Insights on the Gut Microbiome for the Canadian Health Journal
Have you ever heard your mother say, “You are what you eat”? Well, it turns out she was right about that too! As humans, we are more bacteria than we are human, which makes sense considering the first form of life on earth was bacteria. Yes, bacteria existed way before humans, even the dinosaurs. In fact, a human microbiome contains 150x more genetic information than the human genome. We also swallow 8×1010 bacteria a day (1). So between our various microbiomes and what we bring into our bodies, it is no wonder we are made up of mostly bacteria. What mom meant by ‘you are what you eat’ is two fold; we are mostly bacteria and what we feed that bacteria is important. If we want to be healthy, we need to feed our microbiome nutritious food. If we want to be sick, then we can cram sugar, gluten, and processed foods down our throats and ensure the unhealthy bacteria thrive. Nourishing our microbiome is important because our gut microbiome is the largest immune organ we have in our bodies and it can either work for us or against us. When our immune system and microbiome is working properly, our bodies are in homeostasis. When our immune system fails us and our microbiome takes over, well, that’s what happens to decaying bodies after death. If our immune system takes over and our bacteria cannot defend the body, the person ends up with IBS. So it serves us well to understand the biology of our microbiome so that we can appreciate its importance and nurture it for optimum wellness. In this article I will discuss the science behind our microbiome, the oral microbiome axes, and how clinicians can help patients be healthier.
Let us begin with the basics as they are fundamental to our overall understanding. We have several microbiomes; skin, nose/sinuses, lungs, mouth, gut, and genitalia. And while all are important, we are going to focus on the oral and gut microbiomes for this article. The word microbiota means the living organisms within a specific environment while microbiome refers to the collection of genomes from all microorganisms in the environment. The microbiota refers to the organisms while the microbiome refers to the microorganisms plus their structural elements, metabolites, and environmental conditions. Most of our gut microbiome is present in the distal colon, but there are species along the entire length of the gut (8). There are trillions of bacteria present from 1000 different species (8). So how do we obtain all of this bacteria? Researchers used to think the fetus was in a sterile environment while in utero. We know this is no longer true as bacteria can cross the placenta, cause a detrimental infection, or help begin the microbiome colonization process (2). This was discovered by examining the contents of meconium, the first bowel movement of babies after birth (2). Most exposures to bacteria in utero are minimal, thus the main event establishing our microbiome is during the birthing process. It is during the birthing process that they pick up the mother’s microbiome through the birthing canal. Here, they are exposed to the vaginal and maternal gut microbiome as they ingest a bit of fecal material during birth. As we begin our life, we are exposed to all of the bacteria in the environment around us; from our parents' sweet kisses, to the surfaces we touch, to the food we eat. The diversity and strength of our microbiome correlates with our immune system throughout life; when we are young and elderly, our microbiome is weak and lacks diversity, hence our susceptibility to disease. When you are fit and able to eat anything you want and have superhuman characteristics in your early twenties, you can attribute that to your peak microbiome.
An interesting point about the microbiome is that there is not one kind of healthy microbiome, in fact, it is highly variable from person to person and changes over time depending on someone’s environment, their diet, and their stress levels. Our microbiome adjusts to what our current needs are. What is important for health is having a diverse microbiome that can function as a robust immune system to keep our barriers (skin, gut lining, gingival tissues) intact so that everything is kept in its proper place. The last thing we want is for harmful bacteria in our mouth to end up in our gut and for our toxic fecal waste products leaking into our abdomen, but unfortunately, this is what is happening to billions of people. This is why people end up with rheumatoid arthritis, irritable bowel syndrome, periodontal disease and many other ailments. To simplify the physiology, the cells within our barriers are held together by tight junctions. Their job is to link up the cells within the barrier and act as a gate to prevent the passage of harmful substances in either direction past the barrier. When tight junctions are exposed to foreign irritants, our immune system attacks by creating an inflammatory response, the tight junctions loosen, and what is on the inside leaks to the outside. These irritants can be foreign bacteria or viruses, gluten, dairy, etc. Once outside the barrier, the immune system activates and begins causing inflammation and disease in various organ systems.
