Table 3.

Synbiotics administration in prevention of allergic disorders.

(A) Synbiotic + Standard formula/breastfeeding.
References	Study	Enrolled Patients	Synbiotic + Standard formula/ breast feeding	Prebiotic substance, Beginning of Treatment (S), End of Treatment (E).	Probiotic Strain, Beginning of Treatment (S), End of Treatment (E).	Pre-natal administration (duration)	Post-natal administration (duration)	Outcomes	Follow-Up (duration)
Kukkonen et al. (156)	double-blind randomized, placebo controlled trial	− 1223 pregnant woman carrying high- risk children and their infants: - N = 461 mothers-infants received symbiotic - N = 464 mothers-infants received placebo	- Synbiotics group: - mothers: 1 capsule containing 4 probotics twice daily - infants received 1 opened capsule containing the same probiotics mixed with galacto-oligosaccharides once daily Placebo group: capsules containing microcrystalline cellulose, and the infants received syrup without galacto-oligosaccharides	Synbiotics group: infants received 1 opened capsule containing the same probiotics mixed with drops of sugar syrup containing 0.8 g of galacto-oligosaccharides once daily S(women): 2–4 weeks before delivery E (Women): at delivery S (infants): birth E (infants): 6 months	1 capsule containing L. rhamnosus GG(ATCC 53103), 5 × 109 cfu; L. LC705 (DSM 7061), 5 × 109 cfu; B. breve Bb99(DSM 13692), 2 × 108 cfu; and P. freudenreichii ssp. shermanii JS(DSM 7076), 2 × 109 cfu, twice daily S(women): 2–4 weeks before delivery E (Women): at delivery S (infants): birth E (infants): 6 months	2–4 weeks before delivery	For 6 months	There was no effect of probiotic supplementation compared with placebo on the cumulative incidence of any allergic disease (OR, 0.85; 95% CI, 0.64–1.12). There was a reduced occurrence of Eczema in the probiotic group (OR, 0.74; 95% CI, 0.55–0.98)	2 years
Roze et al. (181)	double-blind, randomized, multicenter trial	Ninety-seven non-brestfed term neonates:	Symbiotics group (n 48): Standard formula + symbiotics Control group(n 49): standard formula	experimental formula containing the two strains of probiotics +96% galacto-oligosaccharides and 4 % short-chain fructo-oligosaccharides	experimental formula containing L. rhamnosus LCS- 742(1.4 × 108), B. longum subsp infantis M63 (1.4 × 108) and prebiotics:	no	For 6 months	Atopic dermatitis was less frequently observed in the experimental group (2.6% vs. 17.8%, P < 0.05)	6 months
(B) Synbiotic +Hydrolyzed/ amino acid-based formulas.
Refereences	Study	Enrolled patients	Hydrolyzed/ amino acid-based formulas+synbiotic	Prebiotic substance, Beginning of treatment (S), End of treatment (E).	Probiotic strain, dose Beginning of treatment (S), End of treatment (E).	Pre-natal administra-tion (duration)	Post-natal administration (duration)	Outcomes	Follow-up (duration)
van der et al. (182)	double-blind, placebo-controlled multicentre trial	ninety full-term infants, aged <7 months with AD	Synbiotic group: extensively hydrolyzed whey-based formula with additional synbiotics [B. breve M-16V and a galacto/fructooligosaccharide mixture] Control group: same formula without synbiotics	mixture of 90% scGOS and 10% lcFOS 0.8 g/100 ml S: <7 month E: after 12 weeks	B. breve M-16V (1.3 × 109 cfu/100 ml) S: <7 month E: after 12 weeks	no	12 weeks	The SCORAD score improvement (AD severity) did not differ between the synbiotic and the placebo group. In the synbiotic group there was a significantly higher percentage of bifidobacteria (54.7% vs. 30.1%, P < 0.001) and significantly lower percentages of Clostridium lituseburense /Clostridium histolyticum (0.5 vs. 1.8, P = 0.02) and Eubacterium rectale /Clostridium coccoides (7.5 vs. 38.1, P < 0.001) after intervention than the placebo group	12 weeks
van der et al. (183)	double-blind, placebo-controlled multicentre trial	ninety full-term infants, aged <7 months with AD	Synbiotic group: extensively hydrolyzed whey-based formula with additional synbiotics [B. breve M-16V and a galacto/fructooligosaccharide mixture] Control group: same formula without synbiotics	mixture of 90% scGOS and 10% lcFOS 0.8 g/100 ml S: <7 month E: after 12 weeks	B. breve M-16V (1.3 × 109 cfu/100 ml) S: <7 month E: after 12 weeks	no	12 weeks	infants in the synbiotics group have a lower prevalence of asthma-like symptoms (frequent wheezing) and asthma medication use at 1-year follow-up than those who received placebo [13.9% vs. 34.2%, absolute risk reduction (ARR)]20.3%, 95% CI −39.2% to −1.5% and (5.6% vs. 25.6%, ARR−20.1%, 95% CI −35.7% to −4.5%)	1 years
Candy et al. (184)	multicenter, double-blind, randomized controlled trial	Term infants <13 months old, with suspected non-IgE-mediated CMA	Symbiotic group (N = 35): amino-acid-based formula (AAF) contained a prebiotic blend and a probiotic strain control group (N = 36): commercially available AAF	chicory-derived neutral oligofructose, long-chain inulin (9:1 ratio at a total concentration of 0.63 g/100 ml S: <13 months E: after 8 weeks	Bifidobacterium breve M-16V) at a concentration of 1.47 × 109 CFU/100 mL S: <13 months E: after 8 weeks	no	8 weeks	There was a significantly higher median percentage of Bifidobacteria w (p < 0.001) in the test group than in the control subjects (35.4% vs. 9.7%), whereas a lower percentage of Eubacterium rectale/Clostridium coccoides group in feces (9.5% vs. 24.2%) and similar to that detected in breastfed infants (55% and 6.5%, respectively). There was no statistically significant changes over 8 weeks in the reported scores for skin symptoms. SCORAD decreased between weeks 0 and 8, from 12.83 ± 18.84 to 9.63 ± 12.45 in the test group and from 14.43 ± 19.74 to 7.06 ± 10.01 in the control group	8 weeks
Fox et al. (185)	double-blind, randomized, controlled multicenter trial	Term infants <13 months old, with suspected non-IgE-mediated CMA	Symbiotic group (N = 35): amino-acid-based formula (AAF) contained a prebiotic blend and a probiotic strain control group(N = 36): commercially available AAF Healthy reference group (N = 51)	chicory-derived neutral oligofructose, long-chain inulin (9:1 ratio at a total concentration of 0.63 g/100 ml) S: <13 month E: after 8 weeks	Bifidobacterium breve M-16V at a concentration of 1.47 × 109 CFU/100 mL S: <13 month E: after 8 weeks	no	8 weeks	The supplementation of AAF with specific synbiotics induced a sustained improvement in gut microbiota composition. The median percentages of bifidobacteria were significantly higher at week 26 in the test group than controls [47.0% vs. 11.8% (p < 0.001)], whereas percentages of ER/CC were significantly lower [(13.7% vs. 23.6% (p = 0.003)]. The use of dermatological medication and reported ear infections were lower in test vs. control, p = 0.019 and 0.011, respectively	26 weeks