Table 2.
Probiotics administration in prevention of allergic disorders.
| (A) Probiotic given orally (eg droplets, suspensions, capsules) or with breastfeeding/ standard formula. | ||||||||
|---|---|---|---|---|---|---|---|---|
| References | Study | Enrolled patients | Probiotic + Standard formula/breast Feeding |
Probiotic strain, Beginning of treatment (S), End of treatment (E). |
Pre-natal administra-tion (duration) | Post-natal administration (duration) | Outcomes | Follow-up (duration) |
| Kalliomaki et al. (109) | double-blind, randomized, placebo-controlled trial | − 159 Pregnant woman who had at least one first-degree relative (or partner) with atopic disease - breastfeeding mothers - their infants, post-natally if not breast-fed |
Placebo group (n = 82): two capsules of placebo (microcrystalline cellulose) Probiotic group (n = 77): two capsules of 1 × 1010 CFU of Lactobacillus GG daily: for infants contents were mixed with water and given by spoon |
Pregnant woman: S: 2–4 weeks before expected delivery E: at delivery or 6 months later if breastfeeding mothers Infants: S: birth E: 6 months |
2–4 weeks before expected delivery | 6 months | There was a halving in frequency of atopic eczema in the probiotic group compared with the placebo group (15/64 [23%] vs. 31/68 [46%]; relative risk 0.51 [95% CI 0.32–0.84]). The number needed to treat was 4.5 (95% CI 2.6–15.6) | 2 years |
| Rautava et al. (111) | parallel, double-blind placebo-controlled trial | 205 pregnant women with allergic disease and atopic sensitization | Probiotic groups: - 1 sachet of L.rhamnosus LPR (1 × 109 CFU) and B. longum BL999 (1 × 109 CFU (N = 73) daily or - L paracasei ST11 (1 × 109 CFU) and B longum BL999 (1 × 109 CFU) daily (N = 70) Placebo group (n = 62): the same sachet without probiotics |
S: 2 months before expeted delivery E: 2 months after delivery (during breast-feeding) |
2 months before expeted delivery to delivery | 2 months | There was a significantly reduced risk of developing eczema in infants of mothers receiving LPR1BL999 (odds ratio [OR], 0.17; 95% CI, 0.08-0.35; P <.001) and ST111BL999 (OR, 0.16; 95% CI, 0.08–0.35; P <.001) | 2 years |
| Kalliomäki et al. (112) | double-blind, randomi-zed, placebo-controlled trial | - 132 Pregnant woman who had at least one first-degree relative (or partner) with atopic disease -breastfeeding mothers - their infants, post-natally if not breast-fed |
Placebo group (n = 53): two capsules of placebo (microcrystalline cellulose) Probiotic group (n = 54): two capsules of 1 × 1010 CFU of Lactobacillus GG daily: for infants contents were mixed with water and given by spoon |
Pregnant woman: S: 2–4 weeks before expected delivery E: at delivery or 6 months later if breastfeeding mothers Infants: S: birth E: 6 months |
2–4 weeks before expected delivery | 6 months | There was an extention beyond infancy of the preventive effect of lactobacillus GG on atopic eczema: (14/53 in probiotic group developped eczema vs. 25/54 receiving placebo (relative risk 0.57, 95% CI 0.33–0.97) | 4 years |
| Kalliomäki et al. (113) | double-blind, randomized, placebo-controlled trial | - 116 Pregnant woman who had at least one first-degree relative (or partner) with atopic disease -breastfeeding mothers -their infants, post-natally if not breast-fed | Placebo group (n = 62): two capsules of placebo (microcrystalline cellulose) Probiotic group (n = 53): two capsules of 1 × 1010 CFU of Lactobacillus GG daily: for infants contents were mixed with water and given by spoon |
Pregnant woman: S: 2–4 weeks before expected delivery E: at delivery or 6 months later if breastfeeding mothers Infants: S: birth E: 6 months |
2–4 weeks before expected delivery | 6 months | The cumulative risk for developing eczema was significantly lower in the L.GG group than in the placebo group (42.6% vs. 66.1%; RR, 0.64; 95% CI, 0.45-0.92) According to Cox regression, the risk of eczema was significantly reduced in the L. GG group (odds ratio, 0.58; 95% CI, 0.35–0.94; P = 0.027) | 7 years |
