Effectiveness of probiotics in irritable bowel syndrome: Updated systematic review with meta-analysis

Table 1 Jadad quality score of randomized controlled trial included in the meta-analysis

Study	Randomization	Blinding	Withdrawals and dropouts	Total score
Kajander et al[33]	2	2	1	5
Williams et al[32]	1	2	1	4
Zeng et al[39]	1	2	1	4
Enck et al[35]	1	1	1	3
Drouault-Holowacz et al[37]	2	2	1	5
Sinn et al[42]	2	2	1	5
Enck et al[36]	1	2	1	4
Simrén et al[40]	2	2	1	5
Sondergaard et al[43]	2	2	1	5
Guglielmetti et al[44]	2	2	1	5
Ducrotté et al[45]	1	2	1	4
Kruis et al[34]	2	2	1	5
Ki cha et al[38]	2	2	1	5
Dapoigny et al[46]	1	2	1	4
Roberts et al[41]	2	2	1	5

Table 2 Characteristics of studies included in the meta-analysis

Trial	Type of IBS	Criteria	Age (yr)		Sex (Male/Female)		Probiotic	Probiotic dosage	Duration of treatment	Follow-up	Outcome
			Probiotic	Placebo	Probiotic	Placebo
Kajander et al[33]	All types	Rome II	50	46	2/41	4/39	Lactobacillusrhamnosus GG	1 × 107 CFU	20 wk	3 wk	↑ Stabilization of intestinal microbiota
							L. rhamnosus Lc705				↓ Distension and abdominal pain in probiotic group
							Propionibacteriumfreudenreichiissp. shermanii JS				↓ IBS symptoms
							Bifidobacteriumanimalisssp. lactis Bb-12
Williams et al[32]	All types	Rome II	40	38	3/25	8/20	L. acidophilus CUL60	2.5 × 1010 CFU	8 wk	2 wk	↑ QoL
							L. acidophilus CUL21				↓ Symptom severity, bloating not improved
							B. lactis CUL34,
							B. bifidum CUL20
Zeng et al[39]	D-IBS	Rome II	44.6	45.8	10/4	9/6	Streptococcusthermophilus	1 × 108 CFU	4 wk	-	Mucosal barrier function and bowel symptoms improved
							L. bulgaricus	1 × 107 CFU			↓ Small bowel permeability
							L. acidophilus
							B. longum
Enck et al[35]	All types	ICHPPC and WONCA	49.8	49.4	76/72	75/75	Escherichia coli (Symbioflor 2)	1.5-4.5 ×107 CFU	8 wk	ND	↓ Typical symptoms of IBS patients
Drouault-Holowacz et al[37]	All types	Rome II	47	44	8/40	16/36	B. longum LA101	1 × 1010 CFU	4 wk	-	↑ QoL
							L. acidophilus LA102				↓ Flatulence
							Lactococcusl actis LA103				↓ Abdominal pain and bloating
							S. thermophilus LA104
Sinn et al[42]	All types	Rome III	41.9	47.5	6/14	8/12	L. acidophilus SDC 2012, 2013	2 × 109 CFU	4 wk	-	↓ IBS symptoms, abdominal pain and discomfort
Enck et al[36]	All types	ICHPPC and WONCA	49.8	49.4	77/72	73/75	E. coli and Enterococcusfaecalis (Pro Symbioflor)	3-9 × 107 CFU	8 wk	-	↓ 50% global symptom score and abdominal pain score
Simrén et al[40]	All types	Rome II	42	44	11/26	11/26	L. paracasei F19	5 × 107 CFU	8 wk	8 wk	Improvement in both groups in pain frequency, pain and bloating severity, satisfaction with bowel habits, and interference with daily life
							L. acidophilus La5
							B. lactis Bb-12
Sondergaard et al[43]	ND	Rome II	53.9	48.5	7/20	6/19	L. paracasei F19	5 × 107 CFU	8 wk	8 wk	Symptom relief in both groups;no difference between probiotics and placebo
							L. acidophilus La5	(500 mL)
							B. lactis Bb-12
Guglielmetti et al[44]	All types	Rome III	36.65	40.98	21/41	19/41	B. bifidum MIMBb75	1 × 109 CFU	4 wk	4 wk	↓ IBS symptoms like: pain, discomfort distension, bloating, digestive disorders
											↑ QoL
Ducrotté et al[45]	D-IBS (in majority of patients)	Rome III	36.53	38.4	70/38	81/25	L. plantarum 299v	1 × 1010 CFU	4 wk	3 wk	↓ Abdominal pain and bloating
Kruis et al[34]	D-IBS	Rome II	46.3	45.1	12/48	16/44	E. coli (Nissle 1917)	2.5-25 × 109 CFU	12 wk	-	No significant effects of probiotics in general symptoms, but enteric flora altered due to gastroenterocolitis or administration of antibiotics before IBS initiation
Ki Cha et al[38]	D-IBS	Rome III	37.9	40.3	12/13	14/11	L. acidophilus	1 × 1010 CFU	8 wk	2 wk	↑ QoL
							L. plantarum
							L. rhamnosus
							B. breve
							B. lactis
							B. longum
							S. thermophilus
Dapoigny et al[46]	All types	Rome III	46.1	48.8	5/20	10/15	L. caseirhamnosus (LCR 35)	6 × 108 CFU	4 wk	2 wk	↓ IBS patients complaining of diarrhea
								(250 mg)			↓ 50% reduction in IBS severity score in probiotic arm
Roberts et al[41]	C-IBS, A-IBS	Rome III	44.66	43.71	14/74	14/77	B. lactis CNCMI-2494	1.25 × 1010 CFU	12 wk	-	Significant improvement in IBS symptoms in both groups

