Inflammatory bowel disease (IBD) affects an estimated three million adults in the United States, however, it’s exact cause is unknown. Now, researchers from the University of Michigan (U-M) Medical and Dental School may be one step closer to solving the mystery.
The new study, published in the journal Cell, has found that poor oral health may worsen IBD. The condition, which includes Crohn’s disease and ulcerative colitis, is characterized by inflammation of the gastrointestinal tract.
The cohort was led by Nobuhiko Kamada, PhD, assistant professor of internal medicine in the division of gastroenterology at U-M. "I decided to approach the dental school to ask the question, does oral disease affect the severity of gastrointestinal diseases?" said Kamata, who pointed to recent research that found people with IBD also had an overgrowth of foreign bacterial species in their guts, bacteria normally found in the mouth.
The mouse study laid out two pathways by which oral bacteria appears to worsen gut inflammation.
In the first pathway, periodontitis, or gum disease, leads to a dysbiosis in a normal healthy oral microbiome. The increase of bacteria causes inflammation to travel to the gut.
The researchers demonstrated that oral bacteria may aggravate gut inflammation, but it may not be the sole trigger of gut inflammation.
Looking at microbiome changes in mice with inflamed colons, Kamada said, "The normal gut microbiome resists colonization by exogenous, or foreign, bacteria. However, in mice with IBD, the healthy gut bacteria are disrupted, weakening their ability to resist disease-causing bacteria from the mouth."
The research team also found that mice with both oral and gut inflammation had significantly increased weight loss and more disease activity.
The second proposed pathway noted that periodontitis activates T cells (T lymphocytes) in the mouth. T cells play a major role in the adaptive immune system. These mouth T cells then migrate to the gut where they also cause increased inflammation.
The normal gut microbiome is balanced by inflammatory and regulatory T cells, however, Kamada said oral inflammation generates mostly inflammatory T cells that travel to the gut. When they are removed from their normal environment, they set off the gut's immune response, aggravating disease.
"This exacerbation of gut inflammation driven by oral organisms that migrate to the gut has important ramifications in emphasizing to patients the critical need to promote oral health as a part of total body health and wellbeing," said co-author William Giannobile, DDS, the William K and Mary Anne Najjar professor of dentistry and chair of the department of periodontics and oral medicine at the U-M School of Dentistry.
“Far too many patients still fail medications, leading to reduced quality of life and eventual surgery," said study co-author Shrinivas Bishu, M.D., assistant professor of gastroenterology. "This study importantly implies that clinical outcomes in IBD may be improved by monitoring oral inflammation — an intriguing concept."
In other words, a better understanding of the relationship between the mouth-gut axis and IBD may lead to oral microbiome modulation to get the root of the problem inside the gut.
182, 1–16 July 23, 2020 doi.org/10.1016/j.cell.2020.05.048
“The Intermucosal Connection between the Mouthand Gut in Commensal Pathobiont-Driven Colitis”
Authors: N. Kitamoto et al.