Contemporary meta-analysis of short-term probiotic consumption on gastrointestinal transit

Table 1 MEDLINE search strategy

Therapeutic search terms

Probiotic

Synbiotic

Lactobacill

Bifidobacteri

Yogurt (yoghurt)

Fermented milk

Main outcome search terms

Gastrointestinal

Transit

Gut

Motility

Colonic

Constipation

Irritable bowel

Combination terms

or/1-6

or/7-13

and/14-15

Table 2 Study characteristics

Study	Country	Study design	n(active: control)	Transit timeoutcome, method	Probiotic strain	Daily dosage(109 CFU)	Delivery method	Treatmentduration(d)
Agrawal et al[14], 2009	United Kingdom	Parallel groups	17:17	CTT, radiopaque markers	B. lactis DN-173 010	25	Active: Yogurt + probiotic	28
							Control: Nonfermented milk-based product
Bartram et al[15], 1994	Germany	Cross-over	12	OATT, radiopaque markers	B. longum	> 0.5	Active: Yogurt with 2.5 g lactulose + probiotic	21
							Control: Yogurt
Bazzocchi et al[25], 2014	Italy	Parallel groups	19:12	TITT, radiopaque markers	L. plantarum, L. acidophilus, L. rhamnosus, B. longum, B. breve	-	Active: Sachet with psyllium+probiotic	56
							Control: Sachet with 2.8 g maltodextrin
Bouvier et al[16], 2001	France	Parallel groups	36:36	CTT, radiopaque markers	B. lactis DN-173 010	97.5	Active: Probiotic fermented milk	11
							Control: Heat-treated probiotic fermented milk
Holma et al[17], 2010	Finland	Parallel groups	12:10	TITT, radiopaque markers	L. rhamnosus GG	20	Active: Buttermilk + probiotic and white wheat bread	21
							Control: White wheat bread
Hongisto et al[18], 2006	Finland	Parallel groups	16:14	TITT, radiopaque markers	L. rhamnosus GG	15	Active: Yogurt + probiotic and low fiber toast	21
							Control: Low fiber toast
Krammer et al[24], 2011	Germany	Parallel groups	12:12	CTT, radiopaque markers	L. casei Shirota	6.5	Active: Probiotic fermented milk drink	28
							Control: Nonfermented milk drink
Magro et al[26], 2014	Brazil	Parallel groups	26:21	CTT, radiopaque markers	L. acidophilus NCFM, B. lactis HN019	2	Active: Yogurt + polydextrose + probiotic Control: Yogurt	14
Malpeli et al[19], 2012	Argentina	Cross-over	83	OCTT, carmine red dye	B. lactis BB12	2-20	Active: Yogurt with 0.625 g inulin and oligofructose + probiotic	15
					L. casei CRL 431	2-12	Control: Yogurt
Marteau et al[20], 2002	France	Cross-over	32	CTT, radiopaque markers	B. lactis DN-173 010	18.75	Active: Yogurt + probiotic	10
							Control: Yogurt
Merenstein et al[27], 2014	United States	Crossover	68	CTT, radiopaque markers	B. animalis ssp. lactis Bf-6	20-56	Active: Yogurt + probiotic	14
							Control: Yogurt
Rosenfeldt et al[21], 2003a	Denmark	Cross-over	13	GTT, radiopaque markers	L. rhamnosus 19070-2	20	Active: Freeze-dried powder + probiotic	18
					L. reuteri DSM 12246	20	Control: Skimmed milk powder w/dextrose
Rosenfeldt et al[21], 2003b	Denmark	Cross-over	13	GTT, radiopaque markers	L. casei subsp. alactus CHCC 3137	20	Active: Freeze-dried powder + probiotic	18
					L. delbrueckii subsp. lactis CHCC 2329	20	Control: Skimmed milk powder w/dextrose
					L. rhamnosus GG	20
Sairanen et al[22], 2007	Finland	Parallel groups	22:20	CTT, radiopaque markers	B. longum BB536, B. lactis 420	2.4-181	Active: Probiotic fermented milk	21
					L. acidophilus 145	0.48	Control: Fermented milk
Tulk et al[28], 2013	Canada	Crossover	65	GTT, carmine red/carbon black capsules	B. lactis Bb12, L. acidophilus La5, L. casei CRL431	2	Active: Yogurt + probiotic + inulin	15
							Control: Yogurt
Waller et al[23], 2011a	United States	Parallel groups	33:34	WGTT; radiopaque markers	B. lactis HN019	1.8	Active: Capsule, maltodextrin, probiotic	14
							Control: Capsule, maltodextrin
Waller et al[23], 2011b	United States	Parallel groups	33:34	WGTT; radiopaque markers	B. lactis HN019	17.2	Active: Capsule, maltodextrin, probiotic	14
							Control: Capsule, maltodextrin

