Table 1.

Human pediatric clinical trials (randomized, double-blind, placebo-controlled) demonstrating lactobacilli and bifidobacteria effects on RV diarrhea and disease.

Probiotic bacteria species/dose	Patient age	Number of patients	Treatment regimen	Treatment outcome	Study location	Reference
Intervention studies
Lactobacillus casei sp rhamnosus strain GG (1010- 1011CFU/dose)	4-45 months (≥80% RV)	n=71	Orally twice a day during acute diarrhea	Treatment significantly decreased duration of diarrhea	Finland	(Isolauri et al., 1991)
Bifidobacterium bifidum and Streptococcus thermophilus with formula (108-35 × 108 CFU/g of formula powder)	5-24 months	n=55	Orally, every feeding during diarrhea	Treatment decreased incidence of diarrhea and RV shedding	USA	(Saavedra et al., 1994)
L. rhamnosus GG (1010 CFU/ml)	5-28 months	n=42	Twice daily for 5 days	Treatment diarrhea duration was shortened	Finland	(Isolauri et al., 1994)
L. rhamnosus GG (1010-1011CFU/dose)	13 months (mean)	n=40	Twice daily for 2 days	Treatment decreased incidence of diarrhea and voimiting	Pakistan	(Raza et al., 1995)
L. rhamnosus GG (Lactophilus), or S. thermophilus and L. delbruckii subsp. bulgaricus (Yalacta)	6-35 months	n=49	Orally twice a day for 5 days, after RV diarrhea was confirmed	LGG improved Ab and ASC responses to RV and significantly decreased mean duration of diarrhea compared to other treatments	Finland	(Majamaa et al., 1995)
L. rhamnosus GG (1010-1011CFU/dose)	8 months (mean)	n=39	Twice daily for 2 days	Treatment decreased duration of diarrhea	Thailand	(Pant et al., 1996)
L. rhamnosus GG (3 × 109 CFU/dose)	3-36 months (61% RV)	n=100	Orally twice a day during acute RV diarrhea	Treatment decreased duration of diarrhea	Italy	(Guarino et al., 1997)
L. rhamnosus GG (5 × 109 CFU/ml)	1-36 months (27% RV)	n=123	Twice daily for 5 days with ORS	Treatment significantly shortened the duration of RV diarrhea and decreased frequency of stools (but not diarrhoea with confirmed bacterial etiology)	Russia	(Shornikova et al., 1997c)
L. reuteri (107 or 1010/1011 CFU/dose)	6-36 months (89% RV)	n=97	Orally for up to 5 days	Treatment decreased duration of diarrhea in a dose-dependent manner	Finland	(Shornikova et al., 1997b)
L. reuteri DSM 17938 (1010-1011 CFU/ml)	6-36 months (75% RV)	n=40	Daily with formula for up 5 days	Treatment decreased duration of acute diarrhea	Finland	(Shornikova et al., 1997a)
L. rhamnosus GG (5 × 109 CFU/ml)	6-36 months (92% RV)	n=123	Twice daily with formulafor 5 days	Treatment decreased duration of acute diarrhea, improved weight gain, corrected acidosis	Finland	(Rautanen et al., 1998)
L. acidophilus LB (1010 CFU/dose)	3-24 months (50% RV)	n=73	Five doses every 12 hrs with ORS	Treatment decreased duration of diarrhea	Thailand	(Simakachorn et al., 2000)
L. rhamnosus GG (at least 1010 CFU/250 ml), given ad libitum	1-36 months	n=287	Orally until diarrhea stopped	Treatment significantly decreased mean duration of diarrhea	Italy	(Guandalini et al., 2000)
L. rhamnosus GG at 6 × 109 CFU	1-36 months	n=81	Orally twice daily for the duration of their hospital stay	Treatment significantly reduced the risk of rotavirus gastroenteritis (1 of 45 [2.2%] vs. 6 of 36 [16.7%] in placebo group, respectively	Poland	(Szajewska et al., 2001)
L. rhamnosus 19070-2 and L. reuteri DSM 12246 (each species 1010CFU/dose)	6-36 months	n=71	Orally twice a day for 5 days during acute diarrhea (≥80% RV)	Treatment ameliorated acute and reduced the period of rotavirus excretion	Denmark	(Rosenfeldt et al., 2002)
L. rhamnosus GG (109CFU/ml)	3-36 months (with signs of mild- moderate dehydration; 24.4% RV in LGG group and 39.3% RV in placebo group)	n=179 (all males)	Daily with formula for diarrhea duration	No significant differences in duration of diarrhea, rate of treatment failure, and proportion of unresolved diarrhea	Peru	(Salazar-Lindo et al., 2004)
B. lactis Bb12 and S. thermophilus TH4 (108 - 109 CFU/dose)	3-36 months (87% RV)	n=212	Orally during acute RV diarrhea until 24 hrs after diarrhe subsided (~3 days?)	Treatment only slightly decreased RV shedding in a dose dependent manner	China	(Mao et al., 2008)
L. rhamnosus GG (109CFU/dose)	<36 months (moderately malnourished, 25.6% RV)	n=229	For 10 days	No difference in duration of diarrhea or number of stools on days 3, 6 and 10	India	(Misra et al., 2009)
L. rhamnosus GG (109CFU/dose)	4 months - 2 years (11% RV)	n=64	Three times a day for 3 days	No differences in duration or severity of diarrhea. However, the number of diarrheic stool was significantly lower on day 2 in the treatment group	Australia, Aboroginal children	(Ritchie et al., 2010)
L. acidophilus, L. rhamnosus, B. longum and Saccharomyces boulardii (each species 9×106- 7×107CFU/dose)	1-23 months	n=64	Orally for 5 days with ORS, after RV diarrhea was confirmed	Treatment decreased duration of diarrhea and incidence of voimiting	Bolivia	(Grandy et al., 2010)
B. lactis (30mg/day)	5 months - 5 years	n=75 (38 females, 37 males)	Orally for 5 days, after RV diarrhea was confirmed	Treatment decreased duration of diarrhea	Turkey	(Erdogan et al., 2012)
L. reuteri DSM 17938 (4 × 108 CFU/ml)	6-36 months (with clinical signs of dehydration; 62% RV)	n=74	Daily with formula for 7 days	Treatment reduced the frequency, duration and recrudescence rate of acute watery diarrhea	Italy	(Francavilla et al., 2012)
L. rhamnosus GG (109CFU/capsule)	6 months - 5 years (21% RV)	n=200	One capsule/day for 7 days	Treatment reduced the duration of acute watery diarrhea	India	(Aggarwal et al., 2014)
L. rhamnosus GG (1010CFU/capsule)	6 months - 5 years (66% RV)	n=124	One capsule/day in milk for 4 weeks	Treatment reduced repeated diarrheal episodes and significantly increased RV- specific IgG levels	India	(Sindhu et al., 2014)
Prophylactic studies
L. rhamnosus GG (3.7 × 1010 CFU/ml)	6-24 months (undernourished)	n=204	Daily for 6 days/wk for 15 months	Prophylactic effect of LGG supplementation on diarrhea incidence in non-breast-fed children	Peru	(Oberhelman et al., 1999)