Are Migraines Linked to Mouth Bacteria?

 

Nitrates, including cardiac medications and food additives, are common headache triggers, mediated by nitric oxide, a potent vasodilator. Anaerobic bacteria in the mouth generate physiologically relevant levels of nitric oxide via the salivary nitrate-nitrite-nitric oxide pathway. Although these may have beneficial effects on cardiovascular health, they may also potentially trigger migraine.
The goal of this study by Viirre and colleagues was to compare nitrate, nitrite, and nitric oxide reductase genes in oral and stool samples from migraineurs vs nonmigraineurs, using high-throughput sequencing technologies.

Study Synopsis and Perspective

Researchers may have uncovered a mechanism behind nitrate-based triggers in migraine. They found that compared with people who do not experience migraines, those who do have significantly more nitrate, nitrite, and nitric oxide reductase genes in oral and fecal samples.
For this study, the investigators examined these genes in stool and oral samples from the American Gut Project, a global crowd-funded citizen science effort.
"The magic of this microbiome project is that they have technologies that not only can identify what species there are, but also the quantity of them," said study author and migraine specialist, Erik Viirre, MD, PhD, professor of neurosciences, University of California at San Diego.
"That's the key; everybody has millions of bacteria with hundreds of species in their body; it's the relative quantity of these bacteria that's important."
Their study was published online October 18 in mSystems, published by the American Society for Microbiology.
Nitrates are composed of 1 nitrogen atom and 3 oxygen atoms. When bacteria in the mouth break down nitrates, one of the oxygen atoms is removed, resulting in nitrites. When in the bloodstream, nitrites can be converted into nitric oxide.
The link between nitrates and headaches is not new. For example, it is known that consuming foods containing nitrates, such as wine, chocolate, and processed meats, triggers a headache in some people. As well, cardiac medications containing nitrates (eg, nitroglycerine) may cause severe headaches.
Immediate or Delayed
Nitrate-induced headaches typically manifest as relatively mild "immediate" headaches developing within 1 hour of medication ingestion or more severe "delayed" headaches occurring 3 to 6 hours after nitrate intake.
The literature suggests differing mechanisms behind these 2 types of headaches. Immediate headaches appear to be connected to nitric oxide-mediated vasodilation, whereas delayed headaches, similar to migraines triggered by foods, stress, or other factors, appear to be activated by release of calcitonin-gene-related peptide, glutamate, cyclic guanosine monophosphate, or S-nitrosylation-mediated changes in ion channel function.
For this analysis, the researchers sequenced bacteria found in 172 oral samples and 1996 fecal samples from donors who self-reported migraine status. Samples came from adults 20 to 69 years old with a body mass index of 18.5 to 30 kg/m², and no self-reported history of inflammatory bowel disease, diabetes, or antibiotic use in the past year.
The authors found differences in samples from people with migraines vs those without.
There were small but significant (P ≤.001) increases in nitrate, nitrite, and nitric oxide reductase genes in stool samples collected from migraineurs.
In oral samples, nitrate, nitrite, and nitric oxide reductase genes were all significantly more abundant in migraineurs (P ≤.001).
The researchers also used dominant oral operational taxonomic units (OTUs) to identify and quantify the various bacteria. The OTUs that significantly differed between migraineurs and nonmigraineurs belonged to the genera Streptococcus and Pseudomonas, both of which have species with the potential to reduce nitrate.
Reduced Process
The study showed that the percentages of sub-OTUs for both Streptococcus and Pseudomonas were smaller in migraineurs than in nonmigraineurs. If these bacteria process nitrates, the findings would suggest that this process is reduced in people with migraine, resulting in more nitrates in their body, they say.
Dr Viirre stressed that they have found only a correlation and cannot "make the leap" to say that these bacteria are the actual cause of headaches.
"Many other factors are associated with migraine, including genetic factors and hormonal factors, and all kinds of other things. So unfortunately, we can't draw a straight path between what these bacteria process and the actual activation of the headaches."
Dr Viirre and his colleagues are keen to do a prospective study to regularly track the incidence of headaches among patients as well as their bacterial flora.
"The key advance here is the capability to do these broad quantitative analyses of bacteria at relatively low cost; this is the genome project kind of spinoff."
Should this type of study bear out the connection between migraines and bacteria, there might be several plausible interventions, said Dr Viirre.
One possibility is to alter the bacterial flora. "In other words, if we figured out which species we wanted to promote, and we knew a way of doing that with diet, then we could do that."
A more aggressive step would be to actually intervene with chemicals instead of food, said Dr Viirre. "In future, we might be able to create chemicals that would enhance the growth of what we think are relatively important bacteria."
Perhaps antibiotics could be used in some way to alter the bacterial content in such a way as to create the proper balance. However, Dr Viirre stressed that at this point, these are all speculations.
This research was crowdfunded through individual contributions from American Gut Project participants.
mSystems. Published online October 18, 2016.^[1]

