Table 3.

Randomized controlled trials investigating the effect of fecal microbiota transplantation on gut microbiota and microbiota metabolites.

Authors, Years	Diagnostic Criteria, Study Duration	Sample Size, IBS Subtypes	Allocation	Donors	Bowel Cleansing	FMT Route and Location (Upper/Lower GI Tract), Frequency	Dosage of FMT Group	Dosage of Control Group	Microbial Analysis	Findings
Aroniadis et al., 2019 [93]	Rome III, 3 months	n = 48: 100% IBS-D	1:1	Four donors, not mixed	No	Oral capsule ( upper), multiple lasted 3 days	25 frozen capsules (0.38 g FMT) per day	25 placebo capsules per day	16S rRNA	Bacterial composition of FMT recipients shifted closer to that of the donors.
El-salhy et al., 2019 [91]	Rome IV, 3 months	n = 165: 37.8% IBS-C; 38.4% IBS-D; 23.8% IBS-M	1:1:1	One donor, not mixed	No	Gastroscopy (upper), single FMT	Frozen 30 g FMT and 60 g FMT	Frozen 30 g autologous feces	16S rRNA	Higher abundance of Eubacterium biforme, Lactobacillus spp. and Alistipes spp., lower abundance of Bacteroides spp. Inverse correlation between IBS symptoms and the concentrations of Lactobacillus spp. and Alistipes spp. Negative correlation between the Fatigue Assessment Scale score and the concentration of Alistipes spp.
Halkjær et al., 2018 [94]	Rome III, 6 months	n = 52: 33.3% IBS-C; 29.4% IBS-D; 37.3% IBS-M	1:1	Four donors, mixed FMT	Yes	Oral capsule (upper), multiple administrations lasted 12 days	25 frozen capsules (50 g FMT)	25 placebo capsules per day	16S rRNA	Fecal donors had higher biodiversity than IBS patients. Microbiota of FMT recipients are more similar to the donors’ microbiota than to that of the placebo recipient. Microbiota of placebo recipient did not become more similar to the donors’ microbiota than patients with IBS before randomization. Bacteroides genus and Ruminococcaceae family correlate positively with IBS symptoms score. Blautia genus and Clostridiales correlate negatively with IBS symptoms score.
Holster et al., 2019 [90]	Rome III, 6 months	n = 17: 25% IBS-C; 56.3% IBS-D; 18.8% IBS-M	1:1	Two donors, not mixed	Yes	Colonoscopy (lower), single FMT	Frozen 30 g FMT	Frozen 30 g autologous feces	Human Intestinal Tract Chip (fecal and mucosa)	The abundance of butyrate-producing bacteria in patients’ fecal samples was not lower than the donors at baseline. Microbial composition of patients had changed to resemble that of the donor after FMT. No effect on microbial diversity was observed after FMT in fecal or mucosal microbiota.
Holvoet et al., 2020 [89]	Rome III, 3 months	n = 62: 100% IBS-D/IBS-M.	2:1	Two donors; not mixed	No	Naso-jejunal tube (upper), single FMT	Donor fresh feces	Autologous feces	16S rRNA	Donors’ fecal samples had higher diversity than the patients. Responders to FMT had a higher microbial diversity at baseline compared to non-responders. There was a significant difference in overall bacterial composition between responder and non-responders before treatment. Bacterial composition of FMT recipients shifted closer to that of the donors.
Johnsen et al., 2018 [92]	Rome III, 12 months	n = 90: 53% IBS-D; 47% IBS-M	2:1	Two donors, mixed	Yes	Colonoscopy (lower), single FMT	Frozen or fresh 50–80 g FMT	Frozen or fresh 50– 80 g autologous feces	Not reported	Not reported
Lahtinen et al., 2020 [88]	Rome III, 3 months	n = 55: 51% IBS-D; 14.3% IBS-M; 28.6% IBS unsubtyped; 6.1% other	1:1	One donor, not mixed	Yes	Colonoscopy (lower), single FMT	Frozen 30 g FMT	Fresh 30 g autologous feces	16S rRNA	Changes in gut microbiota profile was observed.

IBS: irritable bowel syndrome; IBS-C: constipation-predominant IBS; IBS-D: diarrhea-predominant IBS; IBS-M: mixed-IBS; FMT: fecal microbiota transplantation; GI: gastrointestinal.