A-IBS: Alternating irritable bowel syndrome; CFU: Colony forming unit; IBS: Irritable bowel syndrome; C-IBS: Constipation-predominant irritable bowel syndrome; D-IBS: Diarrhea-predominant irritable bowel syndrome; ICHPPC: International classification of health problems in primary care; ND: Not determined; QOL: Quality of life; WONCA: World organization of family doctors.

Table 3 Characteristics of studies included in the systematic review

Trial	Type of IBS	Criteria	Age (yr)		Sex (Male/Female)		Probiotic	Probiotic dosage	Duration of treatment	Follow-up	Outcome
			Probiotic	Placebo	Probiotic	Placebo
Agrawal et al[51]	C-IBS	Rome III	39.6		0/19	0/19	Bifidobacteriumlactis DN-173010	1.25 × 1010 CFU	4 wk	1 wk	↓ Abdominal distension and bloating
Hun[48]	D-IBS	Rome II	48.36		9/41		Bacillusc oagulans GBI-306086	8× 108 CFU	8 wk	-	↓ Bloating and abdominal pain
Dolin[67]	D-IBS	Rome III	52.3	44	7/19	6/23	B. coagulans GBI-306086	2 × 109 CFU	8wk	2 wk	↓ Number of daily bowel movements
Guandalini et al[47]	Alltypes	Rome II	4-18		31/28		VSL#3	4.5 × 1011 bacteria	6 wk	6 wk after 2-wk wash-out	↓ Percentage of symptoms, severity and frequency of abdominal pain and bloating
											↑ QoL
Ligaarden et al[53]	All types	Rome II	46.5 (18-75)		5/11		Lactobacillusplantarum MF1298	1 × 1010 CFU	3 wk	-	Daily symptom scores not different between probiotic and placebo groups
Francavilla et al[50]	ND	Rome II	6.5	6.3	43/24	35/23	L. rhamnosus GG	3 × 109 CFU	12wk	8 wk	↓ Frequency and severity of pain, and improved intestinal permeability
Hong et al[49]	All types	Rome III	33	33	12/25	10/26	Lactobacillus sp. HY7801	4 × 109 CFU	8 wk	-	↑ Intestinal barrier function in females
							B. longum HY804				↓ Pain and flatulence defection
							L. brevis HY7401
Choi et al[54]	D-IBS, A-IBS	Rome II	40.2	40.6	18/17	19/20	Saccharomycesboulardii	2 × 1011 CFU	4 wk	-	↑ QoL
Michail et al[52]	D-IBS	Rome III	21.8±17		5/10	3/6	VSL#3	9 × 1011 bacteria	8 wk	-	↑ QoL
											No change in gut microbiota
											↑ Specific GSRS-IBS scores

A-IBS: Alternating irritable bowel syndrome; CFU: Colony Forming Unit; C-IBS: Constipation-predominant irritable bowel syndrome; D-IBS: Diarrhea-predominant irritable bowel syndrome; GSRS: Gastrointestinal Symptom Rating Scale; IBS: Irritable bowel syndrome; ND: Not determined; VSL#3: A probiotic combination of L. casei, L.plantarum, L. acidophilus, L. delbrueckii ssp. bulgaricus, B. longum, B. breve, B. infantis, and S. thermophiles; QoL: Quality of life.

Table 4 Numbers and causes of reported withdrawals in the included clinical trials in the meta-analysis

Study	Group (n)	Cause of withdrawal
		Adverse effect	Non-compliance	Lack of efficacy	Symptom worsening
Drouault-Holowacz et al[37]	Placebo (53)	NR	1	NR	NR
	Probiotic (53)	NR	5	NR	NR
Kajander et al[33]	Placebo (43)	2	NR	NR	NR
	Probiotic (43)	2	NR	NR	NR
Kruis et al[34]	Placebo (60)	NR	NR	2	NR
	Probiotic (60)	2	NR	NR	NR
Enck et al[35]	Placebo (148)	NR	1	1	NR
	Probiotic (149)	2	NR	NR	NR
Enck et al[36]	Placebo (150)	2	NR	NR	NR
	Probiotic (148)	3	NR	NR	NR
Dapoigny et al[46]	Placebo (26)	NR	NR	NR	3
	Probiotic (26)	NR	NR	NR	NR
Ki Cha et al[38]	Placebo (25)	NR	NR	NR	2
	Probiotic (25)	NR	NR	NR	NR

NR: Not reported.