mSystems. 2016 Oct 18;1(5). pii: e00105-16.

Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort.

Gonzalez A¹, Hyde E¹, Sangwan N², Gilbert JA², Viirre E³, Knight R⁴.

Author information

¹Department of Pediatrics, University of California San Diego, San Diego, California, USA.
²Department of Surgery, University of Chicago, Chicago, Illinois, USA.
³Department of Neurosciences, University of California San Diego, San Diego, California, USA.
⁴Department of Pediatrics, University of California San Diego, San Diego, California, USA; Department of Computer Science and Engineering, University of California San Diego, San Diego, California, USA.

Abstract

Nitrates, such as cardiac therapeutics and food additives, are common headache triggers, with nitric oxide playing an important role. Facultative anaerobic bacteria in the oral cavity may contribute migraine-triggering levels of nitric oxide through the salivary nitrate-nitrite-nitric oxide pathway. Using high-throughput sequencing technologies, we detected observable and significantly higher abundances of nitrate, nitrite, and nitric oxide reductase genes in migraineurs versus nonmigraineurs in samples collected from the oral cavity and a slight but significant difference in fecal samples. IMPORTANCE Recent work has demonstrated a potentially symbiotic relationship between oral commensal bacteria and humans through the salivary nitrate-nitrite-nitric oxide pathway (C. Duncan et al., Nat Med 1:546-551, 1995, http://dx.doi.org/10.1038/nm0695-546). Oral nitrate-reducing bacteria contribute physiologically relevant levels of nitrite and nitric oxide to the human host that may have positive downstream effects on cardiovascular health (V. Kapil et al., Free Radic Biol Med 55:93-100, 2013, http://dx.doi.org/10.1016/j.freeradbiomed.2012.11.013). In the work presented here, we used 16S rRNA Illumina sequencing to determine whether a connection exists between oral nitrate-reducing bacteria, nitrates for cardiovascular disease, and migraines, which are a common side effect of nitrate medications (U. Thadani and T. Rodgers, Expert Opin Drug Saf 5:667-674, 2006, http://dx.doi.org/10.1517/14740338.5.5.667).