Table 1.
Prebiotics administration in prevention of allergic disorders.
| (A) Prebiotic + Standard formula (or prebiotic of human milk). | ||||||
|---|---|---|---|---|---|---|
| References | Study | Enrolled patients | Prebiotic + Standard formula (or prebiotic of human milk) |
Prebiotic substance, Beginning of treatment (S), End of treatment (E). |
Outcomes | Follow-up (duration) |
| Ziegler et al. (82) | double-blind, randomized, controlled, parallel-group, prospective trial | 226 healthy term infants in 3 groups: - 58 in control group: control formula only - 58 in PG4 group: control formula +4 g/L prebiotic mixture - 48 in PGL8 group: control formula +8 g/L prebiotic mixture |
Control formula added with a prebiotic mixture (4 g/L) of PDX and GOS, 50:50 ratio (PG4 group) Control formula containing a prebiotic mixture (8 g/L) of PDX, GOS, and LOS, 50:33:17 ratio). (PGL8 group) |
S: 14 days of age E: 120 days of age |
Infants fed formula containing a prebiotic mixture achieved normal growth and stool characteristics more similar to those of breast-fed infants (softer, looser) compared to infants fed an unsupplemented formula. Statistical difference among adverse events: - Eczema (PG4 vs. control: 18 vs. 7%, P = 0.046; PG4 vs. PGL8: 18 vs. 4%, P = 0.008) - Diarrhea: control vs. PG4: 4 vs. 18%, P = 0.008) - Irritability: control vs. PGL8, 4 vs. 16%, P = 0.027) |
120 days |
| Niele et al. (83) | Double-blind, randomized placebo controlled trial | 113 preterm infants (GA < 32 weeks or Wt < 1.500 gr) 94/98 infants eligible at the corrected age of 1 year participated in the follow-up study |
Prebiotic mixture: 80% scGOS/lcFOS and 20% pAOS Placebo mixture: maltodextrin in increasing dose for 30 days. After discharge, all infants received Human Milk or Nenatal Start or Nenatal 1 (both without oligosaccharides or probiotics) |
S: < 3days of life E: 30 days of life |
Supplementation with non-human neutral and acidic oligosaccharides during the neonatal period in preterm infants did not significantly decrease the incidence of allergic and infectious diseases during the 1st year of life (AD at 1 year: 15 vs. 19%) |
12 months |
| Gruber et al. (84) | double-blind, placebo-controlled, randomized prospective nutritional intervention study | Healthy term infants with low atopy risk: - 414 infants in prebiotic group (PG) - 416 infants in control group (CG). - 300 infants in breast-feeding group (BG) |
PG: regular formula containing a specific mixture of neutral oligosaccharides [scGOS/lcFOS, ratio 9:1, (85 wt%),] and pectin-derived acidic oligosaccharides OS) (15wt%) CG: Standard formula without oligosaccharides. BG: Breast milk |
S: before post-natal age of 8 weeks E: 12 months |
Formula containing a mixture of neutral oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants (5.7% in PG vs. 9.7% in CG, P = 0.04; 7.3% in BG) | 1 year |
| Gruber et al. (85) | double-blind, controlled, randomized prospective nutritional intervention study | Healthy term infants with low atopy risk: - 232 infants in prebiotic formula group (PG) - 243 infants in control formula group (CG) - 197 infants in breast-feeding group (BG) |
PG: regular formula containing aspecific mixture of neutral oligosaccharides [scGOS/lcFOS, ratio 9:1, (85 wt%),] and pectin-derived acidic oligosaccharides OS)(15wt%) CG: Standard formula without oligosaccharides. BG: Breast milk |
S: before post-natal age of 8 weeks E: 12 months |
The cumulative incidence of AD up to age 5 years was 18.2% (PG) 20.2% (CG) and 23.9% (BG), therefore in this follow up study there was no sustained statistically significant effect of prebiotics added to infant diet against the occurrence of early AD at preschool age | 5 years |
| Pontes et al. (86) | double-blind, randomized, controlled trial | healthy children (1–4 years of age) 125: CMBB with DHA,PDX,GOS, β-glucan, and other key nutrients 131: control |
Cow's Milk-Based Beverage (CMBB) containing DHA, the prebiotics polydextrose (PDX) and galactooligosaccharides (GOS), β-glucan, and other nutrients including zinc, vitamin A and iron | S: 1–4 years of age E: 28 weeks later |
CMBB was associated with fewer episodes of allergic manifestations (atopic dermatitis, wheezing, allergic rhinitis) compared to controls (p = 0.021) | 28 weeks. |
| Ranucci et al. (87) | randomized, double-blind, placebo-controlled trial | 118/201 infants who received a prebiotic (GOS/PDX)-enriched formula (PF) completed the study 104/199 infants who received an SF until 48 weeks of life completed the study 123/140 infants who remained on exclusive breastfeeding until six months of age completed the study |
prebiotic (mixture of 4 g/L of GOS/PDX)-enriched standard formula (PF) vs. identical standard formula without prebiotic | S: birth E: 48 weeks of life |
There were not significant differences in the cumulative incidence, intensity and duration of AD among groups. However, the risk of AD in PF was reduced by 35% compared with SF. Bifidobacteria and Clostridium clusterI colonization increased in the PF group. Bifidobacteria was associated with RIs protection, whereas Clostridium cluster I had a protective role in atopy development |
