TABLE 1

Comparison of methods for studying drug-microbiome interactions

MethodRelevanceStrengthsLimitations
Culture collection screensADMEIdentifies culturable active isolatesFront-ended effort for collection curation
Ex vivo fecal incubationsADMELarge genetic diversity sampledInterstrain antagonism and culture bias
Fecalase preparationsMCulture independentRequirement for cofactors may mask metabolism
RNA-seq (microbial)MMay identify single effectors/pathwaysInduction may not occur for all effectors
Comparative genomicsADMEYields information on evolution  and distributionLarge number of isolates needed
Functional genomicsMDirectly identifies genesChoice of platform (host and vector) may  influence expression/success
Gene knockout library (microbial)MSystematically identifies candidate genesGenetic tools not available for most gut bacteria
Microbiota profilingMIdentifies drug-responsive microbesDrug may not be stimulatory or inhibitory to metabolizer
Cell culture transport modelsADEWell established and high throughputImmunoregulation may not be represented
Gnotobiotic modelsADEIsolates in vivo effect of specific microbesDifferences in regulation/metabolism between host species
Antibiotic knockdown modelsADEEasier and cheaper than gnotobioticsKnockdown incomplete/unstable; reproducibility
RNA-seq (host)ADEIdentifies pathways of modulationEffects could be post-transcriptional
  • A, absorption; D, distribution; M, metabolism; E, excretion; RNA-seq, RNA sequencing.