Probiotic supplementation decreases intestinal transit time: Meta-analysis of randomized controlled trials

Table 1 Study characteristics

Ref.	Study design	Active: control (n:n)	Transit timeoutcome, method	Probiotic strain	Daily dosage(109 cfu)	Delivery method	Treatmentduration (d)
Agrawal et al[14]	Parallel groups	17:17	CTT, radiopaque markers	B. lactis DN-173 010	25.0	Active: Yogurt + probioticControl: Nonfermented milk-based product	28
Bartram et al[15]	Cross-over	12	OATT, radiopaque markers	B. longum	> 0.5	Active: Yogurt with 2.5 g lactulose + probioticControl: Yogurt	21
Bouvier et al[16]	Parallel groups	36:36	CTT, radiopaque markers	B. lactis DN-173 010	97.5	Active: Probiotic fermented milkControl: Heat-treated probiotic fermented milk	11
Holma et al[17]	Parallel groups	12:10	TITT, radiopaque markers	L. rhamnosus GG	20	Active: Buttermilk + probiotic and white wheat breadControl: White wheat bread	21
Hongisto et al[18]	Parallel groups	16:14	TITT, radiopaque markers	L. rhamnosus GG	15	Active: Yogurt + probiotic and low fiber toastControl: Low fiber toast	21
Malpeli et al[19]	Cross-over	83	OCTT, carmine red dye	B. lactis BB12L. casei CRL 431	2-20 2-12	Active: Yogurt with 0.625 g inulin and oligofructose + probioticControl: Yogurt	15
Marteau et al[20]	Cross-over	32	CTT, radiopaque markers	B. lactis DN-173 010	18.75	Active: Yogurt + probioticControl: Yogurt	10
Rosenfeldt et al[21]	Cross-over	13	GTT, radiopaque markers	L. rhamnosus 19070-2,L. reuteri DSM 12246	20 20	Active: Freeze-dried powder + probioticControl: Skimmed milk powder w/dextrose	18
Rosenfeldt et al[21]	Cross-over	13	GTT, radiopaque markers	L. casei subsp. alactus CHCC 3137,L. delbrueckii subsp. lactis CHCC 2329,L. rhamnosus GG	20 20 20	Active: Freeze-dried powder + probioticControl: Skimmed milk powder w/dextrose	18
Sairanen et al[22]	Parallel groups	22:20	CTT, radiopaque markers	B. longum BB536, B. lactis 420,L. acidophilus 145	2.4-181 0.48	Active: Probiotic fermented milkControl: Fermented milk	21
Waller et al[23]	Parallel groups	33:34	WGTT; radiopaque markers	B. lactis HN019	1.8	Active: Capsule, maltodextrin, probioticControl: Capsule, maltodextrin	14
Waller et al[23]	Parallel groups	33:34	WGTT; radiopaque markers	B. lactis HN019	17.2	Active: Capsule, maltodextrin, probioticControl: Capsule, maltodextrin	14
Krammer et al[24]	Parallel groups	12:12	CTT, radiopaque markers	L. casei Shirota	6.5	Active: Probiotic fermented milk drinkControl: Nonfermented milk drink	28

¹Represents the reported range of total Bifidobacterium spp. cfu: Colony-forming units; CTT: Colonic transit time; GTT: Gastrointestinal transit time; OATT: Oro-anal transit time; OCTT: Oro-cecal transit time; TITT: Total intestinal transit time; WGTT: Whole gut transit time. L. rhamnosus: Lactobacillus rhamnosus; B. lactis: Bifidobacterium lactis; L. casei: Lactobacillus casei.

Table 2 Subject characteristics

Ref.	Age (yr)	Female gender	BMI (kg/m2)	Condition
Agrawal et al[14]	40	100%	25	IBS-C
Bartram et al[15]	23	58%	-	None
Bouvier et al[16]	33	50%	22	None
Holma et al[17]	44	92%1	24	Constipation
Hongisto et al[18]	43	100%	24	Constipation
Malpeli et al[19]	41	100%	-	Constipation
Marteau et al[20]	27	100%	21	None
Rosenfeldt et al[21]	25	0%	-	None
Rosenfeldt et al[21]	25	0%	-	None
Sairanen et al[22]	39	64%	25	None
Waller et al[23]	44	65%	31	Constipation
Waller et al[23]	44	65%	32	Constipation
Krammer et al[24]	50	100%	-	Constipation

¹Percentage estimated from larger study cohort. BMI: Body mass index; IBS-C: Irritable bowel syndrome, constipation predominant; “-“: Represents missing data.