| Wickens et al. (114) | Double-blind, randomized placebo-controlled trial | - Pregnant women who had at least one first-degree relative (or partner) with atopic disease,- breast feeding mothers -their infants | Two Probiotic groups(capsule powder with): - Lactobacillus rhamnosus HN001 (N = 170) - Bifidobacterium animalis subsp lactis strain HN019 (N = 171) Placebo group: (N = 171): capsule powder without probiotics |
Pregnant women: Lactobacillus rhamnosus HN001 (6 x 3 109 CFU /d), Bifidobacterium animalis subsp lactis strain HN019 (9 x 3 109 CFU /d) or placebo daily from 35 weeks gestation until 6 months if breast-feeding Infants: same treatment from day 2-16 of life to 2 years |
From 35 weeks gestation | Breast feeding mothers: for 6 months Infants: for 2 years since day 2-16 of life |
infants receiving L rhamnosus had a significantly (P = 0.01) reduced risk of eczema (hazard ratio [HR], 0.51; 95% CI, 0.30–0.85) compared with placebo, but this was not the case for B animalis subsp lactis (HR, 0.90; 95% CI, 0.58–1.41) | 2 years |
| Dotterud et al. (115) | randomized, double-blind trial | 415 pregnant women | Probiotic group (n = 138): probiotic milk contained LGG 5 × 1010 CFU, Bb-12 5 × 1010 CFU and La-5. 5 × 109 CFU daily. Placebo group (N = 140): the placebo milk contained no probiotic bacteria |
S: 4 weeks before expected delivery date E: 3 months after delivery (while breastfeeding) |
4 weeks (from 36 weeks of gestation) | 3 months while brestfeeding | There was a odds ratio (OR) of 0.51 for the cumulative incidence of AD in the probiotic group compared with the placebo [95% CI, 0.30–0.87; P = 0.013]. There were no significant effects on asthma or atopic sensitiza- tion | 2 years |
| Kim et al. (116) | randomized, double-blind, placebo-controlled trial | 112 pregnant women and newborns | Probiotics group: mixture of B. bifidum BGN4 [1.6 × 109CFU], B. lactis AD011 (1.6 × 109 CFU), and L. acidophilus AD031 (1.6 × 109 CFU) in 0.72 g of maltodextrin and 0.8 g of alpha-corn once daily Placebo group: maltodextrin and alpha-corn without probiotic bacteria |
S (women): 4–8 weeks before expected delivery E (women): 3 months after delivery (during breastfeeding) S (infants): 4 months after delivery E(infants): 6 months |
4–8 weeks before expected delivery to delivery | 6 months | There was a significant reduction in the cumulative incidence of eczema during the first year in probiotic group (36.4% vs. 62.9%, p = 0.029) | 1 year |
| West et al. (117) | double-blind, placebo-controlled randomized intervention trial | 179 infants during weaning | Probiotic group (n = 89): fed cereals with Lactobacillus F19 Placebo group(N = 90): fed cereals without probiotics |
S: 4 months E: 13 months |
no | 9 months | There was a cumulative incidence of eczema of 11% (4–17%, 95% CI) in the probiotic group vs. 22% (13–31%, 95% CI) in the placebo group (p < 0.05) | 13 months |
| Lodinova-Zadnikova et al. (118) | controlled clinical trial | 158 infants: - N = 56 colonized infants of allergic mothers, N = 57 control infants of allergic mothers - N = 45 control infants of healthy mothers |
One milliliter of E. coli was administered to infants of allergic mothers | S: within 48 h after birth and subsequently 3 times a week E: 4 weeks |
no | 4 weeks | There were allergy symptoms in 14 infants of control allergic mothers, in 7 infants of healthy mothers, and in 2 colonized infants of allergic mothers | 5 years |
| Ezaki et al. (119) | Retrospective study | 30 newborns after small intestine surgery | Probiotic group (N = 18 newborns GA 34.5 (23.5–38.4): suspension of B. breve
(7.5 × 108 cells/day). Placebo group (N = 12 newborn, GA 34.4 (26.4–40.0): |
