Increasing evidence incriminates low-grade inflammation in cardiovascular, metabolic diseases,
and neuropsychiatric clinical conditions, all important causes of morbidity and mortality. One of
the upstream and modifiable precipitants and perpetrators of inflammation is chronic periodontitis, a
polymicrobial infection with Porphyromonas gingivalis (P. gingivalis) playing a central role in the disease
pathogenesis. We review the association between P. gingivalis and cardiovascular, metabolic, and
neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation
as well as downregulation induced by the pathogen. In addition to inflammation, translocation of the
pathogens to the coronary and peripheral arteries, including brain vasculature, and gut and liver vasculature
has important pathophysiological consequences. Distant effects via translocation rely on virulence
factors of P. gingivalis such as gingipains, on its synergistic interactions with other pathogens, and on its
capability to manipulate the immune system via several mechanisms, including its capacity to induce
production of immune-downregulating micro-RNAs. Possible targets for intervention and drug development
to manage distal consequences of infection with P. gingivalis are also reviewed.