I haven’t spent much time writing about the oral microbiome on this blog, mainly because most research has until recently focused on the microbial flora of the intestinal tract. It is the colon, after all, where the largest colonies of microbes, both beneficial and pathogenic, reside.¬†But the mouth harbors the second largest quantities of bacteria in the human body and it is becoming increasingly clear through metagenomic analysis that these microbes are capable of colonizing other areas of the digestive tract as well as directly entering systemic circulation thus triggering the Inflammatory-Cortisol Ballet.

It’s been recognized for many years that oral dysbiosis in the form of periodontal disease has a very high correlation with a number of disease states such as depression (1), cardiovascular dysfunction¬†(2), pancreatic and colorectal cancers, type two diabetes, Alzheimer’s disease and¬†respiratory tract infections. (3) But another disease showing a very high association with oral dysbiosis is rheumatoid arthritis, the subject of today’s post. (4)

It should come as no surprise to my readers that these seemingly disparate diseases are often found together in the same person. For example, depression and type two diabetes both show a high correlation with cardiovascular disease and rheumatoid arthritis. And the reason for this is that all aforementioned disorders are the result of chronic inflammation fueled by a dysbiotic digestive tract.

Rheumatoid arthritis is an autoimmune disorder that afflicts approximately 1.3 million people in the U.S. alone. Worldwide, rheumatoid arthritis is believed to bedevil the lives of 1% of the entire human population and its incidence is on the rise everywhere.

According to the Mayo Clinic, rheumatoid arthritis is characterized by:

  • Tender, warm, swollen joints
  • Joint stiffness that is usually worse in the mornings and after a period of inactivity
  • Fatigue, fever and loss of appetite

Early symptoms affect the small joints in the hands and feet. As the disease progresses, it begins to progressively affect the wrists, knees, ankles, hips, elbows and shoulders. And unlike osteoarthritis that may affect only one knee or ankle at a time, rheumatoid arthritic symptoms are symmetrical meaning that they usually affect both knees or ankles at the same time making everyday tasks difficult, to say the least.

Many people afflicted with this autoimmune disorder experience flares and remissions that are seemingly random. Over time rheumatoid arthritis often results in deformed joints which are especially noticeable in the hands and feet.

Like all autoimmune diseases, rheumatoid arthritis does have a genetic component. Possessing histocompatibility complex HLA-DRB1 is the most well-established genetic risk factor for developing this autoimmune disease. (5)

That said, genetic susceptibility cannot account for the recent increase in prevalence. Nor can it account for the fact that not every person carrying this genetic risk factor comes down with the disorder or for the fact that remissions can and do occur with some regularity.

One of the earliest clues that microbial pathogens from the oral cavity might play a role in rheumatoid arthritis comes from a case study first published in 1918. The paper recounts the experience of an engineer in his 40s afflicted with rheumatoid arthritis who went into remission after treatment for periodontal disease. Now periodontal disease is defined by Taber’s Medical Dictionary as:

“A disease of the supporting structures of the teeth, the periodontium, including alveolar bone to which the teeth are anchored. The most common initial symptom is bleeding gums, but loosening of the teeth, receding gums, abscesses in pockets between the gums and the teeth, and necrotizing ulcerative gingivitis may be present as the disease process worsens.”

Let me quote at length from this 1918 paper:

“The patient, Mr. B., aged about 45, consulted me on June 28, 1917. He was unable to walk, and could only move about with assistance and with the aid of crutches; his knee-joints were very much bent and perfectly rigid. He had been in that condition for a considerable time (how long I did not ascertain), and informed me that the doctors in attendance attributed his arthritis to septic absorption, the only source of which was his mouth, and that there was a question as to the advisability of extracting all his teeth, which were perfectly sound and not loose. He had been treated for pyorrhoea by vaccine therapy, the predominating organism being the streptococcus from which the vaccine was prepared; but this seems to have had very little effect on his arthritis, although the state of his gums seemed to have made improvement. His teeth were perfectly clean as far as the gingival border, the gums looked fairly healthy, there being only a fringe of redness¬†about the lower incisors and a purple hue about the lingual surfaces of the molars. The patient worried over his condition a good deal; he brushed his teeth several times a day and used peroxide of hydrogen freely. There was no visible pus anywhere, and if this constitutes a cure of pyorrhoea by vaccine therapy, a cure might be claimed here, and I suppose this is the appearance of the mouth when cures are claimed under similar conditions.

