What is the possibility that weight gain is directly the result of a change in oral flora? The results of this study suggest that of the 40 species surveyed, levels of many bacteria differed in the saliva of overweight women when compared with levels in the saliva of healthy individuals. In particular, the percentage of the bacterium S. noxia was capable of identifying 98.4% of overweight women from a group of generally healthy persons, a surprisingly high degree of diagnostic power.
could be considered a disease candidate. Selenomonads, in general, are motile, crescent-shaped, non-spore-forming, Gram-negative bacteria which actively ferment glucose to produce propionic acid, and are obligate anaerobes found in both the mouth and the gastro-intestinal tract. The type strain for S. noxia
(ATCC 43541) was isolated from the gingival crevice of a person with rapidly progressive periodontitis. It was among the species found to increase in experimental gingivitis (Selenomonas
D4) in both children and adults (Moore et al., 1984
). It was one of the candidate species associated with de novo
development of periodontal disease, where the percentage in periodontal plaque increased from 0.9% at healthy sites to 5.9% in disease-active interproximal sites (Tanner et al., 1998
). It has also been reported to be elevated in the mouths of mothers giving birth to pre-term low-birthweight babies (Buduneli et al., 2005
). Although these studies suggest that S. noxia
may be capable of triggering an inflammatory reaction and presumably stimulating release of inflammatory mediators, they do not immediately suggest a link between S. noxia
Several findings indirectly support the hypothesis that oral bacteria could be related to obesity. The most direct evidence for a bacterial association with obesity comes from animal studies (DiBaise et al., 2008
). In these studies, germ-free C57BL_6 mice were shown to eat more but to gain less weight than littermates infected by fecal samples from wild-type mice. Concomitantly, levels of glucose, insulin, and leptin were higher in conventionalized mice (i.e
., germ-free mice exposed to cecal contents of wild-type mice), indicating the development of an insulin-resistant state. These studies demonstrated that gut microbiota promoted absorption of monosaccharides in these mice, which resulted in lipogenesis. Adult mice infected from wild-type mice had 60% more fat than their germ-free counterparts. In subsequent studies, this group demonstrated that bacteria responsible for this effect in mice were in the Firmicutes phylum. It is interesting to note that S. noxia
was the only Firmicutes that was significantly elevated in saliva (, ). Other investigators have shown that this tendency to gain weight in mice is transmissible between mice by coprophagia. Elevated levels of Firmicutes relative to Bacteroidetes were also found in studies of the gene sequences of human gut bacterial species. The authors hypothesized that individuals predisposed to obesity may have gut levels of Firmicutes that promote more efficient extraction and/or storage of energy from a given diet, compared with lean individuals, and that intentional manipulation of gut microbiology may be useful for controlling weight in overweight individuals. The condition of obesity arising from infection has been called “infectobesity”. Although these studies focused on gut bacteria, all gastrointestinal bacteria pass through the oral cavity at some time, and some of those transients might be located in, if not seeded from, the oral cavity. It has been estimated that approximately 1 gram of bacteria (1011
) is swallowed with the 500 to 1500 mL of saliva produced daily (Socransky and Haffajee, 2005
). If the levels of S. noxia
are > 1.05%, this represents approximately 109
cells swallowed each day. It is therefore plausible that salivary microbiology would affect gastrointestinal microbiology. This sentiment is echoed by the great interest in orally administered exogenous bacteria (probiotic therapy).
Possible mechanisms by which oral bacteria could affect body weight and contribute to obesity.
In a completely different context, investigators studying the social interactions between overweight and non-overweight humans (Christakis and Fowler, 2007
) found that obesity appears to spread through social associations. Based on a study of social interactions among 12,607 participants in the Framingham Heart Study, a person’s chances of becoming overweight increased by 57% if he or she had a close friend who became overweight. This was true of siblings and spouses, but not of neighbors. This spread is reminiscent of that described for the periodontal pathogen P. gingivalis,
where spouses and children of individuals with periodontal disease have higher levels of “pathogens” than those who do not have periodontal disease (Socransky and Haffajee, 2005
Two prevalent oral diseases are found in most, if not all, people: dental caries and periodontal disease. Dental caries, the most common oral disease, is clearly related to the consumption of fermentable carbohydrates. Since obesity has also been related to carbohydrate consumption, one would think that dental caries and obesity would correlate strongly. Such is not the case. Most authors have not reported a positive association.
