It is fairly settled that periodontal disease, inflammation of the gums, increases the risk of developing cardiovascular disease, among other conditions. Chronic inflammation drives faster progression of all of the common age-related diseases, and gum disease is a potent source of inflammation. To pick one example from the many supporting research results, you might look to a recent study that demonstrated reduced markers of chronic inflammation achieved through nothing more than better dental hygiene. People better equipped to remove dental plaque on a daily basis exhibited reduced inflammation as a result, and that reduced inflammation will translate to a modestly lower risk and severity of a range of age-related conditions. If you dig further in the Fight Aging! archives, you'll find all sorts of unpleasant correlations involving gum disease, such as with the amyloid deposits associated with Alzheimer's disease, and with cognitive decline in general. Thus taking greater care of your teeth and gums is just a really good idea on many fronts.
An open access paper I noticed today adds more evidence to the existing body of work on this topic. Without looking at inflammation in any depth, the researchers found that specific forms of bacteria found in the mouth are associated with an elevated risk of death. Dental plaque and gum disease of course originates in the unwanted activities of bacteria resident in the mouth, but there are many different species involved. As pointed out by the researchers, it is the interactions between these species that seem as important as the presence of one or another: specific combinations appear to produce the worst outcomes, not just one type of bacteria. This is interesting research when considered in the broader context, as there is considerable enthusiasm in the dental research community in finding ways to get rid of specific bacterial species from the mouth, such as those that cause cavities, or those that build plaque and inflame the gums. This is a challenging task, unfortunately: removing bacteria from the mouth is one thing, but doing so selectively and then keeping the unwanted species from quickly returning is quite another. This is a technological capability yet to be developed into a useful and reliable form, but the benefits of achieving this goal will clearly extend far beyond the health of teeth.
Mucosal surfaces, including the oral mucosa, are colonized by a complex and dynamic microbial ecosystem called "microbiota" that has important implications for human health and disease. While more epidemiological evidence is warranted, periodontal microbiota has been identified as a causative agent of periodontitis, which is one of the most prevalent diseases in human population. Interestingly, some animal and human observational evidence supports that periodontitis is not just an oral, in situ disease. The disease also contributes to several systemic diseases including diabetes and cardiovascular diseases (CVD). The chronic inflammatory processes of periodontitis are considered to be responsible for the etiologies. In the oral cavity, the inflammatory and immunologic reactions following periodontitis induce the production of pro-inflammatory cytokines resulting in the breakdown of periodontal epithelium and connective tissues. Systematically, the chronic trickling of periodontal microbiota into the bloodstream elicits a systemic inflammation response resulting in elevated levels of various inflammatory mediators and cross-reactive systemic antibodies, which promote risk for many systemic diseases. Importantly, it has been shown that the increased periodontitis-related all-cause and CVD mortalities are comparable with, but independent of, diabetes-related mortality.
It is believed that complex interactions between specific periodontal pathogens and different bacterial combinations are more relevant to periodontitis than are individual species. We therefore hypothesize that a similar phenomenon exists in the association between periodontal microbiota and mortality rates. To test our hypothesis, we related 21 serum immunoglobulins G (IgGs) against periodontal bacteria to the rates of all-cause, diabetes-related, and hypertension-related mortalities in a death cohort from a representative sample of the US population, the Third National Health and Nutrition Examination Survey (NHANES III). In this study, we found that two baseline serum IgG patterns, Factor 1 and Factor 2, were significantly associated with higher all-cause and/or diabetes-related mortality rates among people without history of diabetes, CVD, and cancers. While only Factor 2 was related to all-cause mortality, both Factor 1 and Factor 2 were related to diabetes-related mortality. To our best knowledge, this is the first data showing that specific oral microbiota may have an impact on the rate of death in humans.
Serum IgGs reflected human systemic response to the corresponding periodontal bacteria and studies have shown that individual periodontal bacterial quantities were significantly correlated with corresponding serum antibody levels. Therefore, the serum IgG levels can be considered as host-related phenotypes of periodontal microbiota. Our analysis showed that, although the two mortality-related IgG patterns that we characterized featured several bacteria, which were also featured in periodontitis-related complexes, they were in different combinations. It seemed that different bacterial combinations have different impacts on human health. Interestingly, our findings coincide with the hypothesis of Porphyromonas gingivali (PG) as a keystone pathogen. It is conceived that the mere presence of a keystone pathogen, even at very low colonization levels, can modulate host response in ways that alter the amount and composition of subgingival microbiota, thereby triggering adverse effects on human health. It has been demonstrated in a periodontal model that the introduction of PG, even at low numbers, in cooperation with other dysbiotic bacteria led to a marked acceleration in pathological alveolar bone loss, but PG alone failed to induce periodontitis. Importantly, our findings from Factor 1 and Factor 2 also, respectively, suggested that active periodontitis may increase diabetes-related death rate, and that, even without clinically significant periodontitis, the presence of PG at very low colonization levels increase total and diabetes-related death rate. It seemed that the elimination of PG is crucial in reducing risk for both periodontitis and mortality.
Our findings collaborated with previous observations that periodontitis, a result of polymicrobial infection, increased the risk for several major diseases, such as diabetes, CVD, cancers, and mortalities as well. The etiologies may involve several pathological consequences leading to uncontrolled inflammation, such as elevated levels of systemic proinflammatory cytokines, oxidative stress, formation of advanced glycation end products, disturbed microbe-host nutrition and metabolism interaction, etc. These mechanisms may be responsible not only for the initiation but also for the promotion and progression of the diseases as well, and thus lead to higher death rates. However, it has been shown that periodontal microbial interactions are complex and that numerous genes related to motility, metabolism, and virulence in one bacterium are differentially regulated in the presence of others. The detailed mechanisms relating specific combinations of periodontal bacteria to specific diseases or death rates warrant further study. The information would be valuable in developing personalized therapeutic and prevention strategies.