Fecal microbiota transplantation for the treatment of irritable bowel syndrome: A systematic review and meta-analysis

Table 1 Characteristics of randomised controlled trials of faecal microbiota transplantation for treating irritable bowel syndrome

Ref.	Trial design	Country	Sample size	IBS subtypes	Inclusion criteria	Frequency and route of administration	FMT-content	Placebo content	Pretreatment	Number of donors
Aroniadis et al[59], 2019	RCT, crossover	United States	48 (25 FMT vs 23 placebo)	IBS-D	Moderate-to-severe IBS symptoms (IBS-SSS > 175)	3 d of 25 oral capsules	3 × 25 frozen capsules (0.38 g donor stool/capsule) (Openbiome)	Non-toxic brown pigment	PPI for three days	One donor for one patient (four different donors)
El-Salhy et al[60], 2020	RCT, 3 parallel groups	Norway	164 (54/30 gram FMT, 55/60 gram FMT, 55 placebo)	All subtypes	Moderate-to-severe IBS symptoms (IBS-SSS > 175)	Single treatment via gastroscope to distal duodenum	Once 30 g or 60 gram of frozen feces in sterile saline solution	Autologous faeces	None	One donor
Halkjær et al[43], 2018	RCT, 2 parallel groups	Denmark	51 (25 FMT, 26 placebo)	All subtypes	Moderate-to-severe IBS symptoms (IBS-SSS > 175)	12 d of 25 oral capsules	25 FMT capsules (one daily dose containing approximately 12 g frozen faecal material)	Saline, glycerol and food colouring E150	Bowel cleansing	Donor mix from four donors
Holster et al[61], 2019	RCT, 2 parallel groups	Sweden	16 (8 FMT, 8 placebo)	All subtypes	IBS with small amounts of butyrate-producing bacteria	Single treatment via colonoscopy to the caecum	30 g frozen stool in sterile saline and glycerol	Autologous feces	Bowel cleansing and 4 mg loperamide	Two donors (three patients received stool from donor 1, the remaining five from donor 2)
Holvoet et al[44], 2021	RCT, 2 parallel groups	Belgium	62 (43 FMT, 19 placebo)	IBS-D and IBS-M	Refractory IBS with failure of at least three conventional IBS therapies	Single treatment via nasojejunal administration	Fresh feces mixed with saline	Autologous feces	Bowel cleansing	Two donors
Johnsen et al[62], 2018	RCT, 3 parallel groups	Norway	83 (26 fresh FMT, 29 frozen FMT, 28 placebo)	IBS-D and IBS-M	Moderate-to-severe IBS symptoms (IBS-SSS > 175)	Single treatment administered into the caecum via colonoscopy	50–80 g fresh or frozen feces mixed with saline and glycerol	Autologous feces	Bowel cleansing and 8 mg loperamid	Donor mix from two donors
Lahtinen et al[58], 2020	RCT, 2 parallel groups	Finland	51 (25 FMT, 26 placebo)	IBS-D, IBS-M and IBS-U	Patients who remained symptomatic despite receiving conventional treatment	Single treatment administered into the caecum via colonoscopy	30 g frozen suspension	Autologous feces	Bowel cleansing	One donor
Singh et al[63], 2022	RCT, 4 parallel groups	United States	23 (11 FMT, 12 placebo)	IBS-D	IBS-SSS > 150 or > 175	Single treatment with 19 oral capsules	Capsule contain 0.75 frozen fecal filtrate) (Openbiome)	Glycerol with brown coloring agent	Bowel cleansing	Six donors (unknown if donors were mixed)

FMT: Fecal microbiota transplantation; IBS: Irritable bowel syndrome; IBS-C: Constipation-predominant irritable bowel syndrome; IBS-D: Diarrhoea-predominant irritable bowel syndrome; IBS-M: Mixed irritable bowel syndrome; IBS-U: Unclassified irritable bowel syndrome; RCT: Randomised controlled trials; PPI: Proton pump inhibitors.

Table 2 Summarised findings for comparing fecal microbiota transplantation with placebo for the treatment of irritable bowel syndrome

Outcomes and timeframe	Anticipated absolute effects		Relative effect (95%CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
	Effect in placebo	Effect difference with FMT (95%CI)
Improvement of symptoms after three months	42 per 100	8 or more per 100 (from 13 or fewer to 46 or more)	RR 1.19 (0.68-2.10)	484 (8 RCTs)	++--1 Low	Improvement of symptoms as measured by a validated global IBS symptoms score (e.g., IBS-SSS scale from 0, no symptoms, to 500, maximum symptoms) (as defined by each trial)
Improvement of symptoms after six months	38 per 100	5 or fewer per 100 (from 25 or fewer to 52 or more)	RR 0.88 (0.33-2.39)	99 (3 RCTs)	++--2 Low	Improvement of symptoms as measured by a validated global IBS symptoms score (e.g., IBS-SSS scale from 0, no symptoms, to 500, maximum symptoms) (as defined by each trial)
Adverse events prior to end of trial	26 per 100	4 or more per 100 (from 10 or fewer to 30 or more)	RR 1.17 (0.63-2.15)	450 (7 RCTs)	++--3 Low	Common adverse events were mild and self-limiting gastrointestinal symptoms
Serious adverse events prior to end of trial	1 per 100	1 or fewer per 100 (from 1 or fewer to 2 or more)	RR 0.42 (0.07-2.60)	501 (8 RCTs)	++--4 Low	Serious adverse events included one suicide (placebo), cholecystitis (placebo), and one admission to the hospital due to discomfort after the FMT procedure
Dropouts due to adverse events prior to end of trial	1 per 100	1 or fewer per 100 (from 1 or fewer to 1 or more)	RR 0.24 (0.03-2.17)	502 (8 RCTs)	++--5 Low	Dropouts due to adverse events include one suicide (placebo) and one for discomfort after the FMT procedure (placebo)
Improvement in QoL scores after three months	NA	NA	MD -6.30 (-13.39 to 0.79)	406 (7 RCTs)	++--6 Low	Improvement of quality of life as measured by a validated scale IBS-QoL, where 34 items are summed and averaged for a total score and then transformed to a 0-100 scale for interpretation (high scores indicate better IBS-QoL)

¹Downgraded two levels due to considerable inconsistency (I² = 82%) and imprecision (267 events).

²Downgraded two levels due to moderate inconsistency (I² = 51%) and serious imprecision (34 events).

³Downgraded two levels due to substantial inconsistency (I² = 69%) and imprecision (142 events).

⁴Downgraded two levels due to serious imprecision (three events) and wide confidence interval.

⁵Downgraded two levels due to serious imprecision (two events) and wide confidence interval.

⁶Downgraded two levels due to moderate inconsistency (I² = 45%), heterogeneous method, and a small number of participants.

Patients or population: Participants diagnosed with irritable bowel syndrome according to a physician’s opinion or an accepted, symptom-based diagnostic criteria. Settings: Inpatient and outpatient. Intervention: Fecal microbiota transplantation. Comparison: Placebo (or autologous feces). FMT: Fecal microbiota transplantation; IBS: Irritable bowel syndrome; SSS: Symptom severity score; QOL: Quality of life measure; MD: mean difference; NA: Not available; RR: Risk ratio.