In contrast to dental caries, the association between periodontal disease and obesity is subtle, but widely acknowledged. Both periodontal disease and obesity produce increased levels of inflammatory mediators. In a review of this subject (Ritchie, 2007
), fat was recognized as a reservoir for inflammatory cytokines, and it was suggested that obesity would likely affect periodontal disease. In the context of this paper, however, we would propose the converse by considering the likelihood that periodontal disease may contribute to the development of obesity. Periodontal disease is an inflammatory condition thought to be caused by the “red complex” bacteria P. gingivalis, T. denticola,
and T. forsythia
. By community ordination analysis, S. noxia
was found as an outlier, not commonly associated with any of the periodontal disease complexes. Studies of early periodontal lesions (Tanner et al., 1998
), however, suggested that T. forsythia, C. rectus,
and S. noxia
were principal species associated with sites converting from periodontal health to disease. Periodontitis has also been significantly correlated with overweight conditions. Analysis of data from a national health survey (NHANES III) indicated that BMI and periodontal attachment loss are positively correlated (Wood et al., 2003
). Analysis of populations with and without periodontitis indicate that 70% with periodontitis are overweight or obese, as compared with 37% of the healthy individuals (Socransky and Haffajee, 2005
). In addition, overweight individuals appeared to have more severe periodontal disease, as evaluated by plaque, bleeding on probing, pocket depth, attachment loss, and percentage of subgingival T. forsythia
Tumor necrosis factor-α (TNFα) is one of many pro-inflammatory cytokines produced by diseased periodontal tissues that could be a pivotal inflammatory cytokine encouraging obesity. TNFα increases insulin resistance, induces C-reactive peptide production, and inhibits adiponectin, an important anti-inflammatory adipokine. Increased levels of TNFα in gingival crevice fluid have been shown to correlate with increased body mass index (Lundin et al., 2004
). Treatment of periodontitis with locally administered tetracycline and repeated scaling and root planing reduced blood levels of TNFα (Iwamoto et al., (2001)
In individuals with diabetes, effective periodontal therapy with antibiotics reduced glycated hemoglobin (Janket et al., 2005
). By this mechanism, periodontal bacteria would be seen to stimulate the formation of inflammatory cytokines such as TNFα that divert energy metabolism to lipid synthesis, perhaps contributing to obesity.
Oral bacteria may contribute to the development of obesity by at least 3 mechanisms (). First, the oral bacteria may contribute to increased metabolic efficiency, as suggested by the infectobesity proponents. It is instructive to note that, by this mechanism, even a small excess in calorie consumption, with no change in diet or exercise, might result in unacceptable weight gain. An increase by 5% (100 calories/day) would add approximately 10 pounds of fat per year. A second hypothesis is that oral bacteria could increase weight gain by increasing appetite. Even in the absence of data, the teleology of this proposition is so attractive that it should be mentioned in this context. By stimulating host appetite, the bacteria get more to eat! A third hypothesis is that oral bacteria redirect energy metabolism by facilitating insulin resistance through increasing levels of TNFα or reducing levels of adiponectin.
By any of these mechanisms, even a small excess in calorie consumption with no change in diet or exercise could result in unacceptable weight gain. By the same logic, individuals who are infected may have reduced their caloric intake and/or increased their exercise to compensate and not appear overweight. Hence, any study of infection-related weight gain should include a measure of food consumption and exercise, which was not incorporated into our pilot study. It should also be recognized that an important limitation of the study as conducted is the use of a convenience population as a control, rather than using selected cohorts. This reservation aside, however, rarely have data been reported from saliva in which S. noxia
represented such a large percentage of the oral bacterial population (Mager et al., 2003
). While it is not justified to suggest that S. noxia
infections have an etiologic role in obesity, based on these data, it is reasonable to suggest that S. noxia
may be an indicator of change in oral microbial ecology.
The reasons for a relationship between obesity and oral bacteria are undoubtedly complex and varied. The relationship may be circumstantial, as being related to diet. It could be opportunistic, such as proliferation driven by metabolic changes that have occurred in the host. It could also be causal, as participating in initiation or propagation of the disease. Whatever the reasons, it is clear that the parallel microbiological universe that travels with man changes as man changes, and appears to be affected by a tendency to gain weight.