Probiotics and Prebiotics in Preventing Food Allergy and Eczema

Mikael Kuitunen

Curr Opin Allergy Clin Immunol. 2013;13(3):280-286.

Clinical Probiotic Studies on Prevention of Eczema and Food Allergy

The main probiotic prevention studies are summarized in Table 1 .^[20–42] In the largest cohort reported (n = 1223), supplementing pregnant women from week 36 with a mixture of four probiotics [Lactobacillus rhamnosus GG (LGG), L. rhamnosus LC705, bifidobacterium lactis Bb12 and propionibacterium] and infants receiving the same probiotics and a prebiotic oligosaccharide from birth to 6 months with 925 infants followed until age 2 years after showed a 20% reduction of eczema [32.3 to 26.0%, odds ratio (OR) 0.69 (0.52–0.93), P = 0.015] and a 30% reduction of atopic eczema [17.7 to 12.4%, OR 0.61 (0.42–0.90), P = 0.012] compared with the placebo group.^[25] Long-term follow-up until age 5 of 891 infants showed no effect in reducing eczema or any allergic disease in the whole cohort, but a significantly diminished cumulative incidence of IgE-associated eczema and food-specific IgE-sensitization in caesarean-delivered children (17% of the cohort).^[26] They showed a delayed colonization with bifidobacteria compared with vaginally delivered children, which was corrected with probiotic supplementation. A good retention of children was shown, with 88% attending at the 5-year visit. The second largest cohort from New Zealand is unique in comparison of two different probiotic strains. Pregnant women (n = 474) were treated with Lactobacillus rhamnosus HN001, bifidobacterium animalis subsp lactis HN019 or placebo 1 month prenatally and until 6 months to the breastfeeding mother and directly to infants from birth until 2 years. A 50% reduction of eczema in the lactobacillus group [26.8 vs. 14.8%, hazard ratio 0.51 (0.30–0.85)], but no change in the bifidobacteria group was found.^[32] The study highlights the importance of the bacterial strain; not every probiotic strain is efficient. The probiotic intervention was prenatal combined with postnatal both to the lactating mother and directly to the infant and with a longer intervention than in most studies. Very recently, their 4-year follow-up was reported^[33] showing sustained eczema reduction with L. rhamnosus. Interestingly, this is also the first study to show a reduction in respiratory allergies with less rhinoconjunctivitis, indicating that by preventing early onset eczema, it is possible to stop the atopic march. These two largest cohorts show an eczema preventive effect from L. rhamnosus alone or in a mixture with other strains, but not all studies do so.

Some studies used postnatal-only probiotic supplementations. In an Australian study, Lactobacillus acidophilus or placebo was administered from birth to 6 months in 231 newborns. Their long-term follow-up study until 5 years has just been published in which no significant difference in prevalences of eczema, food allergy or respiratory allergies were found^[29] consistent with earlier reported 1^[27] and 2.5 years^[28] of follow-up. Another postnatal-only study by Soh et al.[35] in Asian infants stated that infants were given Bifidobacterium longum and L. rhamnosus during 6 months in two logs lower concentrations than other studies, and they found no allergy-preventive effects. Nonhydrolyzed fermented milk with or without heat-killed Bifidobacterium breve and Streptococcus thermophilus was given from birth until 1 year and children followed at 4, 12 and 24 months. No difference in cow's milk allergy prevalence was found, but decreased positive skin prick test to cow's milk and incidence of digestive and respiratory potentially allergic events emerged.^[43] Hence, postnatal-only supplementation appears less effective in allergy prevention.

