Table 3.

Gut bacteria associated with pharmacodynamic effects of drugs

Drug	Animal/human	In vivo/in vitro	Organism or phyla	Effect on PD	Comments
Anti-PD-1 therapy [74]	Both	In vivo	Faecalibacterium and Ruminococcaceae	↑ Systemic and anti-tumor immunity	Enriched gut microbiome increased antigen presentation and improved effector T-cell function in the periphery and the tumor environment
Ipilimumab [75]	Both	In vivo	B. fragilis and/or B. thetaiotaomicron and Burkholderiales	↓ Tumor size	Antitumor effects of the CTLA-4 monoclonal antibody, ipilimumab depend on Bacteroides spp.
Irinotecan [27, 76]	Both	In vitro	B. uniformis and Escherichia coli	↑ GI toxicity	Variability of GI toxicity by anti-cancer drug, irinotecan, is a result of differences in types and levels of gut bacterial β-glucuronidases
NSAIDs [77, 78]	Both	In vivo	β-Glucoronidases	Enteropathy	Various gut microbes have β-glucuronidases that de-glucuronidate NSAIDs in the intestine causing increased susceptibility for enteropathy
Metformin [79, 80]	Both	In vivo	E. coli Intestinibacter	Regulation of glucose homeostasis	Metformin-treated microbiota transferred to germ-free mice improved glucose metabolism
Methotrexate [81]	Human	In vivo	Higher Firmicutes/Bacteroidetes ratio in patients with RA who were non-responsive to methotrexate	Response to methotrexate in patients with RA	Methotrexate-responsive patients had lower microbial diversity; methotrexate responders vs non-responders differed significantly in microbial gene abundance reflecting different microbial pathways

CTLA-4 cytotoxic lymphocyte antigen 4, GI gastrointestinal, NSAID non-steroidal anti-inflammatory drug, PD pharmacodynamics, PD-1 programmed cell death receptor, RA rheumatoid arthritis, ↑ increased, ↓ decreased