Unravelling the Oral-Gut Axis: Interconnection Between Periodontitis and Inflammatory Bowel Disease, Current Challenges, and Future Perspective

Abstract

As the opposite ends of the orodigestive tract, the oral cavity and the intestine share anatomical, microbial, and immunological ties that have bidirectional health implications. A growing body of evidence suggests an interconnection between oral pathologies and inflammatory bowel disease [IBD], implying a shift from the traditional concept of independent diseases to a complex, reciprocal cycle. This review outlines the evidence supporting an 'oral-gut' axis, marked by a higher prevalence of periodontitis and other oral conditions in IBD patients and vice versa. We present an in-depth examination of the interconnection between oral pathologies and IBD, highlighting the shared microbiological and immunological pathways, and proposing a 'multi-hit' hypothesis in the pathogenesis of periodontitis-mediated intestinal inflammation. Furthermore, the review underscores the critical need for a collaborative approach between dentists and gastroenterologists to provide holistic oral-systemic healthcare.

Keywords: Crohn’s disease; Periodontitis; dysbiosis; gum–gut axis; immune response; inflammatory bowel disease [IBD]; oral bacteria; oral–gut axis; ulcerative colitis.

Figure 1.

Schematic of IRF8 gene structure with previously reported IBD single nucleotide polymorphisms [SNPs], genotypic changes, and p values.

Figure 2.

One hit, not enough wit—a multi-hit model. [Red circle] The onset of periodontitis leads to an expansion of pathogenic oral bacteria. These bacteria can translocate to the intestine, either via ingestion or through the circulatory system. Normally, ingested oral bacteria are inactivated as they pass through the stomach. [Green circle] Several factors, such as genetic disorders, medications, diet, smoking, alcohol, ageing, and stress, may disrupt intestinal barrier function and shift the gut microbiota in the long-term. This disruption can reduce colonization resistance, facilitating the establishment of oral bacteria in the gut. [Blue circle] Once established in the gut, oral bacteria activate both innate and adaptive immune responses leading to intestinal inflammation. Oral dysbiosis or disrupted gut barrier alone are insufficient to predispose the host to IBD. Both a sufficient load of oral pathogens and disrupted barrier function are necessary for oral pathogens to successfully colonize the gut, which then activates immune responses leading to intestinal inflammation.

Figure 3.

Oral pathogen-mediated immune responses that drive gut inflammation in IBD. Periodontitis onset triggers expansion of pathogenic oral bacteria. Constant saliva swallowing enables these bacteria to translocate to the gut. A compromised intestinal barrier function, marked by diminished mucus and epithelial barrier integrity, facilitates the penetration of oral bacteria into the sub-epithelial regions. Neutrophils, the first responders, attempt to phagocytose the ingested bacteria and release antimicrobial substances. Additionally, the antigen-presenting cells [APCs] in the gut recognize the microbial invaders through pattern recognition receptors such as Toll-like receptors [TLRs]. Once activated, these cells release a cocktail of pro-inflammatory molecules: interleukin [IL]-6, IL-12, IL-23, IL-1β, tumour necrosis factor α [TNF-α], and chemokines. Consequently, these molecules guide the differentiation of naive T helper [Th0] cells into Th1, Th2, Th17, and Treg cells. Furthermore, B cells become activated by recognizing bacterial antigens and differentiate into plasma cells, which produce antibodies specific to the oral bacterial antigens. These antibodies neutralize or opsonize bacteria and can form immune complexes, intensifying inflammation. The concerted actions of innate and adaptive immune cells lead to initiation or exacerbation of the inflammatory process in IBD, highlighting the far-reaching effects of oral bacterial dysbiosis. Figure created with BioRender.com.