Table 3 Assessment of study quality

Ref.	Jadad scale
	Randomization(range: 0-2)	Double blinding(range: 0-2)	Subject account(range: 0-1)	Total score1(range: 0-5)
Agrawal et al[14]	1	2	1	4
Bartram et al[15]	1	2	0	3
Bouvier et al[16]	1	2	0	3
Holma et al[17]	1	0	1	2
Hongisto et al[18]	1	0	0	1
Malpeli et al[19]	0	2	1	3
Marteau et al[20]	1	2	1	4
Rosenfeldt et al[21]	1	1	0	2
Rosenfeldt et al[21]	1	1	0	2
Sairanen et al[22]	1	1	0	2
Waller et al[23]	2	2	1	5
Waller et al[23]	2	2	1	5
Krammer et al[24]	1	1	1	3

¹Higher scores represent better study quality.

Table 4 Meta-regression of study- and subject-related factors on intestinal transit time

Variable	Unit of measure	Intercept	Point estimate	Explained variance	P-value
Constipation	0 = no, 1 = yes	0.171	0.415	39%	0.01
Age	Per 10 years	-0.445	0.230	27%	0.03
Female gender proportion	Per 10%	0.024	0.053	23%	< 0.05
Body mass index1	Per 5 kg/m2	-0.544	0.200	25%	0.11
Daily probiotic dosage	Per 10 × 109 cfu	0.454	-0.013	1%	0.62
Treatment duration	Per 1 wk	0.535	-0.048	1%	0.67

¹Body mass index not reported for 5 treatment effects.

Table 5 Subgroup analysis of study- and subject-related factors on intestinal transit time

Study	SMD	95%CI	P-value(within groups)	P-value(between groups)
Subject condition
Constipation/IBS-C (n = 7)	0.59	0.39-0.79	< 0.001	0.01
Healthy (n = 6)	0.17	-0.08-0.42	0.18
Age
≥ 40 years (n = 7)	0.59	0.39-0.79	< 0.001	0.01
< 40 years (n = 6)	0.17	-0.08-0.42	0.18
Study design
Parallel groups (n = 8)	0.49	0.24-0.75	< 0.001	0.23
Cross-over (n = 5)	0.25	-0.06-0.56	0.11
Body mass index1
≥ 25 kg/m2 (n = 4)	0.61	0.27-0.95	< 0.001	0.29
< 25 kg/m2 (n = 4)	0.34	-0.02-0.70	0.06
Female gender proportion
≥ 75% (n = 6)	0.44	0.17-0.76	< 0.01	0.47
< 75% (n = 7)	0.32	0.05-0.60	0.02
Treatment duration
< 20 d (n = 7)	0.43	0.18-0.67	< 0.001	0.62
≥ 20 d (n = 6)	0.32	-0.02-0.66	0.07
Daily probiotic dosage
≥ 1010 cfu (n = 8)	0.41	0.14-0.68	< 0.01	0.84
< 1010 cfu (n = 5)	0.36	0.05-0.68	0.02

¹Body mass index not reported for 5 treatment effects. IBS-C: Irritable bowel syndrome, constipation predominant; SMD: Standardized mean difference.

Table 6 Subgroup analysis of probiotic strains on intestinal transit time

Probiotic strain	Treatment effects (n)	SMD	95%CI	P-value
B. lactis HN019	2	0.72	0.27-1.18	< 0.01
B. lactis DN-173 010	3	0.54	0.15-0.94	< 0.01
L. rhamnosus GG	2	0.25	-0.38-0.87	0.44
Other single strains	2	0.23	-0.41-0.87	0.48
Strain combinations	4	0.17	-0.18-0.52	0.34

SMD: Standardized mean difference. B. lactis: Bifidobacterium lactis; L. rhamnosus: Lactobacillus rhamnosus.

Table 7 Sample size requirements for randomized controlled trials based on standardized mean difference

SMD	Study design
	Parallel groups1	Cross-over
0.2	786	156
0.3	350	71
0.4	198	41
0.5	128	27
0.6	90	19
0.7	66	15
0.8	52	12

¹Total sample size, assuming 1:1 active-to-control group ratio. Assumes two-sided alpha of 0.05 and statistical power of 80%. Attrition estimate not included. SMD: Standardized mean difference.