Table 4.

Characteristics of Studies Investigating Probiotic Administration on the Fecal Microbiota of Healthy Children Under 18 Years-of-Age

Country of Study, Age Range, Duration of Intervention	Study Design and Participants/Group	Nutrition Base and Probiotic Strain and Amount	Microbiota Assessment	Outcomes	Citation
Germany Infants at birth; 12 mo intervention	Randomized, double-blind placebo controlled trial Probiotic (n=11) Control (n=11) EBF (n=9)	Formula B. bifidum BF3 + B. breve BR3 + B. longum subsp. infantis BT1 + B. longum BGT (2.5×106CFU/strain/g)	Monthly during intervention 16S rRNA gene by Illumina MiSeq	↔ alpha- and beta-diversity ↓ relative abundances of OTUs related to B. fragilis and Blautia over the first y.	72
Finland (Tartu) Infants 0-2 mo; 6 mo intervention	Randomized, double-blind placebo controlled trial Probiotic (n= 12) Control (n=13)	Formula LGG 1.0×107 CFU/d	Entry and end of the intervention FISH	↔ colonization frequency and counts of Lactobacillus/Enterococcus, Bifidobacterium, groups of C. coccoides, C. lituseburense and C. butyricum	73
Greece (Athens) Infants ≤3d; 6 mo intervention	Randomized, double-blind placebo controlled trial Vaginal (V) or C-section (C) delivery V-Control (VCt) (n=10) CCt) (n=10) VLr (n-9) CLr (n=11)	Formula L. reuteri DSM 17938 1.2×109CFU/L	2 and 4 mo of age 16S rRNA gene by 454-pyrosequencing	Global microbiota of CSCt differed from others at 2 wk, not at 4 mo Bifidobacterium occurrence and abundance: CCt < CLr, VCt, VLr at 2 wk Proportion of unclassified Enterobacteriaceae: CCt > CLr, VCt, VLr at 2 wk Lactobacillus abundance: CLr > CCt; VLr > VCt at both time points	74
China (Shanghai) Infants at 0-7 d; 12 mo intervention	Randomized, double-blind placebo controlled trial Probiotic (n=135) Control (n=129)	Formula B. longum BB536 107 CFU/g	2, 4 and 11 mo of age Selective plating	↑ bifidobacteria level at 2 and 4 mo. ↔ count of Enterobacteriaceae at 2, 4 and 11 mo	75
Spain Infants at 1 mo; 5 mo intervention	Randomized, double-blind placebo controlled trial Probiotic (n=46) Control (n=46)	Formula + 0.3 g/100ml GOS L. fermentum CECT5716 1x107 CFU/g	3 y of age qPCR	↔ fecal counts of Lactobacillus, Bifidobacterium, C. coccoides group and B. fragilis group at 3 y of age	76
Chile (Santiago) Infants at 1 mo; 13 wk intervention	Randomized, double-blind placebo controlled trial Probiotic (n=48) FOS (n=44) Control (n=61) BF (n=46)	Formula L. johnsonii La1 108 CFU/g	7 wk of study and 2 wk post-intervention Selective plating FISH	↔ counts of Bifidobacterium, Enterobacteria, Bacteroides, Enterococcus, C. perfringens and C. histolyticum ↑ number of Lactobacillus at 7 wk	77
Denmark (ProbiComp Study) Infants at 8–13 mo; 6 mo intervention	Randomized, double-blind placebo controlled trial Probiotic (n= 103) Control (n=98)	Not reported BB-12 + LGG 109 CFU/strain/d	Before and post-intervention V3 region of 16S rRNA gene by Ion OneTouch and Ion PGM	↔ overall microbiota ↑ proportion of Lactobacillus	78
Italy Infants 12-24 mo; 4 wk intervention	Randomized, double-blind placebo controlled trial Probiotic (n=13) Control (n=13)	Fermented milk L. paracasei A 1.6 × 1010 CFU/d	Before, during (1,3, 4 wk) and 1 wk after the intervention Selective plating	↑ counts of Lactobacillus after 1 wk ↑ numbers of Bifidobacterium ↓ clostridia count after 4 wk ↔ the numbers of enterococci, Bacteroides and total anaerobes	79
U.S.A. (Washington, DC) Children 1-5 y; 10 d intervention	Randomized, double-blind placebo controlled trial Probiotic (n=29) Control (n=31)	Yogurt drink BB-12 1010 CFU/d	Prior to and on days 10, 30, 60 and 90 following the initiation of intervention V4 region of 16S rRNA gene by Illumina Genome Analyzer II	↔ overall microbiota and proportion of Bifidobacterium ↑ proportions of Prevotella and Sutterella, ↓ Allobaculum, Collinsella, Turicibacter, Enterococcus and Garnulicatella after 10 d	80
Malaysia Children 2-6 y; 10 mos intervention	Randomized, double-blind placebo controlled trial Probiotic (n=55) Control (n=61)	Freeze-dried powder B. longum BB536 5 × 109 CFU/d, 5 d/wk	0 and 10 mo of intervention V3-V4 region of 16S rRNA gene by Illumina MiSeq	Overall microbiota differed between 0 and 10 mo in BB536 group, but not in placebo ↑ Proportion of Faecalibacterium	81
Finland Children 2-7 y; 7 mos intervention	Randomized, double-blind placebo controlled trial Probiotic (n=56) Control (n=21)	Milk LGG 4 × 108 CFU/d	Beginning and end of intervention Phylogenetic microarray (HITChip)	↑relative abundance of Lactococcus, L. gasseri, R. lactaris, uncultured Mollicutes, P. melaninogenica and P. oralis ↓ E. cylindroides, C. ramosum, and E. coli	82
Italy Children 5.7 ± 2.6 y; 21 d intervention	Observational trial Probiotic (n=10)	Oily suspension LGG 4 × 108 CFU/d	Beginning and end of intervention Selective plating	↓ total coliform	83
Japan (Tokyo) Children 4-12 y; 6 mo intervention	Observational trial Probiotic (n=23)	L. casei Shirota 4 × 1010 CFU/d	Beginning and end of intervention RT-qPCR	↑counts of Bifidobacterium and Lactobacillus after 3 and 6 mo of intervention ↓ counts of Enterobacteriaceae and Staphylococcus after 3 and 6 mo of intervention ↓ detection rate of C. perfringens after 6 mo of intervention	84
Netherlands (Amsterdam) Children 12-18 y; 6 wk intervention	Observational trial Probiotic (n=6) Control (n=12)	L. casei Shirota 6.5 × 109 CFU/d	Beginning and end of intervention IS-Pro	↔ Shannon index	85

Abbreviations: BB-12, Bifidobacterium animalis subsp. lactis BB-12; BF, breast-fed; CFU, colony-forming unit; C, cesarean section; Ct, control; d, day; EBF, exclusive breast-fed; FF, formula-fed; FISH, fluorescent in situ hybridization; FOS, fructooligossacharides; LGG, Lactobacillus rhamnosus GG; IS-Pro, interspace profiling; mo; month; OTU, operational taxonomic unit; qPCR, quantitative PCR; RT-qPCR, reverse transcription quantitative PCR; V, vaginal delivery; wk week ↑indicates significantly increased; ↓ indicated significantly decreased; ↔ indicates no effect