The pathogenic oral–gut–liver axis: new understandings and clinical implications

ABSTRACT

Introduction

Oral health is closely related to extra-oral disease status, as may be represented by the manifestations of gastrointestinal and liver diseases.

Areas covered

This review focuses on the roles that the oral–gut or the oral–gut–liver axis play in the pathogenesis of inflammatory bowel disease, colorectal cancer, metabolic fatty liver disease, and nonalcoholic steatohepatitis. The discussion will begin with clinical data, including data from preclinical animal models, to elucidate mechanisms. We will also discuss ways to target oral dysbiosis and oral inflammation to treat gastrointestinal and liver diseases.

Expert opinion

Several studies have demonstrated that oral pathobionts can translocate to the gastrointestinal tract where they contribute to inflammation and tumorigenesis. Furthermore, oral bacteria that migrate to the gastrointestinal tract can disseminate to the liver and cause hepatic disease. Thus, oral bacteria that ectopically colonize the intestine may serve as biomarkers for gastrointestinal and liver diseases. Also, understanding the characteristics of the oral–gut and oral–gut–liver microbial and immune axes will provide new insights into the pathogenesis of these diseases.

KEYWORDS:

• Oral microbiota
• gut microbiota
• inflammatory bowel disease
• colorectal cancer
• metabolic fatty liver disease
• nonalcoholic steatohepatitis

Article highlights

• Oral bacteria can translocate to the gastrointestinal tract where they contribute to inflammation and tumorigenesis.

• Gut colonized oral bacteria can further disseminate to the liver and cause liver pathologies.

• Oral treatment has the potential to improve the gastrointestinal and liver diseases.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Authorship contributions

JI, SK, and NK contributed to the conception and design of the manuscript. JI and NK wrote the manuscript. All authors reviewed the manuscript and approved the final version.

Additional information

Funding

This work was supported by Japan Society for the Promotion of Science 19K17413 (to JI), Takeda Japan Medical Office Funded Research Grant 2019 18J02400 (to JI), the University of Michigan Center for Gastrointestinal Research NIH P30 DK034933 (to SK and NK), the Office of the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense through the Peer Reviewed Cancer Research Program under Award No. W81XWH2010547 (to SK), National Institutes of Health grants DK108901, DK119219, AI142047, and DK125087 (to NK).