Mighty mouth: the gut-mouth axis in treating GI diseases
Forgetting to brush or floss your teeth can lead to periodontitis, also known as gum disease. This disease is often caused by bacterial infection in the gums and could ultimately cause gums to recede, damage to bones in the mouth, and even tooth loss. Diseases of the mouth don’t happen in isolation and they have the ability to impact other parts of your body. Evidence is increasingly supporting the idea that the mouth-gut axis may contribute to the development of gastrointestinal diseases like irritable bowel disease (IBD) and Crohn’s disease. While these observations are gaining support, scientists have been able to gather only bits and pieces of information about how the mouth-gut axis contributes to disease in the gut.
One major contributor to infection in the mouth affecting the gut is the physical connection of these locations in the body, making it easy for disease-causing bacteria in the mouth to migrate and cause damage in the gut. Another thing known about diseases of the gut, like IBD, is that T helper cells, which are typically protective against bacteria, accumulate in the intestinal lining and contribute to gastrointestinal disease by causing inflammation. A key piece of missing information is what causes T helper cells to become enriched in the intestine of those with gastrointestinal diseases.
In order to examine how an inflammatory oral condition like gum disease could contribute to the accumulation of T helper cells in the gut, scientists first needed to evaluate which changes in microbes may be encouraging these immune cells to collect in the gut. In order to identify how microbes are changing in response to gum disease, scientists induced this disease in mice by tightly binding a tooth. With this method, they were able to compare changes in the oral and gut microbes of mice with or without gum and gastrointestinal disease. They found that mice with gum disease had increases in pathogenic oral bacteria. These bacteria were also more abundant in the guts of mice with gum disease and colitis, a disease characterized by inflammation of the gut. It is worth noting that these oral pathogens did not accumulate in the gut of mice that only had gum disease, suggesting that lack of intestinal inflammation and the presence of healthy gut microbes can prevent oral pathogens from taking up residence in the gut.
The presence of microbes not typically found in the gut can cause an immune response by cells that patrol their environment for invaders. One type of these immune cell is the macrophage, which eat foreign microbes and can recruit other immune cells if a threat is encountered. Macrophages also play an important role in regulating immune responses through their ability to secrete signaling molecules that aid communication between cells. The scientists behind this paper found that macrophages in the gut produce IL-1β when encountering oral pathogens. This information is noteworthy because previous work identified that IL-1β stimulates inflammation and promotes colitis, and oral pathogens which have migrated to the gut may play a role in initiating the inflammatory response.
When the authors examined the gut lining for immune cells, they found an increase in T helper 17 (Th17) cells in mice with both gum disease and colitis compared to mice with colitis alone. Th17 cells have an important role in defending the body against pathogenic bacteria and the Th17 cells from this study were reactive to pathogenic bacteria in the mouth. The scientists were curious about the ability of Th17 cells to transition from the oral cavity to the gut, and they determined that Th17 cells reactive to oral pathogens could successfully migrate to the gut. Not only was migration possible, but the Th17 cells that moved to the gut increased inflammation when they encountered oral pathogens that had also taken up residence in the gut. The authors wondered if introducing Th17 cells reactive to oral pathogens would cause gut inflammation in the absence of oral microbes and they found that was not the case. This suggests that the response of oral-reactive Th17 cells to oral pathogens in the gut, and not normal gut microbes, contributes to the inflammation characteristic of some gastrointestinal diseases.
By carrying out this work, scientists were able to reveal a bit more about how oral diseases, like gum disease, contribute to disease at locations far from the mouth. This paper suggests that proper oral care has the potential to reduce gastrointestinal disease risk, and also expands existing knowledge about the ability of specific types of immune cells to migrate to the gut from other sites in the body. Our understanding of the mouth-gut axis is just beginning and may provide a starting point for better treatments of gastrointestinal diseases.
By Fauna Yarza
Link to the primary paper here
Schema depicting the different connections between bacteria and the immune system in the mouth-gut axis. From the primary paper, Kitamoto et al.