All aforementioned studies assessed allergy-preventive capacity of probiotics in high risk for allergy cohorts. Three studies used unselected cohorts. An easy-to-implement approach was used in a Swedish study,^[36] in which supplementation with Lactobacillus F19 during weaning from 4 to 13 months resulted in halved eczema frequencies at 13 months. In a Norwegian study,^[38] a probiotic mixture (LGG, L. acidophilus La-5 and Bifidobacterium animalis) given 1 month prenatally and 3 months to the breastfeeding mother showed less atopic eczema in the children at 2 years in the actively treated group [OR 0.51 (0.30–0.87)]. Supplementing the mother pre and postnatally without infant supplementation can possibly work and would be an easy way of supplementation. Boyle et al.[40] assessed whether prenatal administration without supplementing infants would suffice for allergy prevention. Using LGG from 36 weeks of gestation until delivery had no effect on eczema prevalence by age 1 year, however. A recent study evaluated the effects of maternal supplementation of L. rhamnosus LPR and B. longum BL999, Lactobacillus paracasei ST11 and BL999 or placebo 2 months before delivery and during breastfeeding from birth to 2 months. Eczema risk very efficiently decreased in both probiotic groups until 2 years [OR 0.17; 95% confidence interval (CI) 0.08–0.35, P < 0.001 and 0.16; 95% CI 0.08–0.35, P < 0.001, respectively].^[41] This study shows an effect from two combinations of bifidobacteria and lactobacilli, an unusual finding in probiotic studies. In a similar study, LGG or placebo was given to atopic mothers from the second trimester of pregnancy. After delivery, LGG was given to the breastfeeding mother or to nonbreastfeeding infants for 6 months. No effects on prevalences of allergic diseases including eczema were detected. However, the mothers' own allergic disease symptoms were relieved.^[42]

Taken together, prenatal maternal supplementation appears important for allergy-preventive effects, leading to faster infant colonization, but prenatal-only supplementation seems insufficient.^[40] Further changes in the breastmilk composition can be important for the preventive effects.^[40,44–46]

Two studies have evaluated the eczema-preventing effect of prebiotics. Moro supplemented with a galacto-oligosaccharide (GOS)/fructo-oligosaccharide (FOS) vs. maltodextrin in extensively hydrolysed formula in high-risk infants from birth to 6 months showed a significantly reduced risk of eczema at 6 months in the GOS/FOS group (9.8%; 5.4–17.1 vs. 23.1%; 16.0–32.1, P = 0.014),^[47] an effect that was sustained until 2 years.^[48] An increase in faecal bifidobacteria was evident in the GOS/FOS group.^[47] A multicentre study from five European countries randomized 830 low-risk for allergy infants to receive a regular formula with or without prebiotics before the age of 2 months. At 1 year, the prevalence of atopic dermatitis was 44% lower in the prebiotic group.^[49]

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Abstract and Introduction
Clinical Probiotic Studies on Prevention of Eczema and Food Allergy
Systematic Reviews on Probiotics for Allergy Prevention
Mechanisms of Action in Allergy Prevention
Conclusion
References
Sidebar

