Role of oral and gut microbiome in nitric oxide-mediated colon motility

Abstract

Periodontal disease (PD), a severe form of gum disease, is among the most prevalent chronic infection in humans and is associated with complex microbial synergistic dysbiosis in the subgingival cavity. The immune system of the body interacts with the microbes as the plaque extends and propagates below the gingival sulcus. Once bacteria reach the gingival sulcus, it can enter the blood stream and affect various areas of the human body. The polymicrobial nature of periodontal disease, if left untreated, promotes chronic inflammation, not only within the oral cavity, but also throughout the human body. Alterations seen in the concentrations of healthy gut microbiota may lead to systemic alterations, such as gut motility disorders, high blood pressure, and atherosclerosis. Although gut microbiome has been shown to play a vital role in intestinal motility functions, the role of oral bacteria in this setting remains to be investigated. It is unclear whether oral microbial DNA is present in the large intestine and, if so, whether it alters the gut microbiome. In addition, polybacterial infection induced PD reduced nitric oxide (NO) synthesis and antioxidant enzymes in rodent colon. In this review, we will discuss the interactions between oral and gut microbiome, specifics of how the oral microbiome may modulate the activities of the gut microbiome, and possible ramifications of these alterations.

Keywords: Antioxidants; Colitis; Gut motility; Microbiome; Nitric oxide; Periodontal disease.

Fig. 1

Stages of Gingivitis and Periodontal Disease. Gingivitis typically precedes the various stages of periodontal disease. However, gingivitis does not always progress to periodontal disease. Periodontal disease is irreversible, and the vascular destruction in the oral cavity by pathogenic bacteria correlates with the amount of systemic vascular damage throughout the body (33).

Fig. 2

A Description of the Driver-Passenger Model of the Oral Cavity. The gingiva of those who have periodontal disease are intrinsically colonized by pathogenic bacteria of the red complex or “drivers” of the disease process. These drivers can cause inflammation and increased cell proliferation. This leads to bleeding and rupturing of the tissue, which alters the microenvironment and the selective pressure on the local microbiota. These changes facilitate the gradual replacement of driver bacteria by “passengers,” consisting of opportunistic pathogens or other bacteria with a competitive advantage in the disease process. Progression of the disease may be either suppressed (by healthy passenger bacteria) or promoted (by pathogenic passenger bacteria) because of these microbial colonization changes.

Fig. 3

Hypothetical Diagram of Action of Periodontal Infection in the Induction of Colitis. As a first step, infection with periodontal pathogens led to increased pro-inflammatory cytokines and periodontal infection. When PD is left untreated, the oral pathogens migrate to various parts of the body and colonize locally. Alternatively, either directly or indirectly by modulating gut microbiome, these pathogens can cause reduced tetrahydrobiopterin (BH₄, a cofactor for nitric oxide synthesis) in the large intestine. Reduced BH₄ biosynthesis will lead to uncoupling of nitric oxide synthase decreased NO synthesis, suppression of NRF2-Phase II expression, colon dysmotility and colitis.