S: After small intestine sugery E: when full enteral feeding (100 ml/kg/day) was reached |
no | After small intestine surgery until full enteral feeding (100 ml/kg/day) was reached |
Administration of probiotics reduced the incidence of cow's milk protein intolerance (CMPI) after small intestine surgery (one vs. eight, p < 0.001) | |
| Wickens et al. (120) | Double-blind, randomized placebo-controlled trial | - Pregnant women who had at least one first-degree relative (or partner) with atopic disease, -breast feeding mothers -their infants (N = 425) | Two Probiotic groups: - Lactobacillus rhamnosus HN001 - Bifidobacterium animalis subsp lactis strain HN019 Placebo group: |
Pregnant women: Lactobacillus rhamnosus HN001 (6 × 3 109 CFU/d), Bifidobacterium animalis subsp lactis strain HN019 (9 × 3 109 CFU/d) or placebo daily from 35 weeks gestation until 6 months if breast-feeding Infants: same treatment from day 2-16 of life to 2 years |
From 35 weeks gestation | Breast feeding mothers: for 6 months Infants: for 2 years since day 2–16 of life |
The cumulative prevalence of eczema [Hazard ratio (HR) 0.57 (95% CI 0.39–0.83)] and prevalence of rhinoconjunctivitis [Relative risk 0.38 (95% CI 0.18–0.83)] were significantly reduced in the children taking HN 001; HN 019 did not affect the prevalence of any outcome | 4 years |
| Wickens et al. (121) | Double-blind, randomized placebo-controlled trial | - Pregnant women who had at least one first-degree relative (or partner) with atopic disease, -breast feeding mothers -their infants (N = 425) | Two Probiotic groups: - Lactobacillus rhamnosus HN001 - Bifidobacterium animalis subsp lactis strain HN019 Placebo group: |
Pregnant women: Lactobacillus rhamnosus HN001 (6 × 3 109 CFU/d), Bifidobacterium animalis subsp lactis strain HN019 (9 × 3 109 CFU/d) or placebo daily from 35 weeks gestation until 6 months if breast-feeding Infants: same treatment from day 2-16 of life to 2 years |
From 35 weeks gestation | Breast feeding mothers: for 6 months Infants: for 2 years since day 2–16 of life |
HN001 was associated with significantly lower cumulative prevalence of eczema (HR = 0.56, 95% CI 0.39–0.80), SCORAD ≥ 10 (HR = 0.69, 0.49-0.98) and SPT sensitization (HR = 0.69, 95% CI 0.48–0.99). HN019 had no significant effect on any outcome | 6 years |
| Wickens et al. (122) | Double-blind, randomized placebo-controlled trial | - Pregnant women who had at least one first-degree relative (or partner) with atopic disease, -breast feeding mothers -their infants | Two Probiotic groups: - Lactobacillus rhamnosus HN001 (N = 97) - Bifidobacterium animalis subsp lactis strain HN019 (N = 104) Placebo group: (N = 97) The capsule powder was either given undiluted to the infant or mixed with water, breast milk, or formula and given via a teaspoon or syringe or sprinkled on food. |
Pregnant women: Lactobacillus rhamnosus HN001 (6 × 3 109 colony-forming units/d), Bifidobacterium animalis subsp lactis strain HN019 (9 × 3 109 colony-forming units/d) or placebo daily from 35 weeks gestation until 6 months if breast-feeding Infants: same treatment from day 2-16 of life to 2 years |
From 35 weeks gestation | Breast feeding mothers: for 6 months Infants: for 2 years since day 2–16 of life |
HN001 significantly reduced the 12-month prevalence of eczema at age 11 years (relative risk [RR] = 0.46, 95% CI 0.25-0.86, P = 0.015) and hay fever (RR = 0.73, 95% CI 0.53–1.00, P = 0.047). HN001 was associated with a significant reduction in lifetime prevalence of atopic sensitization (hazard ratio [HR] = 0.71, 95% CI 0.51–1.00, P = 0.048), eczema (HR = 0.58, 95% CI 0.41–0.82, P = 0.002) and wheeze (HR = 0.76, 95% CI 0.57–0.99, P = 0.046). HN019 had no significant effect | 11 years |
| Bertelsen et al. (123) | large, prospecti-ve pregnancy cohort study | 40,614 mothers and children | probiotic milk products containing L. acido-philus LA-5, B. lactis Bb12, +/- L. rhamno-sus GG | S(mother): during pregnancy S(infants): after 6 months E: 18 months |