Another key component to having a robust microbiome is the production of short chain fatty acids (acetate, butyrate, and propionate). The bacteria in the gut digest fiber and resistant dietary carbohydrates to produce metabolites called SCFAs (8). These SCFA’s have several health benefits such as creating a very important mucous layer biofilm to protect our gut membranes from breaking down, aiding in glucose and lipid metabolism, helping our immune and inflammatory responses, regulating our endocrine system, and regulating our blood pressure (3). SCFAs also play a major role in the function of our enteric nervous system (ENS) which is the system responsible for secretion, movement, and absorption inside our gastrointestinal tract. With in the ENS, SCFAs “stimulate the sympathetic nervous system, cause mucosal serotonin release, and influence our memory, mental health, and learning processes.” (4) These really are miracle molecules and all come from digesting fiber! They will help us fight inflammation, prevent cancer, prevent heart disease, shield our liver from damage, save our brains, and help prevent diabetes and obesity (9). Ever hear of Ozempic? Ozempic’s active ingredient is GLP-1. Guess what naturally induces GLP-1 secretion…..SCFAs. Eat your fiber!
Let’s move to where it all starts, in the mouth. As oral health specialists, we should be particularly concerned with the oral microbiome as this is our area of expertise. The oral microbiome is a diverse one, comprising over 700 million bacteria from 700 different bacterial species (6). This is a collection of helpful, harmful, and commensal bacteria, viruses, protozoa, and fungi that act in communities and serve different purposes (11). When there is a proper balance between these different categories of species, the mouth is in homeostasis and is healthy. Disease will not exist. When communities of harmful bacteria thrive and over power good bacteria, diseases like caries, periodontal disease, and thrush occur. Again, diversity is important in an oral microbiome and the microbiome is as variable and vulnerable as the gut. However, there are common strains associated with health. Strains associated with periodontal health are Lactobacillus reuteri and Lactobacillus brevis. Strains associated with preventing cavities include many in the Lactobacillus family including L. acidophilus, L. reuteri, and L. salivarius, Bifidobacillus, and Streptococcus salivarius strains (7).
Our oral microbiome is connected to the rest of the body’s microbiomes because the main point of entry into the body is through the mouth! People are hyper obsessed with the gut microbiome (and they should be), but they never stop to think, “how did that bacteria even get there?” Common sense would lead us back to where it begins, in the mouth. Bacteria enter our body in two main ways, either by swallowing 80 trillion bacteria a day, or by entering our system through leaky gums, otherwise known as periodontal disease to dentists and hygienists. Our gum tissue is built in a similar way that our intestinal tract is built and is therefore affected in the same manner. Our gingival tissues are meant to close off our oral cavity, and everything in it, from our insides. When pathological bacteria, viruses, and fungi are present, our immune system activates and ventures to the oral cavity to halt the intrusion. Our immune system releases a collagenase enzyme, MMP8, to help cut through tight junctions in our tissues to allow our immune cells to reach the intended target. While this is helpful to fight infection, it causes the breakdown of the tight junctions in our collagenous tissues and therefore compromises our gingival barriers. This same enzyme is responsible for the tight junction breakdown seen in leaky gut. The result in the mouth is the loss of periodontium, leaky gums, and bacteremia. When clinicians talk about harmful bacteria in the mouth, they need to be worried both about what damage can happen in the mouth and what damage can occur in the rest of the body. The local and systemic implications of oral bacteria are related to the host's inflammatory immune response (10). The greater the host inflammatory response, the leakier the gums, the more bacteremia occurs, and the more systemic inflammation and disease results. A patient can have a severe oral infection, but if their host immune response is low, the gingival tissues will remain intact, and the infection will remain localized and affect mostly the oral cavity. If the patient has an elevated host immune response and an oral infection, widespread dissemination of inflammation and bacteremia will occur throughout the body. So, as clinicians, we need to look at harmful bacteria that are present in the mouth as well as the level of the host immune response, and treat both. Otherwise, the oral bacteria will disseminate and affect other organ axes within the body.