¹Represents the reported range of total Bifidobacterium. CFU: Colony-forming units; CTT: Colonic transit time; GTT: Gastrointestinal transit time; OATT: Oro-anal transit time; OCTT: Oro-cecal TT; TITT: Total intestinal transit time; WGTT: Whole gut transit time.

Table 3 Subject characteristics

Study	Mean age (yr)	Female gender (%)	Mean BMI (kg/m2)	Condition
Agrawal et al[14], 2009	40	100	25	IBS-C
Bartram et al[15], 1994	23	58	-2	None
Bazzocchi et al[25], 2014	40	86	19	Constipation
Bouvier et al[16], 2001	33	50	22	None
Holma et al[17], 2010	44	921	24	Constipation
Hongisto et al[18], 2006	43	100	24	Constipation
Krammer et al[24], 2011	50	100	-2	Constipation
Magro et al[26], 2014	32	91	28	Constipation
Malpeli et al[19], 2012	41	100	-2	Constipation
Marteau et al[20], 2002	27	100	21	None
Merenstein et al[27], 2014	29	100	23	None
Rosenfeldt et al[21], 2003a	25	0	-2	None
Rosenfeldt et al[21], 2003b	25	0	-2	None
Sairanen et al[22], 2007	39	64	25	None
Tulk et al[28], 2013	29	60	24	None
Waller et al[23], 2011a	44	65	31	Constipation
Waller et al[23], 2011b	44	65	32	Constipation

¹Percentage estimated from larger study cohort;

²Represents missing data. BMI: Body mass index; IBS-C: Irritable bowel syndrome, constipation predominant.

Table 4 Assessment of study quality

Study	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], 2009	1	2	1	4
Bartram et al[15], 1994	1	2	0	3
Bazzocchi et al[25], 2014	1	2	1	4
Bouvier et al[16], 2001	1	2	0	3
Holma et al[17], 2010	1	0	1	2
Hongisto et al[18], 2006	1	0	0	1
Krammer et al[24], 2011	1	1	1	3
Magro et al[26], 2014	2	2	1	5
Malpeli et al[19], 2012	0	2	1	3
Marteau et al[20], 2002	1	2	1	4
Merenstein et al[27], 2014	2	2	1	5
Rosenfeldt et al[21], 2003a	1	1	0	2
Rosenfeldt et al[21], 2003b	1	1	0	2
Sairanen et al[22], 2007	1	1	0	2
Tulk et al[28], 2013	1	1	1	3
Waller et al[23], 2011a	2	2	1	5
Waller et al[23], 2011b	2	2	1	5

¹Higher scores represent better study quality.

