Table 2.

Clinical studies assessing intestinal microbiota changes during systemic cancer therapy by longitudinal sampling.

Study Design						Main Findings
Study	Type of Cancer	n	Type of Therapy	Sampling Time Points	Method Used for Microbiota Analysis	Effects of Therapy on Microbiota
Chemotherapy
Galloway-Peña et al. (2017), [21]	AML	n = 35	Induction chemotherapy	Baseline: before or within first 24h of chemotherapy; Follow-up: every 96h until neutrophil recovery	16S rRNA gene sequencing	↑ intra-patient temporal variability of α-diversity (CV of Shannon) ↑ Staphylococcus ↑ Streptococcus ↑ Akkermansia ↑ Subdilogranulum ↑ Pseudobutyrivibrio
Sze et al. (2017), [34]	CRC	n = 26	12 surgery 9 surgery + chemotherapy 5 surgery + chemotherapy + radiation	Before and after treatment	16S rRNA gene sequencing	Change in community structure Shift towards healthy microbiota
Galloway-Peña et al. (2016), [20]	AML	n = 34	Induction chemotherapy	Baseline: before therapy; Follow-up: every 96 h until neutrophil recovery	16S rRNA gene sequencing	↑ Lactobacillus ↓ α-diversity (Shannon index) ↓ Blautia
Rajagopala et al. (2016), [15]	ALL	n = 28	Chemotherapy	(1) Before therapy, (2) during induction chemotherapy (3) during consolidation chemotherapy (4) during maintenance chemotherapy	16S rRNA gene sequencing	↑ α-diversity (Shannon index)
Montassier et al. (2015), [33]	Non-Hodgkin’s lymphoma	n = 28	Chemotherapy	Baseline: before chemotherapy; Follow-up: 7 days later	16S rRNA gene sequencing	↑ Proteobacteria ↑ Citrobacter ↑ Klebsiella ↑ Enterococcus ↑ Megasphaera ↑ Parabacreroides ↓ α-diversity (Faith’s phylogenetic diversity, observed species) ↓ Firmicutes ↓ Actinobacteria ↓ Ruminococcus ↓ Oscillospira ↓ Blautia ↓ Lachnospira ↓ Roseburia ↓ Dorea ↓ Coprococcus ↓ Anaerostipes ↓ Clostridium ↓ Collinsella ↓ Adlercreutzia ↓ Bifidobacterium
Montassier et al. (2014), [6]	Non-Hodgkin’s lymphoma	n = 8	Chemotherapy	Baseline: before chemotherapy; Follow-up: 1 week after chemotherapy	16S rRNA gene pyrosequencing/dHPLC	↑ Bacteroidetes ↑ Proteobacteria ↑ Bacteroides ↑ Escherichia ↓ α-diversity (OTUs, Chao index, Shannon index) ↓ Firmicutes ↓ Actinobacteria ↓ Blautia ↓ Faecalibacterium ↓ Roseburia ↓ Bifidobacterium
Stringer et al. (2013), [37]	Breast cancer, gastrointestinal cancer	n = 10	Chemotherapy (FOLFOX4, FOLFOX6, FOLFIRI, capecitabine)	(1) Before chemotherapy (2) Day 2 of chemotherapy (3) Day 5 (4) Day 10	Bacterial growth tests with selective media, real-time PCR	↑ E.coli ↑ Lactobacillus spp. (until day 5, then decrease)
Dörffel et al. (2012), [31]	NET	n = 13	Chemotherapy	Before and during therapy	FISH	↑ Faecalibacterium prausnitzii (midgut NET only)
Zwielehner et al. (2011), [32]	Different types of cancer	n = 17	Chemotherapy	(1) Before chemotherapy (2) Day 1–4 after chemotherapy (5) Day 5–9 after chemotherapy	qPCR/PCR-DGGE	↓ Bacteroides ↓ Bifidobacteria ↓ Clostridium cluster IV ↓ Clostridium cluster XIVa
		n = 2	Chemotherapy	(1) Before chemotherapy (2) Day 1–4 after chemotherapy	High throughput sequencing	↑ Enterococcus faecium ↑ Clostridium difficile ↑ Peptostreptococcaceae ↓ Faecalibacterium prausnitzii ↓ Lactobacilli ↓ Veillonella spp. ↓ Bifidobacteria ↓ E.coli/Shigella
Wada et al. (2010), [38]	Different types of cancer	n = 23	Chemotherapy	(1) Before chemotherapy (2) Within 24 h after initiation (3) Once weekly	Bacterial cultures (n = 3)	↑ Enterobacteriaceae
Van Vliet et al. (2009), [39]	Pediatric AML	n = 9	Chemotherapy	(1) Day 2 of chemotherapy (2) Day 11 of chemotherapy (3) ≥6 weeks after treatment	PCR-DGGE	↓ α-diversity
Immunotherapy
Routy et al. (2018), [26]	NSCLC (n = 15) RCC (n = 17)	n = 32	Anti-PD-1	(1) Before treatment (2) After 2nd injection (1 month) (3) After 4th injection (2 months) (4) After 12th injection (6 months	Metagenomic shotgun sequencing	↑ α-diversity (Richness) ↑ Candidatus Alistipes marseilloanorexicus ↑ Clostridium scindens ↑ Eubacterium sp. ↑ Clostridium sp. ↑ Streptococcus salivarius ↑ Clostridiales ↑ Eubacterium eligens
Chaput et al. (2017), [27]	Metastatic melanoma with colitis	n = 7	Ipilimumab	At baseline and at the time of colitis occurrence	16S rRNA gene sequencing	↓ α-diversity (Shannon index) ↓ Ruminococcus ↓ Lachnospiracea incertae sedis ↓ Blautia ↓ Clostridium IV ↓ Eubacterium ↓ unclassified Lachnospiraceae ↓ Pseudoflavonifracto ↓ Butyrate producing bacterium L2-21 ↓ Ruminococcus bromii ↓ Blautia obeum 1-33 ↓ Eubacterium coprostanoligenes HL ↓ Clostridium clostridioforme LCR24 ↓ Alistipes spe 627 ↓ Blautia obeum ↓ Butyrate producing bacterium PH08AY04 ↓ Clostridium leptum DSM 753T ↓ Bacterium ASF500 ↓ Clostridium sp JC3 ↓ Rumen bacterium 2-293-25 ↓ Bacterium ic ↓ Butyrate producing bacterium M21-2 ↓ Unidentified bacterium CCCM23 ↓ Unidentified bacterium CCCM41 ↓ Ruminococcus bromii L2-63 ↓ Clostridiales bacterium JN18-V41
Vetizou et al. (2015), [41]	Metastatic melanoma	n = 18	Ipilimumab	See Chaput et al. (2017)	16S rRNA gene sequencing	↑ Bacteroides salyersiae ↑ Bacteroides acidifaciens ↑ Bacteroides uniformis ↓ Prevotella copri ↓ Bacteroides sp. ↓ Barnesiella intestinohominis ↓ Parabacteroides distasonis
Dörffel et al. (2012), [31]	Midgut NET	n = 11	Interferon alpha-2b	Before and during therapy	FISH	↑ Faecalibacterium prausnitzii

↑: Increase, ↓:Decrease, AML: acute myeloid leukemia; CRC: colorectal cancer; ALL: acute lymphoblastic leukemia; dHPLC: denaturing high-performance liquid chromatography; NET: neuroendocrine tumor; PCR-DGGE: polymerase chain reaction denaturing gradient gel electrophoresis; RCC: renal cell carcinoma; NSCLC: non-small cell lung cancer,; FISH: fluorescent in situ hybridization.