Inflammatory Networks Linking Oral Microbiome with Systemic Health and Disease

Abstract

The dance between microbes and the immune system takes place in all biological systems, including the human body, but this interaction is especially complex in the primary gateway to the body: the oral cavity. Recent advances in technology have enabled deep sequencing and analysis of members and signals of these communities. In a healthy state, the oral microbiome is composed of commensals, and their genes and phenotypes may be selected by the immune system to survive in symbiosis. These highly regulated signals are modulated by a network of microbial and host metabolites. However, in a diseased state, host-microbial networks lead to dysbiosis and considerable burden to the host prior to systemic impact that extends beyond the oral compartment. Interestingly, we presented data demonstrating similarities between human and mice immune dysbiosis and discussed how this affects the host response to similar pathobionts. The host and microbial signatures of a number of disease states are currently being examined to identify potential correlations. How the oral microbiome interacts with inflammation and the immune system to cause disease remains an area of active research. In this review, we summarize recent advancements in understanding the role of oral microbiota in mediating inflammation and altering systemic health and disease. In line with these findings, it is possible that existing conditions may be resolved by targeting specific immune-microbial markers in a positive way.

Keywords: cytokines; dysbiosis; inflammation; interactome; resolution; systems biology.

Figure 1.

Dysbiotic inflammation is present in human and murine cytokine levels in disease (type 2 diabetes [T2D]). Original cytokine data are displayed to exemplify dysbiosis in the immune response, placing the host at risk of more aggressive microbial behavior. Mean levels (pg/mL) of 13 cytokines in mice (right side of circle, n = 5 healthy, n = 5 diabetic) and humans (left side of circle, n = 5 healthy, n = 5 diabetic). Health, green; type 2 diabetes, orange. Data show similar trends between human and mice cytokine levels, with higher expression among diseased versus healthy subjects. Radar lines mark 25 pg/mL; black bars show standard deviation.

Figure 2.

The oral microbiome interacts with host inflammatory networks, with oral dysbiosis inducing local disease. Schematic diagram of oral microbiome inflammatory interactions in health (left panel) and disease (right panel). In a healthy state, the oral microbiome and host immune system exist in a state of symbiosis, with commensal bacteria and sentinel host immune cells (neutrophils, inflammasomes) coexisting in oral tissue. This symbiosis is characterized by a diverse oral microbiome, with any inflammation (due to injury or insult) being acute and actively resolved to restore tissue integrity and homeostasis. However, should microbial dysbiosis occur, there is an enrichment of pathogenic over commensal bacteria and increased immune cell infiltration (neutrophils, macrophages, dendritic cells, other lymphocytes) in oral tissue, which can lead to biofilm and subsequent inflammasome formation. This failure to recognize or control bacterial dysbiosis, with immune cell infiltration, causes chronic low-grade inflammation, which can lead to tissue loss locally and systemic disease more broadly. Image created with BioRender.com.

Figure 3.

Dynamic interactions of the oral microbiome and host inflammatory networks play a role in oral dysbiosis and the oral impact on systemic diseases. The oral microbiome plays a key role in health and systemic disease. In a healthy state, homeostatic interactions of systemic and oral tissues lead to health. These driving factors affect systemic health through the oral-metabolism, oral-vascular, oral-brain, oral-gut, oral-development, and oral-blood axes. In contrast, oral dysbiosis can act through these axes to activate pathologic inflammatory networks, leading to chronic inflammation and, in conjunction with environmental factors, affecting systemic organs and aggravating systemic diseases, including diabetes, cardiovascular diseases, autoimmune diseases, age-related ailments, lung diseases, cancers, osteoporosis, pregnancy complications, and neurodegenerative diseases. Image created with BioRender.com. CVD, cardiovascular disease; IBD, inflammatory bowel disease.