But examination of the gingival trough revealed the true state of things: there was a hard brown crust of ceruminal calculus encircling the roots of the teeth, from which the periodontal membrane had receded, forming shallow pockets. These pockets were singularly free from food debris. The irritant here was the calculus, which was quite out of sight, and had kept the gingival fold and periodontal membrane in a state of inflammation, as was evident from the bleeding which occurred when an instrument was passed into the trough. Tissues in this condition readily become infected, the toxins passing into the system through the bony channel, and it is by no means essential that pus should be present.

In my opinion the toxeemia had never been eliminated at the source; the infection at the alveolar border had kept up a constant supply of streptococci unaffected by the vaccine. Although the clinical appearance of the gingiva appeared to indicate a great improvement after six months of treatment, there being no pyorrhoea in the true sense of the term, still the patient was making no progress.

The treatment carried out consisted in removing every particle of calculus and polishing the root surfaces; this was no easy matter on account of the hardness and tenacity of the deposit. At each siting ionization of the gingival trough and alveolus was carried out with zinc ions, the patient being a good electrical subject, a current of 5 to 10 ma. was tolerated and the tissues yielded immediately to the treatment.

On August 10 he was discharged, every sign of inflammation in the gingival trough having disappeared. Three months later the pockets were examined and found to be in the same healthy condition. A decided improvement had taken place in the rheumatoid affection: the patient could walk across the room without crutches; although his knees were still bent and stiff, he nevertheless expressed his conviction that he was progressing favourably.

On June 10, 1918, when he was last seen (that is, ten months after treatment) the gingival trough was perfectly healthy, he had long since discarded the use of crutches, his knees were almost normal in shape, only as light stiffness remaining; he was able to walk long distances and had resumed his occupation as an engineer.” (6)

Now as fascinating as this case is, it’s still anecdotal and as the saying goes, the plural of anecdote is not proof. Perhaps his remission was totally coincidental to his dental treatment. Maybe he was going to experience a remission regardless of what the dentist did or didn’t do. As there was no control, it’s impossible to say. Nor do we know if the remission lasted.

But a case study like this can nonetheless be useful for forming hypotheses. And since 1918, the evidence of a link between oral/gut dysbiosis and human disorders of all types continues to mount as I’ve covered elsewhere on this blog. So from what you’re about to read, it appears that our early 20th-century dentist was clearly on to something even if the causative bacteria identified was incorrect.

As periodontal disease is the oral dysbiosis most closely associated with rheumatoid arthritis onset, it stands to reason that studying the gram-negative bacteria at the heart of this disease is the place to begin. That microbe is called Porphyromonas gingivalis or P. gingivalis for short. I’m sure most of you have noticed that this bacteria lends its name to the disorder known as gingivitis or inflammation of the gums.¬†P. gingivalis is¬†considered a keystone pathogen in oral dysbiosis development because although underrepresented in the oral microbiome, it can readily create an inflammatory environment in the mouth that fosters the growth of other oral pathogens. Now recent studies have implicated loss of immune tolerance toward citrullinated proteins in the etiology of rheumatoid arthritis and this is where what P. gingivalis does becomes of interest.

Citrullination is a process where the amino acid arginine is converted into the amino acid citrulline. This transformation is catalyzed by an enzyme known as peptidylarginine deiminase or PAD for short. And it is this enzymatic transformation that helps form rigid structures like skin, myelin sheaths and synovial membranes in our joints and tendons.

It is these citrullinated proteins that the immune system attacks both in rheumatoid arthritis and multiple sclerosis. In the first case inflaming and disfiguring joints and in the other destroying the protective covers of nerve cells in both the brain and spinal cord.

But what does any of this have to do with P. gingivalis?

Well, it produces a similar enzyme to human-generated PAD called PPAD that also catalyzes a citrulline-like structure that the immune system, however, identifies as an epitope. An epitope is that part of an antigen that an immune cell attaches to in order to attack it. Picture a neon sign that says eat me to which an immune cell happily obliges. Sadly for those afflicted with either rheumatoid arthritis or multiple sclerosis, the immune system not only attacks these citrullinated structures made by P. gingivalis wherever they might occur, it also begins attacking those same human created protein structures in joints and myelin sheaths. (7)

Fooling the immune system via molecular mimicry to attack self tissue is not the only downside to P. gingivalis, however. It, along with another gram-negative buddy by the name of Prevotella nigrescens (P. nigrescens), specifically induces the production of pro-inflammatory Th17 immune cells. These inflammatory cells are central not only in rheumatoid arthritis development, but you guessed it, to the onset of multiple sclerosis. And those suffering from psoriasis also experience elevated Th17 cell activation, which makes perfect sense when you consider the high association of this autoimmune skin disorder with cardiovascular disease, a disease that in my humble opinion should also be properly classified as an autoimmune disorder. (8)

Because P. gingivalis is a keystone pathogen, it utilizes other pathogen helpers to help do its dirty work. Along with P. nigrescens, P. gingivalis is often found in the same unsavory company with gram-negative bacteria like Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Anaeroglobus geminatus (A. germinatus) and various species of both the Prevotella and Leptotrichia genera.