A major interaction between the oral microbiome and the body is the oral-gut axis. Since the oral microbiome helps to establish and maintain the gut microbiome, a disruption in the mouth causes dysbiosis within the gut. This is due to us swallowing bacteria and via leaky gums, as mentioned before. Our gingival tissues and gut barrier are destroyed by the same enzyme, MMP-8, which results in toxins and molecules translocating beyond their places of origin and causing systemic inflammation. Because of this collagenase enzyme, if someone has inflammation in their mouth, they will feel it in their gut and vice versa. This is why many inflammatory bowel diseases, such as Chron’s disease are often detected and seen as cobblestones in the mouth. Microscopically, patients with bowel diseases have been found to have oral bacteria present in their intestinal lesions (12). These bacteria cause an activation of the immune system, a breakdown of the intestinal lining, and leakage of undigested food particles and microbes containing the endotoxin lipopolysaccharide into our bloodstream. The immune system attacks these invaders by triggering an inflammatory response. A result of this systemic response is the attack of other parts of the body, including our joint spaces, leading to arthritis. It is very common for a patient to have bleeding gums, digestive issues (bloating, gas, IBS) and arthritic pain and swelling. There are several bacteria in the mouth, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythensis, and Prevotella intermedia that translocate to our guts, escape, produce antibodies that trigger inflammation and the resultant destruction breaks down our joint spaces attributing to rheumatoid arthritis, osteoarthritis, and gout. This was discovered after researchers examined the feces of untreated rheumatoid arthritis patients and found that 75% of them had the aforementioned oral bacteria in their feces (13). Fusobacterium nucleatum has been implicated in inflammatory bowel disease. Fn activates interleukin pathways that lead to the destruction of our protective mucosal barrier. Oral bacteria also affect the incidence and survivability of colon cancer. Fusobacterium nucleatum infection is responsible for 20% of colon cancer diagnoses. It does this by attaching to the lining of the colon and causing its breakdown. As the lining breaks down, the cells begin to mutate and differentiate into carcinogenic cells. The presence of Fn then enhances the proliferation of these carcinogenic cells leading to cancerous polyps. It is also documented that once the cancerous polyps form, they have four times the concentration of Fn than the surrounding tissue (14). Fn also increases the chances for colon cancer recurrence by making chemotherapy treatments less effective. Fn tends to concentrate inside the polyps, making it more difficult for chemotherapy to reach it. Pg compounds the damage of Fn. Patients with colon cancer have been found to have high levels of Pg in their mouths (15). Colon cancer patients have been found to have high levels of oral Fn, intestinal Fn, and high plaque/gingival indexes which links oral bacteria to colon cancer (15). We are just beginning to understand the implications of the oral-gut axis, but it is clear the oral microbiome affects bowel disease, arthritis, and colon cancer.
New research is emerging on the oral-bone axis. It has been discovered that hematopoietic stem and progenitor cells inside the bone marrow are affected by systemic inflammation and will show preference for differentiation into innate immune cells. Studies are showing that periodontal inflammation leads to adaptation of bone marrow cells into innate immune cells that are implicated in the complications of arthritis. Even worse, these bone marrow cells affected by periodontal inflammation have memory, and will hyper respond in the presence of future inflammation. Also, matured neutrophils and B cells will return with inflammatory memory to the bone marrow after fighting off invaders elsewhere in the body and influence the surrounding immature cells. Periodontal inflammation can trigger such effects. This is an important finding as it suggests oral inflammation can lead to a predetermined baseline of inflammation and an exaggerated host immune response which can lead to complications such as joint pain, swelling, and bone loss (16).
The final oral axis to mention for this article is the oral-brain axis. Our oral microbiome has been implicated in Alzheimer’s and dementia as well as mental health conditions. Our blood brain barrier is meant to protect our brains from intruders and is responsible for the brain's cholesterol production. Cholesterol is vital to the functionality of our brains because it lines our neurons and aids in signaling. However, the blood brain barrier can be broken down by many things, including inflammation, infections, smoking, and radiation. When this barrier is broken down, the brain’s cholesterol production gets disrupted and can lead to neurodegenerative diseases. A chronic oral infection will lead to systemic inflammation, the breakdown of the BBB, and the passage of Pg into the brain. Pg secretes a molecule called gingipains which leads to the formation of beta-amyloid plaques and tau proteins around neurons. This leads to the death of neurons and failures in signaling pathways, ultimately leading to Alzheimer’s disease. Researchers have found Pg in the cerebrospinal fluid in patients living with Alzheimer’s disease and in the brains of deceased Alzheimer’s patients leading them to this conclusion (17). Fn is also known to be able to cross the blood brain barrier and is responsible for exacerbating inflammation in the brain and accelerating the disease (18). There is a correlation between the oral and gut microbiomes and mental health. It has been well documented that patients that have periodontal disease and gut issues also have mental health issues. The gut microbiome communicates with the central nervous system through the vagus nerve and has profound effects on memory, depression and anxiety (4). In fact, treatment with probiotics containing Lactobacillus rhamnosus and Bifidobacterium longum have greatly been shown to reduce mental health issues (4). This should not be surprising since 95% of serotonin is produced in the gut (5). This enteral serotonin can act locally within the ENS or peripherally in the CNS affecting mental health. Therefore, we must keep our oral and gut microbiomes healthy to ensure our serotonin production is functioning properly.