during pregnancy | Mothers: during breast-feeding Infants: from 6 to 18 months of age |
Consumption of probiotic milk in pregnancy was associated with a slightly reduced risk [(adjusted RR (aRR)] of atopic eczema at 6 months aRR=0.94 (95% CI: 0.89, 0.99) and of rhinoconjuctivitis between 18 and 36 months, aRR=0.87 (95% CI: 0.78, 0.98); the adjusted relative risk of rhinoconjunctivitis was aRR=0.80 (95% CI: 0.68, 0.93) when both mother and infant had consumed probiotic milk | 36 months |
| Simpson et al. (124) | Double-blinded, randomized placebo-controlled trial | 161 pregnant women | Probiotic group (N = 81): probiotic milk contained LGG 5 × 1010 CFU, Bb-12 5 × 1010 CFU and La-5. 5 × 109 CFU daily. Placebo group (N = 80): the placebo milk contained no probiotic bacteria |
S: 4 weeks before expected delivery date E: 3 months after delivery (while breastfeeding) |
4 weeks (from 36 weeks of gestation) | 3 months while brestfeeding | There was a trend toward a lower cumulative incidence of AD in the probiotic group (OR 0.64, 95 % CI 0.39–1.07, p = 0.086; NNT = 10). This finding was statistically significantly in the complete case analysis (OR 0.48, 95 % CI 0.25–0.92, p = 0.027, NNT = 6) | 6 years |
| Schmidt et al. (126) | double-blind, placebo-controlled intervention trial | 290 infants aged 8 to 14 months (Mean age 10.1 months) | Probiotic group (N = 144): B. animalis subsp lactis and L. rhamnosus (109 CFU of each) daily + maltodextrin powder Placebo group (N = 146): maltodextrin powder |
S: up to 12 weeks before expected start in child care. E: after 6 months |
no | 6 months | A significantly lower incidence of eczema was observed in the probiotic group compared to the placebo group (4.2% vs. 11.5%, P = 0.036). The incidence of asthma, rhinitis, conjunctivitis, and sensitization did not differ | 6 months |
| Peldan et al. (127) | double-blinded, placebo-control-led study | 1223 mothers with infants at high risk for allergy | 445 mothers received probiotic‘s mixture: LGG (5 × 109 cfu), L rhamnosus LC705 (5 × 109 cfu), B. breve Bb99 (2 × 108 cfu), and Propionibacterium freudenreichii ssp. shermanii JS (2 × 109 cfu) twice daily. Their infants received the same probiotic capsule + syrup containing 0.8 g of galacto-oligosaccharides once daily 446 mothers and infants received capsules containing microcrystalline cellulose, (placebo) and the infants also received syrup without galacto-oligosaccharides |
S (women): From 36 weeks of gestation, E (women): at delivery S (infants): birth E (infants): 6 months |
From 36 weeks of gestation, | from birth until age 6 months. | the prevalence of allergic rhino-conjunctivitis was greater in the probiotic group compared to the placebo group (36.5% vs. 29.0%, OR: 1.43, 95% CI: 1.06–1.94, p = 0.03 | 5-10 years |
| Taylor et al. (128) | Randomized, double-blind, placebo-controlled trial | 178 newborns at high risk of allergy: - Probiotic group (n = 89) - Placebo group(n = 89) |
Probiotic group: 3 × 109 L. acidophilus LAVRI-A1 once a day(in sachet packets) Placebo group: Maltodrexine |
S: births E: 6 months |
no | 6 months | Early probiotic supplementation with L acidophilus did not reduce the risk of AD at 12 months of age (38/88 vs. 34/87 in the placebo) and was associated with increased allergen sensitization (35/88 vs. 21/86) | 12 months |
| Abrahamsson et al. (129) | prospective double-blind, placebo-controlled, multicenter trial | 188 mothers with allergic disease Their infants continued with the same product |
Probiotic group: oil + L reuteri ATCC 55730 (1 × 108 CFU) daily Placebo group: (CFUs): the same oil without probiotics |
S (Women): 36 weeks of gestational age E (women): delivery S (infants): at birth E (infants):12 months |