In those newly diagnosed with rheumatoid arthritis, Prevotella species, Leptotrichia species and A. germinatus were found in teeming quantities in contrast to healthy controls. (9) Surprisingly, P. gingivalis was not discovered to be positively associated with early onset rheumatoid arthritis but only with the severity of periodontal disease thereby cementing its role more as a promoter of inflammatory environments ideal for other oral pathogens to thrive in.

Another curious finding is that the commensal bacteria Lactobacillus salivarus (L. salivarus) is found in higher numbers in rheumatoid arthritis patients than in healthy controls. Why this is the case remains a mystery, but it may behoove anyone afflicted with rheumatoid arthritis to avoid consuming this particular probiotic.

There is also increasing evidence that oral bacteria can travel to other parts of the body including the joints. One obvious way of entering systemic circulation is via bleeding gums. P. gingivalis can also survive within certain immune cell types like macrophages and dendritic cells thereby making its way to distant parts of the body. (10) (11) The DNA of other oral pathogens like P. intermedia and F. nucleatum have also been discovered in the synovial fluid of rheumatoid arthritis patients with periodontitis. (12)

But humans also continuously swallow bacteria with or without food, which is why the gastric barrier is so essential to maintaining gut and overall health. But as I explained in my Acid Reflux Series¬†there are a number of practices and drugs that undermine this very important barrier function so it’s little wonder oral bacteria is being increasingly detected in the feces of humans.¬†This is particularly alarming in light of the fact that P. gingivalis, A. actinomycetemcomitans and F. nucleatum have all been implicated as possible instigators of pancreatic and colon cancers. (13)

As these pathogens are all gram-negative, everything I’ve previously written about endotoxemia would be true of these pathogens should they colonize the intestinal tract. In one experiment, administering P. gingivalis¬†to mice led to a number of negative effects on the guts of these animals. (14)¬†For example, the Bacteroidetes phylum was reduced in number while the proportion of Firmicutes was elevated. But most ominously, the complexity of the gut microbiome was significantly lessened in these animals. As I’ve stated on numerous occasions, a healthy gut flora is a diverse gut flora so anything that reduces this microbial diversity is going to have negative effects on wellness.

P. gingivalis colonization of the intestines has been found to impair gut barrier function by upregulating the expression of pro-inflammatory genes. This would lead to increased intestinal permeability or leaky gut. It also significantly leads to increased Th17 immune responses that aggravate arthritis symptoms, not surprising given its inflammation provoking characteristics.

P. gingivalis also increases the proportion of Prevotella species in the gut and it appears to do so by decreasing Bacteroidetes. (15) Prevotella species are known to suppress anti-inflammatory Treg cells that balance inflammatory Th17 cells. For example, Prevotella copri (P. copri) has been linked to increased Th17 inflammatory immune responses in rheumatoid arthritis. (16) Antibodies to P. copri have also been detected in many newly diagnosed rheumatoid arthritis patients. (17)

What To Do

So what should you do if you are one of the millions suffering from rheumatoid arthritis?

Well, the first thing I would suggest is to have your mouth thoroughly screened by a dentist for periodontal disease. Untreated periodontal disease should be suspected in anyone with rheumatoid arthritis even if your gums appear healthy to you.

Secondly, you should assume that P. gingivalis and other gram-negative oral pathogens have already colonized your gut and that you suffer from endotoxemia. You will therefore also need to treat any underlying gut dysbiosis.

There are certain probiotics that have been shown to tamp down inflammatory immune responses by acting directly on the immune system or by strengthening gut barrier function. Probiotics like Lactobacillus casei (L. casei) and Lactobacillus rhamnosus (L. rhamnosus) have both shown anti-inflammatory properties and should therefore be part of any protocol to combat this autoimmune disorder. (18) (19)

Along with probiotic supplementation (whether through pills and/or fermented foods like yogurt or kefir) it is also imperative that prebiotic fiber be included in the diet. It would not surprise me in the least to discover that butyrate, a metabolite of prebiotic metabolism by commensal colonic gut flora, is chronically low in those suffering from this disease. As I’ve written on numerous occasions, butyrate is important not only for gut wall integrity but also for maintaining the integrity of the blood-brain barrier.

