TMAO is a potential target for the association between periodontitis and inflammatory bowel disease


Intestinal inflammation and periodontitis are two distinct medical conditions that can affect different parts of the body but share a complex relationship. While intestinal inflammation primarily affects the gastrointestinal tract, periodontitis affects the tissues surrounding the teeth. However, recent medical studies have suggested that there might be a connection between these two conditions, indicating that inflammation in the gut can have implications for oral health. To understand the relationship between intestinal inflammation and periodontitis, it is important to delve into the underlying mechanisms and potential pathways that connect the two conditions. One of the key factors in this connection is the immune system. Both the intestines and the oral cavity are part of the mucosal immune system, which is responsible for maintaining a balance between tolerance to harmless antigens and defense against pathogens. When this delicate balance is disrupted, it can lead to chronic inflammation in both locations.

Intestinal inflammation is commonly associated with conditions such as inflammatory bowel disease, which includes crohn’s disease and ulcerative colitis. These conditions involve chronic inflammation of the intestinal lining, resulting in symptoms such as abdominal pain, diarrhea, and weight loss. Inflammation in the gut can trigger a systemic immune response, leading to an increase in pro-inflammatory cytokines and immune cells in the bloodstream. These immune mediators can travel to other parts of the body, including the oral cavity, and potentially contribute to the development or progression of periodontitis. Periodontitis is a chronic inflammatory condition that affects the tissues supporting the teeth, including the gums, periodontal ligament, and alveolar bone. It is primarily caused by the buildup of dental plaque, a biofilm composed of bacteria, on the teeth and gums. The interaction between the bacteria and the host immune response plays a crucial role in the progression of periodontitis. In response to the bacteria, the immune system releases inflammatory mediators, such as cytokines and chemokines, which contribute to tissue destruction and bone resorption.

Studies have demonstrated that individuals with intestinal inflammation, particularly those with inflammatory bowel disease, have a higher prevalence and severity of periodontitis compared to the general population. The systemic inflammation associated with intestinal inflammation can amplify the local inflammatory response in the gums and promote the progression of periodontitis. Additionally, alterations in the gut microbiota composition, commonly observed in individuals with intestinal inflammation, may have implications for oral health. An imbalance in the microbial community, in the gut can potentially impact the oral microbiota composition and favor the growth of periodontal pathogens. Furthermore, the immune dysregulation observed in intestinal inflammation may affect the host immune response in the oral cavity. The chronic systemic inflammation can impair the immune system’s ability to control the growth of pathogenic bacteria in the oral biofilm, thereby exacerbating periodontal inflammation. Additionally, the increased production of pro-inflammatory cytokines in individuals with intestinal inflammation can lead to higher levels of these mediators in the oral tissues, contributing to tissue damage and bone loss in periodontitis.

Trimethylamine-N-oxide (TMAO) is a metabolite produced by the gut microbiota from dietary compounds such as choline, betaine, and carnitine. While TMAO has been implicated in various physiological processes, recent research has shed light on its role in inflammation. TMAO has been associated with the promotion of inflammation, particularly in the context of cardiovascular diseases, metabolic disorders, and inflammatory bowel disease. Understanding how TMAO contributes to inflammation is crucial for comprehending its impact on human health. It is important to note that the effects of TMAO on inflammation are not limited to the gut. Once TMAO is absorbed into systemic circulation, it can exert its pro-inflammatory effects on various tissues and organs. It’s important to note that the relationship between intestinal inflammation and periodontitis is complex and multifactorial. While research suggests a connection, further studies are needed to elucidate the underlying mechanisms and causality. In a new study published in the peer-reviewed Journal Frontiers in Cellular and Infection Microbiology, Qiqi Wang and Professor Wenzhou Xu from Jilin University in collaboration with Dr. Yue Sun, Tianyu Zhou, Cong Jiang, Professor. Lan A from the Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering examined the role of TMAO in the gut-oral inflammation axis. The authors demonstrated that TMAO can indeed affect the process of periodontitis.

The research team evaluated the effect of a TMAO inhibitor (3,3-dimethyl-1-butanol (DMB)) in mice with no periodontitis and another group that has periodontitis. The authors examined the changes in intestinal histology, intestinal flora composition, periodontal tissue, and periodontal pro-inflammatory factors after 10 days and found significant reduction in intestinal inflammation where the Firmicutes number and the ratio of Firmicutes/Bacteroidetes were improved in the periodontitis group that administered TMAO. Firmicutes and Bacteroidetes are two major phyla of bacteria that reside in the human gut microbiota. These phyla are highly abundant and play essential roles in maintaining gut health and overall well-being. According to the authors, immunohistochemistry revealed higher levels of inflammatory markers of TGF-b and IL-1b expression in the periodontal tissues of periodontitis group that administered TMAO.

In summary, Professor Wenzhou Xu and colleagues examined the gut microbiome metabolite TMAO and its implication in the inflammation of intestinal-oral axis.  Understanding the contribution of TMAO to intestinal-oral axis inflammation is important for identifying potential therapeutic targets and developing strategies to mitigate its detrimental effects on human health. In a statement to Medicine Innovates Series, Professor Wenzhou Xu said: intestinal inflammation and periodontitis are two distinct conditions that share a potential relationship. The systemic inflammation and immune dysregulation associated with intestinal inflammation may contribute to the development and progression of periodontitis. Understanding this connection is crucial for healthcare professionals to provide comprehensive care and consider the potential impact of intestinal health on oral health.

TMAO is a potential target for the association between periodontitis and inflammatory bowel disease - Medicine Innovates

About the author

Wenzhou Xu received his Bachelor degree, Master degree and PhD degree at Jilin University.

He is currently the deputy chief physician and postgraduate supervisor of Department of Periodontology, School and Hospital of Stomatology, Jilin University. He is a visiting scholar at the Eastman Institute Oral Health Research of the University of Rochester in the United States. He is also a member of the Chinese Stomatological Association. Young member of the Pathology Professional Committee, member of the Periodontics Professional Committee of the Jilin Provincial Stomatological Association, and a national second-level psychological counselor.

As the first author or corresponding author, he published 8 high-level peer-reviewed SCI papers, presided over and participated in 15 national, provincial and ministerial projects. The current research interests of Dr. Xu’s team include: 1) the development and application of new treatments for periodontitis and peri-implantitis; 2) the study of periodontal microecology and the relationship between periodontal disease and systemic diseases.


Wang Q, Sun Y, Zhou T, Jiang C, A L, Xu W. Gut microbiota-dependent trimethylamine n-oxide pathway contributes to the bidirectional relationship between intestinal inflammation and periodontitis. Front Cell Infect Microbiol. 2023 ;12:1125463. doi: 10.3389/fcimb.2022.1125463.

Go To Front Cell Infect Microbiol.