Table 1.

Studies addressing the relationship between drugs commonly used in pediatric patients and gut microbiota. ↑, increased; ↓, decreased.

Drug Name	Year	First Author	Setting	Sample Size	Interaction with Gut Microbiome	Ref
Irinotecan (CPT-11)	2015	Wallace, BD	Preclinical	/	Intestine bacteria producing β-glucuronidase can convert non-toxic CPT-11 metabolite (SN-38-G) to toxic metabolite (SN-38), causing diarrhea.	[23]
Irinotecan (CPT-11)	2008	Stringer, AM	Preclinical, rats	/	↑ number of β-glucuronidases-expressing species.	[24]
Cyclophosphamide	2013	Viaud, S	Preclinical	/	Translocation of specific Gram-positive bacteria from the intestine to secondary lymphoid organs was critical for the differentiation of CD4+ T cells into Th1 and Th17 cells.	[25]
Cyclophosphamide	2015	Xu, X	Preclinical	/	↑ Firmicutes, ↓ Bacteroidetes.	[26]
L-asparaginase	2021	Dunn, KA	Pediatric ALL	12 patients	↑ Escherichia in the community if decreased-activity, ↑ Bacteroides and Streptococcus in the community if increased-activity.	[27]
Anti-PD1	2018	Gopalakrishnan, V	Adults, melanoma	112 patients	↑ α-diversity of responders to anti-PD1 therapy. Higher proportion of Ruminococcaceae, Faecalibacterium, and Bifidobacterium spp. reported in responders.	[28]
Anti-PD1	2018	Routy, B	Mice, Adults	Mice, 249 treated	↑ Akkermansia, Ruminococcus spp., Alistipes spp., and Eubacterium spp in responders. ↓ Bifidobacterium adolescentis, B. longum, and Parabacteroids distasonis in responders.	[29]
Cyclosporine	2019	Jia et al.	Preclinical	8 treated	↑ gut microbial richness, Enterobacteriaceae. ↓ F. prausnitzii, Clostridium clusters I and XIV.	[30]
Cyclosporine	2020	O Reilly et al.	Adults	6 ex vivo, 8 in vivo	No significant α and β diversity before and after treatment.	[31]
Tacrolimus	2017	Zhang et al.	Mice	8 treated	No change in bacterial richness and diversity. ↑ genera Allobaculum, Bacteroides and Lactobacillus. ↓ Clostridiales, Ruminococcaceae, Rikenella, Ruminococcaceae and Oscillospira.	[32]
Tacrolimus	2017	Bhat et al.	Mice	5 treated	↓ Mollicutes, Micrococcaceae, Actinomycetales, Roseburia, Oscillospira, Rothia and Staphylococcus. ↑ A. muciniphila.	[33]
Tacrolimus	2018	Toral et al.	Mice	8 treated	↓ microbial diversity. ↑ Firmicutes/Bacteroidetes ratio.	[34]
Tacrolimus	2018	Jiang et al.	Mice	8 high dosage, 8 medium dosage, 8 low dosage	Intermediate dose: ↑ Bifidobacterium, Faecalibacterium prausnitzii ↓ less Enterobacteriaceae, Bacteroides-Prevotella Low and high doses: ↑ Enterobacteriaceae ↓ Bifidobacterium, Faecalibacterium prausnitzii.	[35]
MMF	2018	Flannigan et al.	Mice	9 treated	↓ overall diversity ↑ Proteobacteria (Escherichia/Shigella), Deferribacteres, Firmicutes ↓ Bacteroidetes and Verrucomicrobia phyla, Akkermansia, Parabacteroides and Clostridium genera.	[36]
Rapamycin	2017	Bhat et al.,	Mice	5 treated	↓ bacterial diversity. ↓ Roseburia, Oscillospira, Mollicutes, Rothia, Micrococcaceae, Acninomycetales and Staphylococcus.	[33]
Rapamycin	2016	Jung et al.	Mice	5 treated	↓ Turicibacter, unclassified Marinilabiliaceae, Alloprevotella. ↑ Ruminococcus.	[37]
Alemtuzumab	2013	Li et al.	Monkeys	15 treated	↑ Enterobacteriales order and Prevotella genus. ↓ Lactobacillales order.	[38]
Steroids	2014	Lee et al.	Humans	4 treated	↓ Clostridiales ↑ Erysipelotrichales.	[39]
Steroids	2016	Tourret et al.	Mice	8–10 treated	↑ Firmicutes/Bacteroidetes ratio ↓ Clostridium sensu stricto.	[40]
Steroids	2017	Wu et al.	Mice	30 lower dose, 30 higher dose	↓ bacterial richness and diversity. ↓ Firmicutes, Bacteroides, Actinobacteria, α and γ Proteobacteria, Clostridiales and Lactobacillus. ↑ Proteobacteria.	[41]
Steroids	2019	He et al.	Mice	10 treated	↓ Proteobacteria, Deferribacteres, Rikenella, Mucispirillum, Oscillospira and Bilophila. ↑ Prevotella and Anaerostipes.	[42]
Steroids	2020	Vich Vila et al.	Adults	17 treated	↑ Methanobrevibacter smithii and Streptococcus salivarius.	[43]
PPI	2016	Jackson et al.	Adults	1827	↓ diversity in PPI users. ↑ Lactobacillales order, families Micrococcaceae and Streptococcaceae, genera Rothia and Streptococcus, species Rothia mucilaginosa and Streptococcus anginosus. ↓ families Erysipelotrichaceae, Lachnospiraceae, Ruminococcaceae, genera Firmicutes, species Erysipelotrichales and Clostridiales.	[44]
PPI	2015	Imhann et al.	Adults	99 treated	↓ species richness and ↓ Shannon diversity, although not significant. ↑ Gammaproteobacteria class, Actinomycetales order, families Streptococcaceae and Micrococcaceae, genera Rothia, Streptococcus and Veilonella, species Lactobacillus salivarius.	[45]
PPI	2015	Freedberg et al.	Adults	12 treated	No changes in diversity. ↑ families Enterococcaceae, Streptococcaceae, Micrococcaceae and Staphylococcaceae. ↓ Clostridiales.	[46]
PPI	2015	Tsuda et al.	Adults	18 treated	No changes in α diversity, increased β diversity. ↓ genus Faecalibacterium.	[47]
PPI	2020	Vich Vila et al.	Adults	108 treated	↑ species Veillonella parvula, Streptococcus salivarius, Streptococcus parasanguinis, Streptococcus vestibularis, Bifidobacterium dentium, Haemophilus parainfluenzae.	[43]
PPI	2021	Simakachorn et al.	Pediatrics	20 treated	No significant change in α and β diversity. No change in total number of species-level taxonomy categories.	[48]
UDCA	2018	Pearson et al.	Adults	661 treated	No change in microbial richness. ↑ Streptocuccus, Escherichia and Bilophila spp., Faecalibacterium prausnitzii; ↓ Fusobacterium spp., Ruminococcus gnavus.	[20]
UDCA	2018	Tang et al.	Adults	60 treated	↑ Enterobacteriaceae.	[49]