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

Study	SMD	95%CI	P value	P value
			(pre-post)	(between groups)
Subject condition
Constipation/IBS-C (n = 9)	0.57	0.39 to 0.75	< 0.001	< 0.01
Healthy (n = 8)	0.22	0.05 to 0.39	0.01
Study quality
Jadad score ≥ 3 (n = 12)	0.45	0.31 to 0.59	< 0.001	0.01
Jadad score < 3 (n = 5)	0.00	-0.33 to 0.33	> 0.99
Age1
≥ 39 yr (n = 9)	0.51	0.29 to 0.73	< 0.001	0.08
< 39 yr (n = 8)	0.27	0.09 to 0.44	< 0.01
Publication year
After 2008 (n = 10)	0.47	0.29 to 0.65	< 0.001	0.08
Before 2008 (n = 7)	0.20	-0.03 to 0.44	0.09
Number of probiotic strains
Single strain (n = 10)	0.49	0.32 to 0.66	< 0.001	0.09
Multiple strains (n = 7)	0.23	-0.01 to 0.47	0.06
Study design
Parallel groups (n = 11)	0.48	0.31 to 0.65	< 0.001	0.09
Cross-over (n = 6)	0.26	-0.02 to 0.46	0.07
Body mass index12
≥ 25 kg/m2 (n = 5)	0.59	0.24 to 0.94	< 0.001	0.16
< 25 kg/m2 (n = 7)	0.31	0.13 to 0.49	< 0.001
Treatment duration1
< 18 d (n = 8)	0.45	0.29 to 0.60	< 0.001	0.17
≥ 18 d (n = 9)	0.22	-0.06 to 0.50	0.12
Geographic location
Americas (n = 6)	0.47	0.26 to 0.67	< 0.001	0.20
Europe (n = 11)	0.28	0.07 to 0.49	< 0.01
Female gender proportion1
≥ 86% (n = 9)	0.47	0.30 to 0.64	< 0.01	0.22
< 86% (n = 8)	0.27	0.00 to 0.54	< 0.05
Confounding treatments3
Yes (n = 7)	0.46	0.24 to 0.67	< 0.001	0.32
No (n = 10)	0.30	0.10 to 0.51	< 0.01
Daily probiotic dosage1
≥ 1.610 CFU (n = 8)	0.40	0.12 to 0.67	< 0.01	0.74
< 1.610 CFU (n = 7)	0.34	0.16 to 0.52	< 0.001

¹Categorized by median value;

²Body mass index not reported for 5 treatment effects;

³Includes studies where treatment included probiotics plus fiber or non-digestible sugar. Variables sorted from lowest to highest between-groups P value; n represents the number of treatment effects. IBS-C: Irritable bowel syndrome, constipation predominant; SMD: Standardized mean difference.

Table 6 Meta-regression of study- and subject-related factors on intestinal transit time

Variable	Unit of measure	Intercept	Point estimate	Explained variance (%)	P value
Constipation/IBS-C	1 = Yes; 0 = No	0.218	0.352	38	< 0.01
Jadad score	Per 1 unit	-0.117	0.141	31	0.01
Age	Per 1 yr	-0.352	0.021	27	0.02
Female gender proportion	Per 10%	-0.045	0.055	26	0.02
Number of probiotic strains	Per 1 strain	0.618	-0.133	20	< 0.05
Body mass index1	Per 1 kg/m2	-0.526	0.037	22	0.08
Treatment duration	Per 1 d	0.392	-0.004	0	0.96
Daily probiotic dosage	Per 10 × 109 CFU	0.385	-0.001	0	0.98

¹Body mass index not reported for 5 treatment effects. Variables sorted from greatest to least explained variance.

Table 7 Subgroup analysis of probiotic strains on intestinal transit time

Probiotic strain	No. of treatment effects	SMD	95%CI	P value
B. lactis HN019	3	0.67	0.37-0.97	< 0.001
B. lactis DN-173 010	3	0.54	0.16-0.92	< 0.01
L. casei CRL 431	2	0.33	-0.10-0.75	0.14
B. lactis BB12	2	0.33	-0.10-0.75	0.14
L. rhamnosus GG	3	0.10	-0.35-0.55	0.67

Probiotic strains sorted from highest to lowest standard mean difference. SMD: Standardized mean difference.