Acquisition of Oral Microbes and Associated Systemic Responses of Newborn Nonhuman Primates

Abstract

The acquisition and development of the complex oral microbiome remain ill defined. While selected species of oral bacteria have been examined in relation to their initial colonization in neonates, a more detailed understanding of the dynamics of the microbiome has been developed only in adults. The current investigation used a nonhuman primate model to document the kinetics of colonization of the oral cavities of newborns and infants by a range of oral commensals and pathogens. Differences in colonization were evaluated in newborns from mothers who were maintained on an oral hygiene regimen pre-and postparturition with those displaying naturally acquired gingivitis/periodontitis. The results demonstrate distinct profiles of acquisition of selected oral bacteria, with the transmission of targeted pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, being passed on primarily from mothers with gingivitis/periodontitis. This colonization resulted in defined patterns of systemic antibody responses in the infants. The significant relative risk measures for infection with the pathogens, as well as the relationship of oral infection and blood serum antibody levels, were consistent with those of the newborns from mothers with gingivitis/periodontitis. These findings indicate that the early acquisition of potentially pathogenic oral bacterial species might impact the development of mucosal responses in the gingiva and may provide an enhanced risk for the development of periodontitis later in life.

Colonization and Persistence of Labeled and “Foreign” Strains of Aggregatibacter actinomycetemcomitans Inoculated into the Mouths of Rhesus Monkeys

“…Our assumptions related to A. actinomycetemcomitans in the mouths of primates is supported by early work by Taichman and colleagues, Beighton et al and Kilian and Rolla and a number of studies by Ebersole and associates all indicating that A. actinomycetemcomitans is routinely present in the mouths of old world primates [11,12,17,18]. As such, implanting a labeled strain of A. actinomycetemcomitans into the mouth of an animal that supports its growth, survival and response to key virulence factors (i.e.…”

“…Furthermore bone loss is the end stage of disease [10]. Moreover, there is little doubt that the primates provide a more accurate model of colonization and disease when compared to rodents [11]. For example, A. actinmycetemcomitans adhesins and leukotoxin have been shown to demonstrate similar levels of specificity with respect to human and primate tissue as compared to rodent tissue [12,13].…”

Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates across the Life Span

“…However, to more fully examine the microbiome changes that occur with disease initiation and progression, only nonhuman primates provide a "microbiomic" analogy to humans. Historically, we and others have documented characteristics of a targeted oral microbiota in primates with periodontal health and changes that occur in periodontitis (53,57,58). Nevertheless, rather minimal data are available documenting the breadth and depth of the oral microbiome in these animal species, although a recent report by Ocon et al (25) clearly demonstrates the component similarity and genomic correspondence of the microbiomes between humans and macaque monkeys.…”

Immune system transcriptome in gingival tissues of young nonhuman primates

“…However, we still have little understanding of how the acquisition of the oral microbiome contributes to the development and maturation of the immune response repertoire in gingival tissues (49). Knowledge of this process will potentially help to clarify the early tissue alterations that could translate into longer-term risk for disease, as well as focusing efforts on approaches to effectively modulate the microbial acquisition by children to improve long term oral health.…”

“…These findings suggest that novel gene patterns could provide some guidance regarding the apparent 'resistance' of the periodontium in the young in response to a microbial challenge, eliciting an inflammatory response but lacking progression to destructive periodontitis, even in the presence of this clinical/molecular gingival inflammation. However, we still have little understanding of how the acquisition of the oral microbiome contributes to the development and maturation of the immune-response repertoire in gingival tissues (49). Knowledge of this process will potentially help to clarify the early tissue alterations that could translate into longer-term risk for disease, as well as focusing efforts on approaches to effectively modulate microbial acquisition by children to improve long-term oral health.…”