While the oral microbiome affects other organ systems in our body besides those mentioned above, it is important to understand how patients can improve their microbiome to combat disease and what we as dentists can do to help our patients. Dentists and patients first must change their mindset around cleaning the mouth. It has been widely accepted that the best way to maintain great oral health is to use products that aim to kill 99.9% of bacteria. These products are advertised as antibacterial and antiplaque, but they are actually anti-health. We should not be aiming to kill all bacteria in the mouth because we need good bacteria to maintain our microbiome and ward off disease. Patients should use products that are gentle, are targeted specifically to harmful species, and are alcohol free so that it does not dry out the mouth which increases plaque and caries formation. As a profession and as a society, we were able to change our mindset from hard to soft toothbrushes for a more gentle approach to caring for our gums; my hope is we will apply the same logic to cleaning products. We should also aim at supporting our microbiome by nourishing it with prebiotic and probiotics. Prebiotics are a food source for the existing healthy bacteria and can be found in foods such as artichokes, leafy greens, legumes, onions, and any food with a high fiber content. Probiotics are meant to add new strains of bacteria to our microbiome. Fermented foods such as Kifer, kombucha, and yogurt are good examples. There are several supplement products on the market that can provide oral pre and probiotics for your patients. As clinicians, we need to spend the time to educate our patients how to properly clean their teeth and gums as well as how to nutritionally support their microbiome for health.
Now that we are aligned on the products to safely clean our mouths and the food sources to support our microbiome, let’s discuss some ways you can help patients while they are in your office. Salivary diagnostics is a must if you are interested in helping patients with their microbiome and their systemic health. Dentistry has been a highly subjective profession since its inception, but we now have tests that can help us quantify and detect the root cause of disease. Periodontal disease, which we now understand has detrimental effects on the body, is caused by several different types of bacteria. These bacteria have different structures and do not all respond to the same, one size fits all treatment. Several pathogens are resistant to mechanical debridement, the gold-standard of care in periodontal therapy. Instead, they are better eliminated by using chemical adjuncts and lasers. By not knowing what type of bacteria are present, clinicians can either be over or undertreating their patients. Clinicians can also use these tests to see if their treatment is being effective and as a way to monitor the progression of disease by repeating the tests. This is exactly what a physician does when she orders for a complete blood count or an HbA1C test for diabetes. We must begin to think more like oral medicine specialists and use the diagnostic modalities available to us. Additionally, clinicians must actually look for gum infection, and since the only method to detect gum infection besides a saliva test is by using a dental probe, completing a full periodontal exam at every recall appointment is a must to catch disease early. Periodontal probing is the only way to detect pocketing (at this time), bleeding, and recession. If a clinician is not probing, they will miss disease and disease progression. We know that once the periodontium is lost, it is nearly impossible to regain any of it back, so we must be proactive and preventative by completing a periodontal exam at every recall appointment. If we see infection early, we can treat it and hopefully prevent the patient from a lifetime of disease management. Finally, as a profession, we must understand the gravity of periodontal disease and its effects on the body and begin to treat it with respect. This means treating the disease the moment it is caught, not waiting six months and hoping the patient will cure the disease by improving their oral health routine. We know that the majority of patients have a difficult time changing their habits, and if disease has set in, prolonging treatment is allowing for disease progression. Further, by telling the patient you are going to ‘wait and see in six months’ how their gums look, this is conveying a message that their condition is not urgent even though the science says it is.
This is an exciting time in the field of dentistry because the science is now available showing just how important oral health is to overall wellness! Dentists, physicians, and patients are becoming aware of this important connection and are seeking out knowledge and ways to improve their health. We can step in and help patients achieve health by educating ourselves on the oral systemic link, integrating technologies and best practices into our clinics, and by treating this disease seriously. Now is our chance to integrate the mouth back into the body and become oral medicine specialists.
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