Table 1. Main probiotic prevention studies
Ref.	Population active, placebo	Probiotic and daily dose	Intervention prenatal	Postnatal^a	Follow-up, years	Result for eczema
Kalliomaki et al. [20]	FHA+ 159 randomized, 132 completed A=64 P=68	Lactobacillus rhamnosus GG (LGG) 2×10¹⁰	1 month	6 months to BF mother or infant if not BF (56%)	2	RR of eczema 0.51 (0.32–0.84) in probiotic vs. placebo
Kalliomaki et al.^b [21]	107 completed A=53 P=54				4	RR of eczema 0.57 (0.33–0.97)
Kalliomaki et al.^b [22]	116 completed A=53 P=62				7	RR of eczema 0.64 (0.45–0.92)
Rautava et al. [23]	FHA+ 62 randomized, 57 completed A=27, P=30	LGG 2×10¹⁰	2–4 weeks	3 months BF mother only	2	RR of eczema 0.32 (0.12–0.85)
Rautava et al [24]	FHA+ 81 randomized, 72 completed A=32, P=40	LGG 1×10¹⁰, B. lactis Bb12 1×10¹⁰	No	From start of infant formula to 12 months	1	NS eczema decrease 20 to 13% in placebo vs. probiotic group
Kukkonen et al. [25]	FHA+ 1223 randomized, 925, completed A=461 P=464	LGG: 5×10⁹, L. rhamnosus LC705: 5×10⁹, B breve Bb99 : 2×10⁸, propionibactfreund: 2×10⁹ mothers 2 × dose	1 month	6 months	2	OR of eczema 0.69 (0.52–0.93) and of IgE+eczema 0.61 (0.42–0.90)
Kuitunen^c et al. [26]	891 completed A=445 P=446				5	No difference in eczema in whole cohort; OR 0.43 (0.19–0.95) in probiotic caesarean delivered
Taylor et al. [27]	FHA+ 226 randomized, 178 completed A=89 P=89	L. acidophilus 3×10⁹	No	6 months	1	No eczema difference between groups; more IgE+ eczema in probiotic group (26 vs. 14%), P=0.045
Prescott^d et al. [28]	153 completed A=77, P=76				2.5	No eczema difference between groups
Jensen^d et al. [29•]	123 completed (54%) A=66, P=57				5	No eczema difference between groups
Abrahamsson et al. [30]	FHA+ 232 randomized, 188 completed A=95 P=93	L. reuteri 1×10⁸	1mo	12 months	2	Eczema no difference, less IgE+ eczema 2nd year in probiotic group (8 vs. 20%), P=0.02
Kopp et al. [31]	FHA+ 105 randomized, 94 completed A=50 P=44	LGG 1×10¹⁰	1 month	0–3 months BF mother only, 3–6 months direct to infant	2	No eczema difference between groups
Wickens et al. [32]	FHA+ 512 randomized, 446 completed A1=144 A2=152 P=150	L. rhamnosus HN001 6×10⁹, B. animalis HN019 9×10⁹	1 month	Until 6 months if BF + direct to infants 2 years	2	HR 0.51 (.30–.85) of eczema in lactobacillus group; no difference to placebo in bifidogroup
Wickens^e et al. [33•]	425 completed A1=136, A2=146, P=143				4	HR 0.57 (0.39–0.83) of eczema in lactobacillus group; no difference to placebo in bifido group
Huurre et al. [34]	Unselected 171 randomized, 140 completed A=72 P=68	LGG 1×10¹⁰, BifidoBb12 1×10¹⁰	From 1st trimester	End of BF to mother only	1	No significant eczema difference between groups
Soh et al. [35]	FHA+ 253 randomized, 245 completed A=124 P=121	B. longum BL999 & L. rhamnous LPR sum 2.8×10⁸	No	6 months	1	No significant eczema difference between groups
West et al. [36]	Unselected 179 randomized, 171 completed A=84 P=87	Lactobacillus F19 1×10⁸	No	Age 4–13 months in cereals	1	Eczema lower in probiotic 11% vs. placebo 22%, P<0.05
Niers et al. [37]	FHA+ 156 randomized, 98 completed A=50 P=48	B. bifidum W23 1×10⁹, B. lactis W52 1×10⁹, Lc. lactis W58 1×10⁹	1 month	12 months	2	Parent reported eczema lower at 3 mo, later no difference between groups
Dotterud et al. [38]	Unselected 415 randomized, 278 completed A=138 P=140	LGG 5×10¹⁰, L. acidopLa–5 5×10¹⁰, Bifido Bb–12 5×10⁹	1 month	3 months to BF mother only	2	OR of eczema 0.51 (0.30–0.87) in probiotic group vs. placebo
Kim et al. [39]	FHA+ 112 randomized, 68 completed A=33 P=35	B. bifidum BGN4 1.6×10⁹, B. lactis AD011 1.6×10⁹, L. acidoph 1.6×10⁹	1–2 months	3 months to BF mother, then age 4–6 months to infant	1	Less eczema in probiotic 36% vs. placebo 62%, P=0.029
Boyle et al. [40]	FHA+ 250 randomized, 210 completed A=108 P=102	LGG 1.8×10⁸	1 month	No	1	No significant eczema difference between groups
Rautava et al. [41]	FHA+ 241 randomized, 205 completed A1=62, A2=73, P=70	A1: L. rhamnosus LPR+ B. longum BL999, A2: L. paracasei ST11+ BL999, 1×10⁹ each	2	2 months BF mother	2	OR of eczema 0.17 (0.08–0.35) in A1 and 0.16 (0.08–0.35) in A2
Ou et al. [42]	FHA+ 191 randomized, 128 completed A=65, P=63	LGG 1×10¹⁰	From 2^nd trimester	6 months BF mother or non-BF infant	3	No significant eczema difference between groups

FHA, family history of atopy positive; HR, hazard ratio; OR, odds ratio; RR, relative risk.
^aProbiotic directly to the child, if not otherwise specified.
^bSame cohort as Kalliomäki 2001 ref [20].
^cSame cohort as Kukkonen 2007 ref [25].
^dSame cohort as Taylor 2007 ref [27].
^eSame cohort as Wickens 2008 ref [32].