Table 1.

Hill's criteria of causality applied to periodontitis^*.

	Questions	Examples of Questions Specific to Periodontitis
Biological Plausibility	Does a hypothesized effect make sense in the context of current biological knowledge?	Can dysbiosis (microbial shift) be associated with chronic human disease?
Dose Response
Natural	Does disease occur more in individuals closer to the source?	Are higher levels of pathogenic bacteria associated with periodontitis?
Interventional	Does disease recede with antimicrobial treatment?	Does therapy reduce the number of suspected agents and improve the oral health of the patient?
Strength of Association	What is the risk of disease after infection?	Do most patients who have these pathogens develop periodontitis? Are most patients with periodontitis colonized with the same bacterial pathogens (e.g., “red complex” bacteria)?
Specificity of Association	Is the agent associated with only one clinical syndrome?	Do “red complex” bacteria cause diseases other than periodontitis?
Consistency	Do studies by different groups consistently arrive at the same findings?	Do most laboratories agree upon which bacterial species are associated with periodontitis?
Temporality	Does infection precede disease?	Does infection with the suspected pathogens precede development of periodontitis? Can these pathogens induce periodontitis in animal models?

^*Table adapted from Lowe et al. (43).