What To Avoid

Cigarette smoking has been shown to increase the incidence of rheumatoid arthritis in both men and women. (20)¬†(21). This isn’t surprising as smoking increases the incidence of periodontitis by shifting the oral microbiome to a pro-inflammatory pathogenic state hence its high association with heart disease. So at the risk of stating the obvious, those smokers suffering from any autoimmune disorder whether it be rheumatoid arthritis or another need to quit for any chance of lasting remission.

Alcohol is another known risk factor likely due to its effects on oral flora as well as gastric acid levels. As I wrote in my post Alcohol and the Gastrointestinal Tract:

“Alcohol is a very effective bactericidal because it easily disrupts the lipid membrane that encases bacteria. Sadly, however, the alcohol you drink has no magical ability to differentiate between beneficial or harmful oral bacteria. It just goes about its business popping bacterial membranes without a care in the world.

While oral bacteria like gut flora is fairly resistant to bactericidals much as gut flora is somewhat resistant to short courses of antibiotics, there are limits. Limits that are dose dependent, and therefore partly explain the horrific state of dental and oral health that afflicts many who abuse alcohol.

Alcohol, apart from effects on oral bacteria, causes direct injury to the mucosal lining of the mouth, throat and esophagus, inviting inflammation and bacteria that thrive in inflamed conditions. Chronic and acute alcohol intake damages the salivary glands and causes interference with saliva secretion. (5) As saliva contains lactoferrin, a glycoprotein that inhibits the growth of oral pathogens, the risk of oral dysbiosis rises with increasing alcohol intake. (6)

Alcoholics and binge drinkers often suffer from glossitis, inflammation of the tongue, as well as stomatitis, inflammation of the mouth. Whether these effects are due to alcohol or its metabolite, acetaldehyde, is still unclear.”

And as for alcohol’s effect on gastric barrier function:

“Alcohol‚Äôs effects on stomach function are both dependent on alcohol type and dose. In healthy, non-alcoholic subjects, administration of 0.3 to 0.5 grams of alcohol at concentrations of 5% stimulates gastric secretion. However, this is only true for fermented alcoholic beverages like wine, beer, champagne and sherry. Distilled alcoholic beverages like vodka, rum and whiskey do not increase acid secretion. (17)

…stomach acid serves a very important barrier function by killing swallowed bacterial pathogens thus preventing them from making their way to your intestine and taking up residence. As ingesting fermented alcoholic beverages like wine and beer increases stomach acid secretion, we would expect this barrier function to be enhanced by small to moderate consumption of these fermented beverages.

At higher doses, however, this beneficial effect disappears. High alcohol consumption, regardless of type, results in an increase in stomach alkalinity that compromises not only your ability to kill swallowed pathogens, but also your capacity to properly digest protein.”

Last, but certainly not least, diet change must be considered an important component of any protocol relating to the treatment of both oral and gut dysbiosis. It should go without saying that sugar consumption should be kept to less than 10% of calories as most cohort studies have shown a dose-dependent increase in tooth decay with increasing sugar consumption, and that obviously includes consumption of high fructose corn syrup. (22)

In a meta-analysis of 55 papers examining sugar consumption and cavity formation mostly in children, 42 out of 50 and five out of five in adults reported at least one positive association between ingesting sugar and tooth decay. But these types of studies are inherently unable to prove causality given their nature, which is why the quality of evidence was graded moderate at best.

Now while I do consider limiting sugar consumption a plus, it certainly did nothing for me when I was afflicted with persistent dental plaque. I’d consumed little to no added sugar for at least two decades but was still forced to have my teeth cleaned every three months to prevent the development of carpal tunnel syndrome in my dear, overworked dental hygienist.

So I cannot stress enough how important reducing or eliminating the consumption of gluten grains is to the whole process of battling both oral and gut dysbiosis. Apart from the dysbiosis promoting effects gluten exorphins have on stomach emptying and intestinal peristalsis, gluten’s effect on dental biofilm formation must not be overlooked.

I don’t consider it a mere coincidence that the oral biofilms, ie. plaque, that bedeviled me my entire life disappeared once I gave up eating wheat and other gluten-containing foods all while my brushing and flossing habits remained unchanged. But as this is the very definition of anecdote, I don’t expect anyone to take my word for it which is why I want to briefly discuss a 2013 Israeli paper studying the effects of a gluten-free diet on dental health in children diagnosed with celiac disease.¬†(18)

This study was simultaneously revealing and somewhat humorous (yes, I’m easily amused). Revealing because the children who had been on a gluten-free diet showed the least tooth and gum disease in comparison to newly diagnosed celiac kids and a control group that stood in for the typical Israeli child. In fact, the children with the worst dental health of the three groups were the “healthy” wheat eating controls. But what made this paper humorous was that the researchers did everything in their power to ignore the awkward truth as you’ll read in a minute.