from gestational week 36 until delivery. | 12 months | The cumulative incidence of eczema was similar, 36% in the treated vs. 34% in the placebo group. The probiotic group had less IgE-associated eczema during the second year, 8% vs. 20% (P = 0.02), | 2 years |
| Kopp et al. (130) | Randomized, Double-Blind, Placebo-Controlled Trial | - 94 pregnant women with a family history of atopic disease - 89 breastfeeding mothers -their infants (n = 94: 5 not breastfeed infants from birth, 89 from the age of 3 months) |
L-GG group: 1 capsule(5 × 109 CFU) of L- GG twice Daily (N = 50) Placebo group: capsules of microcrystalline cellulose (N = 44) |
S (women): 4 to 6 weeks before expected delivery, then during breastfeeding for 3 months; S (infants): 5 infants from birth, 89 from the age of 3 months E(women): at delivery or after 3 months if breastfeeding E (infants): 6 months of age |
4-6 weeks | 6 months | Supplementation with L- GG neither reduced the incidence of AD (28% vs. 27.3%, P = 0.93) nor altered the severity of AD but was associated with an increased rate of recurrent wheezing bronchitis (26% vs. 9.1% P = 0.03) | 2 years |
| Prescott et al. (131) | Randomized, double-blind, placebo-controlled trial | 153 newborns at high risk of allergy: - Probiotic group (N = 74) - Placebo group (N = 76) |
Probiotic group: 3 × 109 L. acidophilus LAVRI-A1 once a day(in sachet packets) Placebo group: Maltodrexine |
S: births E: 6 months |
no | 6 months | Supplementation with this probiotic did not reduce the risk of dermatitis (31/74, 42%) compared with placebo group (25/76, 34%). There was no significant reduction in any other allergic disease or allergen sensitization | 2.5 years |
| Kuitunen et al. (133) | double-blinded, placebo-control-led study | 1223 mothers with infants at high risk for allergy | 445 mothers received probiotic ‘s mixture: LGG (5 x109 cfu), L rhamnosus LC705 (5 × 109 cfu), B. breve Bb99 (2 x108 cfu), and Propionibacterium freudenreichii ssp. shermanii JS (2 × 109 cfu) twice daily. Their infants received the same probiotic capsule + syrup containing 0.8 g of galacto-oligosaccharides once daily 446 mothers and infants received capsules containing microcrystalline cellulose, (placebo) and the infants also received syrup without galacto-oligosaccharides |
S (women): From 36 weeks of gestation, E (women): at delivery S (infants): birth E (infants): 6 months |
From 36 weeks of gestation, | from birth until age 6 months | No significant difference appeared in frequencies of eczema (39.3% vs. 43.3%), atopic eczema (24.0% vs. 25.1%), allergic rhinitis (20.7% vs. 19.1%), or asthma (13.0% vs. 14.1%) between groups. However, less IgE-associated allergic disease occurred in cesarean- delivered children receiving probiotics (24.3% vs. 40.5%; odds ratio, 0.47; 95% CI, 0.23% to 0.96%; P 5.035) | 5 years |
| Niers et al. (134) | Double-blind, randomized, placebo-controlled trial | 98 pregnant women with a family history of allergic diseases and their infants | Probiotic group (N = 50): sachets containing B. bifidum (1 × 109 CFU), B. lactis (1 × 109 CFU), and L. lactis (1 × 109 CFU) daily Placebo group (N = 48): rice starch and maltodextran |
S: last 6 weeks of pregnancy E: 12 months after delivery (to infants) |
last 6 weeks of pregnancy | 12 months | Cumulative incidence of eczema at 1 and 2 years was 23/50 (intervention) vs. 31/48 (placebo) and 27 (intervention) vs. 34 (placebo), respectively | 2 years |
| Boyle et al. (135) | Randomized controlled trial | 250 pregnant women carrying infants at high risk of allergic disease | Probiotic group: Lactobacillus rhamnosus GG (LGG) 1.8 × 1010 CFU/day Placebo group |
S: 36 weeks of gestation E: at delivery |
From 36 weeks of gestation until delivery | no | Pre-natal probiotic treatment was not associated with reduced risk of eczema (34% probiotic, 39% placebo; RR 0.88; 95% CI 0.63, 1.22) or IgE-associated eczema (18% probiotic, 19% placebo; RR 0.94; 95% CI 0.53, 1.68) | |