96 weeks |
| (B) Prebiotic +Hydrolyzed/ amino acid-based formulas. | ||||||
| References | Study | Enrolled patients | Hydrolyzed/ amino acid-based formulas+ Prebiotic substance |
Prebiotic substance, Beginning of treatment (S), End of treatment (E). |
Outcomes | Follow-up (duration) |
| Moro et al. (80) | Prospective randomized, double-blind placebo controlled trial | 206/259 infants at high risk of atopy completed the study: 102 infants in the prebiotic group; 104 infants in the placebo group |
Extensively hydrolysed cows'milk whey protein formula supplemented either with 8 g/L scGOS/lcFOS / (prebiotic group) or a 8 g/L maltodextrin (placebo group) | 8 g/L scGOS/lcFOS S: within the first 2 weeks of life E: 6 months |
The cumulative incidence of AD atopic dermatitis was significantly reduced at 6 months of age by prebiotics supplementation (9.8 vs. 23.1%, p < 0.05) | 6 months |
| Arslanoglu et al. (88) | Prospective randomized, double-blind placebo controlled trial | 134/152 infants at high risk of atopy completed the study 66 in the prebiotic group 68 in the placebo group |
Extensively hydrolysed cows'milk whey protein formula supplemented either with 8 g/L scGOS/lcFOS / (prebiotic group) or a 8 g/L maltodextrin (placebo group). | 8 g/L scGOS/lcFOS S: within the first 2 weeks of life E: 6 months |
Cumulative incidences of AD, recurrent wheezing, and allergic urticaria were significantly reduced at 2 years of age by prebiotics supplementation (13.6%, 7.6%, and 1.5 vs. 27.9%, 20.6% and 10.3% respectively, p < 0.05) | 2 years |
| Arslanoglu et al. (89) | Prospective randomized, double-blind placebo controlled trial, | 92 infants at high risk of atopy completed the study 42 in the prebiotic group 50 in the placebo group |
Extensively hydrolysed cows'milk whey protein formula supplemented either with 8 g/L scGOS/lcFOS / (prebiotic group) or a 8 g/L maltodextrin (placebo group). | 8 g/L scGOS/lcFOS S: within the first 2 weeks of life E: 6 months |
Cumulative incidences of any allergic manifestations and atopic dermatitis were significantly reduced at 5 years of age by prebiotics supplementation (30.9%, and 19.1 vs. 66 and 38%, respectively, p < 0.05) | 5 years |
| Francavilla et al. (90) | Prospective two-phases clinical trial (cross-over design) | 21 infants with a confirmed CMA 15 healthy breast-fed infants as controls |
Phase 1: extensively hydrolyzed formula without lactose for 2 months Phase 2: an identical extensively hydrolyzed formula containing lactose (3.8%) for an additional 2 months |
3.8% Lactose | The addition of lactose to an extensively hydrolyzed formula increased the total fecal counts of Lactobacillus/Bifidobacteria, the concentration of total short-chain fatty acids, mostly acetic and butyric acids and decreased the counts of Bacteroides/Clostridia | 4 months |
| Boyle et al. (91) | double-blind, randomized, controlled parallel-group nutritional intervention trial | 863 high-risk infants: - 432 infants in the prebiotic group (PG) - 431 Infants fed with standard foumula (CG |
PG: partially hydrolysed whey-based infant formula containing a specific mixture of neutral scGOS and lcFOS (9: 1; 85 weight per cent, 0.68 g/100 ml) and acidic pAOS (15 weight per cent, 0.12 g/100 ml acidic) (pHF-OS) | S: before 18 weeks of life E: 6 months |
pHF-OS did not prevent eczema in high-risk infants in the first 12 months (Eczema occurred in 30.8% pHF-OS vs. 30.3% control in all infants (OR 0.99 95% CI 0.71, 1.37; P = 0.94). as well as by 18 months. However, pHF-OS reduced cow's milk-specific IgG1 (P < 0.0001) | 12 and 18 months |
| Wopereis et al. (92) | Double-blind, randomized, controlled, parallel group nutritional intervention trial | 138 Infants at high risk: - 51 infants in the prebiotic group (PG) - 57 Infants fed with standard foumula (CG) - 30 infants in the breast-fed group (BG) |
PG: Partially hydrolyzed formula containing short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (9:1; 0.68 g/100 mL) and pectin-derived acidic oligosaccharides (0.12 g/100 mL) CG: standard formula BG: breast milk |
S: before 18 weeks of life E: 26 weeks of age |
Infants with eczema at 18 months: 32% in CG, 39% in PG and 47% in BG Infants presenting eczema at 18 months showed a decrease in acquisition of Eubacterium and Anaerostipes species with increased lactate and reduced butyrate levels |
18 months |
Cow's milk protein allergy (CMA), Healthy controls (HC), Human milk oligosaccharides (HMO), short-chain galactooligosaccharides (scGOS), long-chain fructooligosaccharides(lcFOS), human milk oligosaccharides (HMOS), prebiotics polydextrose (PDX), galactooligosaccharides (GOS), galacto-oligosaccharide/polydextrose (GOS/PDX), Probiotic formula (PF), atopic dermatitis (AD), cow's milk-based beverage (CMBB).
Standard formula (SF), Breast feeding (BF).