Horizontal and Vertical Transfer of Oral Microbial Dysbiosis and Periodontal Disease

Abstract

One of the hallmark features of destructive periodontal disease, well documented over the last 50 y, is a change to the quantitative and qualitative composition of the associated microbiology. These alterations are now generally viewed as transformational shifts of the microbial populations associated with health leading to the emergence of bacterial species, which are only present in low abundance in health and a proportionate decrease in the abundance of others. The role of this dysbiosis of the health associated microbiota in the development of disease remains controversial: is this altered microbiology the driving agent of disease or merely a consequence of the altered environmental conditions that invariably accompany destructive disease? In this work, we aimed to address this controversy through controlled transmission experiments in the mouse in which a dysbiotic oral microbiome was transferred either horizontally or vertically into healthy recipient mice. The results of these murine studies demonstrate conclusively that natural transfer of the dysbiotic oral microbiome from a periodontally diseased individual into a healthy individual will lead to establishment of the dysbiotic community in the recipient and concomitant transmission of the disease phenotype. The inherent resilience of the dysbiotic microbial community structure in diseased animals was further demonstrated by analysis of the effects of antibiotic therapy on periodontally diseased mice. Although antibiotic treatment led to a reversal of dysbiosis of the oral microbiome, in terms of both microbial load and community structure, dysbiosis of the microbiome was reestablished following cessation of therapy. Collectively, these data suggest that an oral dysbiotic microbial community structure is stable to transfer and can act in a similar manner to a conventional transmissible infectious disease agent with concomitant effects on pathology. These findings have implications to our understanding of the role of microbial dysbiosis in the development and progression of human periodontal disease.

Biogenesis of Type V pili

“…Among periodontopathic bacteria, Porphyromonas gingivalis , Tannerella forsythia , and Treponema denticola are strongly associated with the onset and progression of chronic periodontitis and are referred to as the “red complex.” 8 In particular, P. gingivalis is a keystone pathogen because even a small population of this pathogen can initiate and exacerbate chronic periodontitis 9 . Recently, a dysbiotic microbial community formed as a result of P. gingivalis infection was reported to mediate periodontitis in a mouse model 10 …”

“…9 Recently, a dysbiotic microbial community formed as a result of P. gingivalis infection was reported to mediate periodontitis in a mouse model. 10 As P. gingivalis is unable to use carbohydrates as an energy source, the bacterium secretes proteases with significant proteolytic ability to use peptides per amino acids as an energy source, such as gingipains, and various peptidases, including dipeptidyl peptidases, to survive in the periodontal pocket where there is deeper space around teeth caused by periodontal disease. Gingipains consist of arginine-specific proteases (RgpA and RgpB) and a lysine-specific protease (Kgp).…”

A 16S rRNA Gene and Draft Genome Database for the Murine Oral Bacterial Community

“…Despite this inherent simplicity of the mouse oral microbiome, it has significant relevance as a model to investigate and understand the mechanisms of human oral diseases such as periodontitis (7,9,10). A primary reason for this has been the parallels observed in the nature of the initiation and development of disease in experimental studies, specifically the development of a dysbiotic microbiome (characterized by increased total microbial loads) and soft tissue destruction with gingival inflammation (2,11,12), which are often comparable to that seen among humans (13,14). Also, since the microbial genera observed are often similar to the predominant ones seen in humans (15), these animal models are also useful for understanding host-microbiota interactions and homeostasis mechanisms in health and disease.…”

Oral dysbiosis induced by Porphyromonas gingivalis is strain-dependent in mice

“…Due to an insertion element, W83 is disrupted for the mfaI gene, while TDC60 produces Mfa1 type I [ 24 ]. This could be an advantage for colonizing the oral cavity of mice, as its indigenous microbiome is frequently dominated by Streptococcus [ 33 , 34 ]. RagA and RagB are outer membrane receptor linked to transporter TonB, and an associated lipoprotein, respectively.…”