Breaking research, published in the journal mSystems, makes a surprising discovery regarding migraines. According to their findings, migraine sufferers have a significantly increased population of certain bacteria in their mouths.

Painful, debilitating, poorly understood: Migraine.

Migraines are a highly prevalent, painful, and disruptive condition.
Affecting an estimated 38 million Americans, the exact causes behind migraines are still unclear.
Some believe that the way in which the brain stem interacts with the trigeminal nerve (a major pain pathway) might be involved. It also seems that certain neurotransmitters, serotonin in particular, play a part in these changes.
Although the precise mechanisms involved in migraines are not known, a number of triggers have been identified, including hormone changes, physical exertion, weather, and stress.
Certain foods can also spark an attack, such as chocolate, processed meats, leafy green vegetables, and wine. One thing that these foods have in common is high nitrate levels.

Nitrates, nitrites, nitric oxide, and migraines

A group of researchers from the Center for Microbiome Innovation at the University of California-San Diego decided to investigate this fact in more detail, in an attempt to understand whether it plays a significant role in the development of migraines.
The team was headed up by first author Antonio Gonzalez and programmer analyst Rob Knight. The premise is explained simply by Knight: "We thought that perhaps there are connections between what people are eating, their microbiomes, and their experiences with migraines."
Nitrates, found in the foods mentioned above, are converted to nitrites by bacteria in the mouth; this is a normal process. Once nitrites enter the body, under certain conditions, they can be converted into nitric oxide.
Nitric oxide is known to help bolster cardiovascular health by improving blood flow and reducing blood pressure. For this reason, some cardiac patients are given nitrate-containing drugs to treat congestive heart failure and chest pain.
Of these patients, around 4 in 5 report severe headaches as a side effect of taking these drugs. Gonzalez and his team saw the potential connection and decided to delve into the details.
The team took data from the American Gut Project, one of the "largest crowd-sourced, citizen science projects in the country." From this database, Gonzalez and colleague Embriette Hyde, Ph.D., both of whom help manage the database at the Knight Lab, looked in detail at oral and fecal samples.

The microbiome and migraine

In all, they sequenced the bacteria found in 172 oral samples and 1,996 fecal samples of healthy participants. Each participant in the project had completed questionnaires at the start of the study; one question ascertained whether they suffered from migraines.
When bacteria from people who get migraines (migraineurs) was compared with non-migraineurs, there was little difference in the types of species present. However, importantly, there were differences in the abundance of some species.
The team used a technology called PICRUSt to examine the genes present in each of the bacterial samples. PICRUSt stands for "phylogenetic investigation of communities by reconstruction of unobserved states," and is pronounced "pie crust." It is a software designed to help researchers make sense of the function of genes taken from real-world samples.
In the migraineur group's fecal samples, there was a small, but significantly greater quantity of genes coding for nitrate, nitrite, and nitric oxide-related enzymes.
When the same comparison was made in the oral bacteria, the difference was even greater.

"We know for a fact that nitrate-reducing bacteria are found in the oral cavity. We definitely think this pathway is advantageous to cardiovascular health. We now also have a potential connection to migraines, though it remains to be seen whether these bacteria are a cause or result of migraines, or are indirectly linked in some other way."

Embriette Hyde, project manager for the American Gut Project

These new findings mark an important step toward understanding the role of microbes in migraine etiology. Whether they are a cause or effect, it is another piece to the puzzle.
Next, Gonzalez and Hyde want to widen their net; they plan to split the migraineurs into subgroups, such as those who experience migraines with aura and those who have migraines without aura, to investigate whether more patterns can be seen in the distribution of bacteria.
Read about an innovative sound therapy that can treat hypertension and migraine.

Written by Tim Newman

• We know that some foods can be migraine triggers for some people. It differs from one person to the next. Some people have migraines that can be triggered by several foods or beverages while some of us have no food or beverage triggers. We also have known for some time that certain foods such as hot dogs, lunch meats, other preserved foods, and leafy green vegetables can be triggers because of the nitrates in them. What we don't know is exactly why nitrates can trigger migraine attacks.
  
