Systematic review of randomised controlled trials: Probiotics for functional constipation

Table 1 Characteristics of included trials

Study ID	Probiotic	Design	Allocation concealment/Blinding/Intention-to-treat analysis/Description of withdrawals or dropouts	Exp/cont (age, yr)	Definition of constipation	Duration of intervention	Intervention (daily dose)	Placebo
Studies in adults
Mollenbrink et al[13] 1994 (Germany)	E. coli Nissle 1917	RCT, crossover	Unclear/Yes/No/Yes	35/35 (18-60)	< 2 BM per week	4 + 4 wk	25 × 109 CFU	Placebo
Koebnick et al[12] 2003 (Germany)	L. casei Shirota	RCT, parallel	Unclear/Yes/Yes/Yes	35/35 (18-70)	Not provided	4 wk	6.5 × 109 CFU, probiotic beverage	Placebo
Yang et al[14] 2008 (China)	B. lactis DN-173 010	RCT, parallel	Unclear/No/Yes/Yes	63/63 (25-65, only women)	< 3 BM per week; increased stool hardness; non-organic constipation and habitual constipation	2 wk	Fermented milk containing 1.25 × 1010 CFU of probiotic plus yoghurt strains	Placebo (acidified milk without any ferments or probiotics)
Studies in children
Banaszkiewicz et al[17] 2005 (Poland)	L. rhamnosus GG	RCT, parallel (computer-generated randomisation list)	Yes/Yes/Yes/Yes	43/41 (2-16)	< 3 BM per week during 14 days for at least 12 wk	12 wk	Lactulose plus LGG 2 × 109 CFU	Lactulose plus placebo
Bu et al[16] 2007 (Taiwan)	L. casei rhamnosus Lcr35	RCT, parallel (computer-generated randomisation list)	Yes/Yes/Yes/Yes	18/9 (< 10)	< 3 BM per week for > 2 mo plus at least one of the criteria: anal fissures with bleeding due to constipation, faecal soiling, or passage of large and hard stool	4 wk	8 × 108 CFU	Placebo (starch)

RCT: Randomised controlled trials; CFU: Colony-forming units; BM: Bowel movements.

Table 2 The summary of study outcomes

Study ID	Probiotic	Outcomes
Studies in adults
Mollenbrink et al[13] 1994 (Germany)	E. coli Nissle 19171	Number of stools per week [week 4: 4.9 ± 1.5 vs 2.6 ± 1.0, MD 2.3 (95% CI 1.7 to 2.9); week 8: MD 4.1 (95% CI 3.2 to 5)]
		Hard stools [2/34 vs 16/30, RR 0.1 (95% CI 0.03 to 0.4) (P < 0.001)]
		Effectiveness of a probiotic compared to placebo assessed by physicians: 55.9% vs 6.7%
		Effectiveness of a probiotic compared to placebo assessed by patients: 52.9% vs 6.7% (P < 0.001)
		Tolerance of a probiotic compared to placebo assessed by physicians: 58.85% vs 26.7% (P = 0.01)
		Tolerance of a probiotic compared to placebo assessed by patients: 50% vs 26.7% (P = 0.03)
Koebnick et al[12] 2003 (Germany)	L. casei Shirota2	Occurrence of moderate and severe constipation (P < 0.001)
		Degree of constipation (P = 0.003)
		Defecation frequency (P = 0.004)
		Occurrence of hard stools (P < 0.001)
		Degree of stool consistency (P < 0.001)
		Occurrence of flatulence (NS)
		Degree of flatulence (NS)
		Occurrence of bloating (NS)
		Degree of bloating (NS)
Yang et al[14] 2008 (China)	B. lactis DN-173 0101	Stool frequency (n/wk) [week 1: 3.5 ± 1.5 vs 2.5 ± 0.9, MD 1 (95% CI 0.6 to 1.4); week 2: 4.1 ± 1.7 vs 2.6 ± 1.0; MD 1.5 (95% CI 0.7 to 1.6)]
		Defection condition scores [week 1: 1.1 ± 0.9 vs 1.6 ± 1.1, MD -0.5 (95% CI -0.85 to -0.18); week 2: 0.8 ± 1.0 vs 1.6 ± 1.1; MD -0.8 (95% CI -1.14 to -0.44)]
		Grade I (0 points)-normal defecation
		Grade II (1 point)-only bearing down and uncomfortable sensation
		Grade III (2 points)-obvious bearing down and uncomfortable sensation, or frequent defecation with difficult and little defecation, seldom abdominal pain or anal burning sensation
		Grade IV (3 points)-often abdominal pain or anal burning sensation to influence defecation
		Stool consistency scores (according to classification method of Bristol) [week 1: 1.0 ± 0.8 vs 1.4 ± 1.0, MD -0.4 (95% CI -0.73 to -0.12); week 2: 0.6 ± 0.8 vs 1.3 ± 1.0, MD -0.7 (95% CI -1 to -0.4)]
		Grade I (0 points)-like sausage or snake, smooth and soft; like sausage, with fissure on the surface
		Grade II (1 point)-sausage-shaped, with lumps; noncohesive lumps, with coarse edges
		Grade III (2 points)-separating hard lumps, like fruit kernel (difficult discharge)
Studies in children
Banaszkiewicz et al[17] 2005 (Poland)	L. rhamnosus GG2	Treatment success (≥ 3 spontaneous BMs per week with no episodes of faecal soiling) (NS)
		Number of BMs per week (NS)
		Number of episodes of faecal soling per week (NS)
		Straining at defecation frequency per week (NS)
Bu et al[16] 2007 (Taiwan)	L. casei rhamnosus Lcr351	Treatment success (≥ 3 spontaneous BMs per week with no episodes of faecal soiling in the fourth week) (14/18 vs 1/9, RR 7, 95% CI 1.1 to 45; P = 0.01)
		Defecation frequency (times/d) (0.57 ± 0.17 vs 0.37 ± 0.1; MD 0.2, 95% CI 0.1 to 0.3)(P = 0.03)
		Hard stool (%) (22.4 ± 14.7 vs 75.5 ± 6.1; MD -53% (95% CI -63 to -43) ((P = 0.01)
		Abdominal pain (times) (1.9 ± 1.6 vs 6.7 ± 3.3; MD -4.8, 95% CI -6.6 to -3) (P = 0.03)
		Use of glycerin enema (times) (1.6 ± 1.9 vs 4.0 ± 2.1; MD -2.4, 95% CI -4 to -0.8) (P = 0.04)
		Use of lactulose (times) (4.4 ± 3.6 vs 6.2 ± 3.8; MD -1.8, 95% CI -4.7 to 1.1) (P = 0.66)
		Faecal soiling (times) (2.1 ± 3.8 vs 2.7 ± 1.4, MD -0.6 (95% CI -3.2 to 2) (P = 0.95)
		Change of appetite (0.7 ± 0.8 vs 0.7 ± 0.6; MD 0, 95% CI -0.6 to 0.6) (P = 0.81)

¹Mean values are presented for the experimental group and control group, respectively;

²Comparisons of experimental and control group. NS: Not significant.