at UC San Diego, who is senior author on the paper. “We explored whether diet, the microbiome and migraine experiences might be connected.”
Many of the roughly 38 million Americans who suffer from migraines report that nitrate-containing foods or drugs provoke their headaches. Nitrates, which occur in processed meats, leafy green vegetables and some medications, can be reduced by oral bacteria into nitrites. Once in the bloodstream, nitrites can be converted into nitric oxide under certain conditions. Nitric oxide has beneficial cardiovascular effects by improving blood flow and lowering blood pressure, yet nitric oxide and nitrate-based drugs are also well-known to cause headaches in some patients — for example, many cardiac patients who take nitrate medications report severe headaches as a side effect.
The researchers used publicly available data from the American Gut Project, a crowdfunded citizen science initiative managed by the Knight lab, to investigate links between migraines and the microbiome. Gonzalez and co-author Embriette Hyde, PhD, analyzed bacterial DNA from 172 oral samples and 1,996 fecal samples collected from healthy volunteers who had completed surveys indicating whether they experienced migraines.
Sequencing revealed differences in the relative abundances of certain bacterial species between individuals who reported migraines (migraineurs) and those who did not. While overall community composition in fecal and oral samples did not show drastic shifts between the two groups, further analysis focusing on functional potential revealed a clearer pattern.
The team applied a bioinformatics tool called PICRUSt to predict which genes were likely present based on the bacterial species detected. In fecal samples they observed a modest but statistically significant increase in genes associated with nitrate, nitrite and nitric oxide metabolism among migraineurs. In oral samples this pattern was stronger: genes encoding nitrate-, nitrite- and nitric oxide-related enzymes were significantly more abundant in people who reported migraines.
“We already know that nitrate-reducing bacteria are common inhabitants of the oral cavity,” said Hyde, project manager for the American Gut Project and assistant project scientist in the Knight lab. “This nitrate-to-nitrite-to-nitric-oxide pathway can be beneficial for cardiovascular health, but our findings suggest a possible link to migraines. At this stage, however, we cannot say whether these microbes cause migraines, result from them, or are associated indirectly.”
Gonzalez and Hyde outlined next steps that include studying more clearly defined patient groups and different migraine subtypes. Future research will aim to directly measure whether oral microbes express the predicted nitrate-reducing genes, quantify circulating nitric oxide levels in individuals, and determine how these measures correlate with migraine occurrence and severity.
Co-authors of the study include Naseer Sangwan and Jack A. Gilbert (University of Chicago) and Erik Viirre (UC San Diego).
Funding: The research was supported by crowdfunding contributions from participants in the American Gut Project.
Source: Heather Buschman – UCSD
Image Source: NeuroscienceNews.com image adapted from a UCSD press release.
Original Research: Full open access research titled “Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort” by Antonio Gonzalez, Embriette Hyde, Naseer Sangwan, Jack A. Gilbert, Erik Viirre, and Rob Knight. Published online October 18, 2016. doi:10.1128/mSystems.00105-16
Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort
Nitrate-containing foods and medications are established headache triggers, and nitric oxide is implicated in migraine biology. Facultative anaerobic bacteria in the oral cavity can convert dietary and salivary nitrate to nitrite and then to nitric oxide via the salivary nitrate–nitrite–nitric oxide pathway. Using high-throughput sequencing, the authors detected significantly higher predicted abundances of genes encoding nitrate, nitrite and nitric oxide reductases in oral samples from individuals who reported migraines compared with non-migraineurs, with a smaller but significant difference observed in fecal samples.
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