  Study results published in mSystems, the journal of the American Society for Microbiology suggest that certain bacteria found in the mouths of people with migraine may be responsible for nitrates being a migraine trigger. People who experience migraine attacks have more of this bacteria in their mouths than people who do not experience migraine attacks. The bacteria reduces nitrates to nitrite, which increases levels of nitric oxide. Higher levels of nitric oxide have been related to migraine in other research.
  
  The study authors concluded:
  

  "These results show for the first time a potential link between bacterial nitrate, nitrite, and nitric oxide reducers and migraines, by reporting their higher abundances in the oral cavities of people with migraines than in the oral cavities of those who do not suffer from migraines. Future studies should focus on further characterizing the connection between oral bacterial nitrate, nitrite, and nitric oxide reducers and migraines."

  In a CNN interview, Embriette Hyde, Ph.D., assistant project scientist at the University of California, San Diego School of Medicine and a coauthor of the study, said:
  

  "One can imagine a targeted treatment, such as mouthwash or the introduction of a probiotic species. However, this will be really complex. It's certainly a complicated puzzle."
  "While the link between migraines and nitrates has been known for a while, researchers still aren't sure about the nature of this link. We know it depends on eventual formation of nitric oxide, but the exact mechanism hasn't been established yet. This study is very preliminary, and while the findings are exciting, we need to confirm them in a larger, targeted cohort."

  William B. Young, MD, a migraine and headache specialist at the Jefferson Headache Center, also commented in the CNN interview, saying:
  

  "You're not just the person you are, you're also, medically speaking, the bugs that live in your gastrointestinal system, and that could play a part in a lot of medical diseases and possibly, according to the study, migraine. The problem with the study is correlation is not causation. It could well be other reasons why people with migraine have different gut bacteria."

  Comments and implications for patients:

  While the information from this study is interesting, it is very preliminary. As Dr. Young noted in his comments, the study shows a correlation between migraine and an increased amount of certain bacteria in the mouths of migraineurs, but it doesn't prove the bacteria to be the cause for foods containing nitrates to be migraine triggers.
  
• 
  This study has no immediate implications for patients. If future research shows the bacteria to indeed be a cause in nitrates triggering migraine, the long-term implications could be the development of a treatment to reduce the amount of bacteria and counteract the effect of nitrates in triggering migraine.
  
  

  Headache and Migraines

  IN A NUTSHELL...
  
• Do the parasite cleanse to kill Strongyloide and other parasites
• Zap
• Do dentalwork
• Do the bowel program
• Do the liver cleanse
• Do the kidney cleanse
• Remove food allergens 
• Cleanup your home and use clean body-care products
   

There are common headaches, sinus headaches, migraines, and others, the causes of all overlap a great deal.
Tooth infection, urinary tract infection, bowel problems, and a wormlet, Strongyloides are the common causes.
There are also allergic connections which include milk, eggs, citrus and salty foods. But the allergy-approach is difficult to put into practice. It is almost impossible to stay off these foods for long time periods. Eliminating bacteria and Strongy¬loides leads to a permanent solution.
Every migraine sufferer (100%) has high levels of this tiny worm. Perhaps it is really the special bacteria it brings with it that cause the blood vessels to seep or to spasm in the brain, causing pain. Zap it immediately.
Bacteria hidden under a tooth filling or root canal or in a space where once a tooth was pulled can be the cause. Staphylococcus aureus is a favorite, but various Clostridia, Streps and others are often seen, too. You don't feel pain from this small abscess because the pressure isn't building up inside it. It has found a way into your body—namely, your brain!—so no pressure builds up to alert you. Find an alternative dentist with experi¬ence cleaning cavitations and finding small hidden abscesses. If you get immediate relief from dental work, only to lose ground again later, the abscess may have formed again (they are notori¬ous for forming again). Go back to the dentist. Irrigate the dental wound site with white iodine (potassium iodide, 12 drops) or Lugol’s (6 drops) to ¼ cup water using a curved-tip syringe. Do not use iodine if you know you are allergic to it.
The colon is always a thriving mass of bacteria. It should be emptied at least twice a day to keep their levels down. Use the simple herb, Cascara sagrada, senna tea, or magnesium oxide tablets (2 to 3 a day) to help you eliminate frequently if your own regularity is lacking.
Gallstones in the liver and a congested liver are sources of bacteria, too. Do several liver cleanses and note the effect.
Is it the toxins made by bacteria or the inflammation from the bacteria or wormlets themselves that produces the headache? Certainly, one can eat the toxins by themselves in foods like yogurt, cheese, wine, sour cream and develop “royal” headaches. Stay away from these tyramine containing foods. Boil all your dairy foods to prevent Salmonellas and Shigellas from swimming into your beleaguered brain. Don't eat dairy foods that can't be boiled for ten seconds.
Headaches are also caused by toxins in your environment; especially things you breathe in. Household gas is the most common offender. You don't smell it after you get used to it! Gas pipes are notoriously leaky. Conducting gases through pipes with joints in them, where gases could escape, must be the most ludicrous of all modern “conveniences”.
When your vanadium test is positive, you have a gas leak that your body found, even though the gas company may not. Many gas companies use outmoded equipment to search for it. Four out of five gas companies miss the gas leak. Health Departments and building con¬tractors use modern equipment that detects even the tiniest leak; call them.
If you are a headache sufferer, fixing the pipes is not good enough. Switch from fossil fuels to electric. There will be many dividends. (Remember not to use candles as part of your lifestyle, nor to be a smoker.) Your air needs to be clean: clean of perfumes and colognes, clean of potpourri and air fresheners, clean of air sprays, pesticides, formaldehyde, freon, carpet and car odor, fireplace lighter, and of wood smoke.