| Ou et al. (136) | randomized, double-blind, placebo-controlled trial | 191 pregnant women with atopic diseases, breastfeeding mothers or non-breastfeeding neonates, | Probiotic group (N = 95):LGG ATCC 53103, 1 × 1010 CFU daily Control group (N = 96) |
S (women): from the second trimester of pregnancy; E: 6 months after delivery (breastfeeding mothers or non-breast-feeding infants from birth) |
From the 24 weeks of gestational age to delivery | 6 months | There was no significant difference between the cumulative risk of sensitization and developing allergic disease at the age of first 36 months by log-rank test (P = 0.86 and P = 0.74, respectively) | 3 years |
| Damm et al. (137) | Controlled interventional cohort study | 527 preterm neonates (<30 weeks of gestation) | Probiotic group (N = 249): L. rhamnosus GG (1 × 109) and B. animalis subsp. lactis (BB12) (1 × 108) daily Control group (N = 278): not treated with probiotics |
S: third day of life E: at discharge from hospital, |
no | from the third day of life to discharge from hospital | The prevalence of AD was similar in the two groups (20.9% in the probiotic treated group vs. 17.1% in the not treated group, p = 0.33) | 2-8 years |
| Laursen et al. (138) | randomized, double-blind, placebo-controlled study | 290 infants aged 8 to 14 months | Probiotic group (N = 144 B. animalis subsp lactis and L. rhamnosus (109 CFU of each) daily + maltodextrin powde Placebo group (N = 146): maltodextrin powder |
S: up to 12 weeks before expected start in child care. E: after 6 months |
6 months | Probiotic treatment did not reduce the number of days absent from child care due to infections in healthy infants at the time of enrollment in child care | 6 months | |
| Murphy et al. (139) | Sub-Sample Analysis From a randomized, controlled, 3-arm trial (115, 116) | - Pregnant women who had at least one first-degree relative (or partner) with atopic disease, -breast feeding mothers -their infants | Two Probiotic groups: - Lactobacillus rhamnosus HN001 (N = 285 stools) - Bifidobacterium animalis subsp lactis strain HN019 (N = 50 stools) Placebo group: (N = 315 stools sample) |
Pregnant women: Lactobacillus rhamnosus HN001 (6 × 3 109 colony-forming units/d), Bifidobacterium animalis subsp lactis strain HN019 (9 × 3 109 colony-forming units/d) or placebo daily from 35 weeks gestation until 6 months if breast-feeding Infants: same treatment from day 2–16 of life to 2 years |
From 35 weeks gestation | Breast feeding mothers: for 6 months Infants: for 2 years since day 2-16 of life |
Supplementation with L. rhamnosus HN001 was associated with increased overall glycerol-3 phosphate transport capacity and enrichment of L. rhamnosus. There were no differences in development of eczema by 2 years in either community alpha or beta diversity (P > 0.05) | 2 years |
| (B) Probiotic given with hydrolyzed/ amino acid-based formulas. | ||||||||
| References | Study | Enrolled Patients | Hydrolyzed/ amino acid-based formulas+probiotic |
Probiotic Strain, Beginning of Treatment (S), End of Treatment (E). |
Pre-natal administration (if yes: duration) | Post-natal amministration (if yes: duration) | Outcomes | Follow-Up (duration) |
| Berni Canani et al. (125) | Parallel-arm randomized controlled trial | 220 children with cow's milk allergy with a median age of 5.0 months | Probiotic group (N = 110): Extensively hydrolyzed casein formula (EHCF) + Lactobacillus rhamnosus GG (LGG) Control group(N = 110): Extensively hydrolyzed casein formula (EHCF) |
Lactobacillus rhamnosus GG (LGG) S: after randomization E: 3 years |
no | 36 months | EHCF+LGG reduces the incidence of allergic manifestations (AM)(absolute risk difference was 20.23 (95% CI, 20.36 to 20.10; P <.001), and speeds up the time to development of oral tolerance in children with IgE-mediated CMA | 36 months |