late colonizer in ecological succession of the oral microbial biofilm that lands on the top layer of already formed biofilms (Zijnge et al., 2010).
Health as a Homeostatic Relationship Between Commensal Bacteria and Their Host
Initially, Darveau hypothesized that P. gingivalis produces a potent inflammation-inducing lipopolysaccharide (LPS). However, as described in Al-Qutub et al. (2006), he and his research team found that P. gingivalis produces a very complex LPS, one with a lot of structural heterogeneity and specific structural alterations that actually result in reduced inflammation under certain conditions (e.g., hemin concentration can influence LPS structure). So contrary to initial suspicion, Darveau said that P. gingivalis LPS “is very weak at activating inflammation.” In some cases, it actually inhibits TLR-4-mediated inflammation (Coats et al., 2005, 2007). Other researchers have confirmed Darveau’s findings, showing in a similar fashion that P. gingivalis is not only not a strong inducer of inflammation, but also an excellent modulator of host inflammatory response (Darveau, 2010; Hajishengallis et al., 2011).
Refutation of his initial hypothesis led Darveau to propose a new hypothesis: that P. gingivalis is a keystone species in the oral microbiota and that it impacts the host immune system not directly, but by subverting innate immunity in a way that prevents the host from detecting and clearing not just P. gingivalis but other oral microbes as well (Darveau, 2009, 2010). For example, by inhibiting TLR-4-mediated inflammation, P. gingivalis might be inhibiting the ability of TLR-4 to sense not only its own presence (and clear P. gingivalis) but also the presence of other microbes. Darveau noted that P. gingivalis can disrupt host tissue homeostasis via other mechanisms as well, for example, by inhibiting host cell secretion of the chemokine IL-8 in response to other oral microbes, not just in response to P. gingivalis (Darveau et al., 1998). Keystone species do not need to be present in large numbers, Darveau said, in order to exert global effects on the community.
To test the concept of P. gingivalis as a keystone species, Darveau and colleagues colonized both wild-type and germ-free mice with P. gingivalis and detected alveolar bone loss and an increase in total oral bacterial load in the wild-type but not the germ-free mice after 6 weeks (Hajishengallis et al., 2011). The results suggest that commensals must be present in order to induce a diseased state. Wondering if commensals alone could cause bone loss, Hajishengallis et al. (2011) also co-caged germ-free with wild-type mice (i.e., uninfected with P. gingivalis) and measured bone loss after 16 weeks. They reported that, yes, the germ-free mice showed bone loss after 16 weeks of having been co-caged with wild-type mice. Thus, naturally