Recent research performed at the University of California San Diego School of Medicine suggests that oral bacteria may be a potential contributing factor to the onset of migraines.
According to the study, the connection between oral bacteria and migraines may be nitric oxide, a cellular signaling molecule involved in many pathophysiological processes. Past studies have shown that increased levels of nitric oxide in the bloodstream may play a critical role in triggering migraine headaches as well as tension and cluster headaches. In this most recent study, researchers suggest that oral bacteria produce nitrites when they break down nitrates (a common food preservative), which can then be converted into nitric oxide in the bloodstream.

Breaking It Down

Certain foods like hot dogs, lunch meat, and bacon are processed with nitrates, which act as a preservative. When a person eats a food with nitrates, the bacteria in the mouth and saliva do what they are supposed to do: They break it down.
When bacteria eat sugar, they break it down into acids–which, as most healthcare professionals know, can ultimately dissolve tooth enamel and cause dental caries. With processed food, those same bacteria break the nitrites down to nitrates, which then get converted into nitric oxide in the bloodstream. And when circulating nitric oxide levels increase, it can trigger a debilitating migraine, tension headache, or cluster headache.

Balancing the Benefits of Nitric Oxide

We know that one of the best health benefits of eating dark green leafy vegetables is that they cause our bodies to produce nitric oxide, which has numerous benefits for the cardiovascular system. Nitric oxide has a relaxation effect on our vessels which can reduce blood pressure and reverse hardening of the arteries. That’s why many people with heart disease take nitrates.
But ask a room full of cardiac patients what their side effects are, and odds are you’ll hear headaches as a chief complaint.
So what’s the right answer? After reading this study, we’re inclined to ask more questions:

• Are people with with periodontal disease and/or high levels of pathogenic oral bacteria more prone to these nitric oxide-inducing migraines?
• Would oral probiotics have an effect on headache and migraine probability?
• Are there specific bacteria that produce more nitrites than others?
• Am I allowed to eat bacon, or not?

No definitive conclusions can be drawn from this study alone. However, it may give headache and migraine sufferers an extra reason to avoid heavily processed foods.

Oral Bacteria & the Human Microbiome

This research, along with hundreds of other ongoing studies, continue to explore the inextricable health link between the mouth and the rest of the body. These studies are on the leading edge of a paradigm shift in medical research that is focused on the the microbiome on and inside of each of us. Widespread research in this human biome suggests that these organisms can either benefit or destroy our health. Leading medical experts expect to find major medical breakthroughs from this new focus.
The AAOSH community is made up of human biome specialists and practitioners who are passionate about creating health and wellness for our patients and our communities. We keep our fingers on the pulse of science-based medical evidence so that we may develop the best tools and practices to achieve our goals of creating health.
Our 7th Annual Scientific Session features dental and medical experts who study the science, tools and best practices surrounding genetics, immunity, and the microbiome. Don’t be left behind! Join our mission to improve health and wellness in your own community.