I think we can all safely assume that Israeli children, much like their American, European and Asian counterparts, are not as a rule binge drinkers or three-pack-a-day smokers, so we can safely ignore those causes for their abysmal oral health. And I don’t believe these differences can be solely explained by variances in sugar consumption. While the gluten-free children are no longer able to consume sweets like cakes, pies, cookies, donuts, etc., I’m sure they’ve found adequate sugary substitutes to take their place as kids are wont to do with or without their parent’s permission. And many gluten-free substitutes on the market these days are just as sugar-laden as their wheat-containing originals.

So it seems evident to me that the reason the gluten-free children had better oral health has to do with the obvious fact that they were no longer consuming a grain flour that when moistened by saliva becomes quite sticky thereby helping to cement bacterial biofilms to the sides of teeth while simultaneously providing a rich nutrient source for their proliferation.¬†Let’s not forget that the modeling compound known as Play-Doh that we all played with as children¬†is mainly composed of flour, water and¬†some oil. Before being sold to our parents as a fun toy to entertain us with, it was originally marketed as a cleaner in the 1930s for its sticky ability to lift coal residue off wallpaper. (19)¬†And as any baker knows, you need to constantly flour your rolling pin and counter to avoid having dough stick to surfaces. It is this tacky, adhesive property of wheat flour even after baked that most likely explains gluten’s promotion of biofilm formation on dental structures.

Furthermore, its propensity to induce intestinal dysbiosis via exorphin formation and wheat germ agglutinin ingestion can also not be overlooked. A dysbiotic small intestine is not capable of properly absorbing nutrients essential to dental health like vitamin A, vitamin D, phosphorus and calcium.

But what appears obvious to me seems to have flown right over the heads of these researchers hence the unintended humor. To quote them directly:

“Surprisingly, the rate of enamel hypoplasia (tooth decay) in the control group was higher than expected. This finding may be an anomaly. We have no explanation as to the higher rate of enamel hypoplasia in Israeli children and it warrants further studies to assess the rate of enamel hypoplasia in Israeli population.”

No explanation?

Not a clue?


A particularly gut-busting paragraph is this one that leads with a hypothesis in the first sentence that’s promptly rejected by the last:

“The difference in the oral hygiene among the groups that resulted in less dental caries in the GFD-treated group [gluten-free diet treated group] may be attributed to differences in socioeconomic background. Data to assess this issue were not collected initially, but when looking at the origin of the patients, most families lived in the 3 major cities around the medical center with similar socioeconomic background. Furthermore, because dental care and education is available free by law to all Israeli children, it is unlikely that low economic status will preclude children to access adequate dental care; however, these issues should be addressed further in future studies.”

So if socioeconomic background or access to dental care isn’t the explanation, what oh what could it possibly be I wonder?

Toothbrushing claim these researchers, toothbrushing!

But when you look at their actual data, it appears highly unlikely that brushing could possibly explain anything. We see from their own figures that 2 kids in the control group did not brush their teeth daily as opposed to 0 in the gluten-free group, 10 kids in each group brushed once a day and 18 kids in the control group brushed twice a day as opposed to 20 kids in the gluten-free group. These differences are so minute as to be statistically irrelevant, but when you’re grasping at straws to absolve our daily bread in the biblical promised land no twig is apparently too small to grasp!

This myopia against implicating gluten-grain (wheat) consumption as deleterious to human health outside of celiac disease so permeates the assumptions of contemporary nutritional “science” and medicine that these researchers couldn’t possibly entertain the thought that perhaps the reason for the better dental health in the children consuming a gluten-free diet was due to—wait for it—not eating fucking wheat!

Astonishing, simply astonishing!


As I’ve written before and will no doubt write again, keeping your digestive gut flora healthy is overwhelmingly reliant on what you eat much like the performance of your car’s engine is reliant on the type and quality of the fuel you put in the tank and the oil you put in the crankcase. And while I remain a very big proponent of frequently ingesting probiotics and prebiotics (whether from fermented foods,¬†probiotics, prebiotic powders, soluble fiber containing plant foods, etc.), the fact remains that the quality of one’s diet is paramount to the state of your oral and gut flora and by extension your overall health. Therefore anyone expecting a magic pill, powder, potion or medical procedure to save them from a bad diet and resulting dysbiosis is ultimately on a fool’s expressway to a miserable end.


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