Table 1 Molecular guidelines for establishing microbial causation of disease

Putative pathogen genome is present in most cases of disease

Microbial nucleic acid should be found preferentially in diseased sites in combination with anatomic, histologic, chemical or clinical evidence of pathology and not in areas lacking the pathology

Only diseased tissue should harbor putative pathogen genome

Fewer, or no, copy numbers of pathogen-associated nucleic acid sequences should occur in non-diseased host or tissue

Disease resolution should be accompanied by a reduction in copy number of pathogen genome

Disease resolution perhaps due to effective clinical treatment should lead to undetectable or reduced pathogen-associated nucleic acid. Any relapse in disease should see an increase in copy number

Microbial sequence may be detected before disease or may correlate with disease severity

A causal relationship can be more strongly inferred when pathogen-associated nucleic acid is present before disease onset and copy number correlates with disease severity

The nature of the microbial organism associated by detection of its nucleic acid should be consistent with known biological characteristics of that group of organisms

When phenotypes such as pathology, microbial morphology and clinical features are predicted by sequence-based phylogeny the meaningfulness of the detected sequence can be enhanced

Microbe-associated sequences detected in disease tissue should be corroborated at the cellular level

In situ hybridization of microbial sequences in an area of tissue pathology (or where microorganisms are thought to be located) should be attempted

Molecular evidence should be reproducible

Any sequence-based evidence for microbial causation must be replicated