Childhood allergy is preceded by an absence of gut lactobacilli species and higher levels of atopy-related plasma chemokines

Abstract

Alterations in the composition and reduced diversity of the infant microbiome are associated with allergic disease in children. Further, an altered microbiota is linked to immune dysregulation, including skewing of different T helper (Th) subsets, which is also seen in atopic individuals. The aim of this study was, therefore, to investigate the associations between gut lactobacilli and Th-related plasma factors in allergy development during childhood. A total of 194 children with known allergy status at 1 year of age were followed to 10 years of age. We used real-time polymerase chain reaction (PCR) to investigate the presence of three lactobacilli species (Lactobacillus casei, L. paracasei, L. rhamnosus) in infant fecal samples (collected between 1 week and 2 months of age) from a subgroup of children. Plasma chemokines and cytokines were quantified at 6 months and at 1, 2, 5 and 10 years of age with Luminex or enzyme-linked immunosorbent assay (ELISA). Fractional exhaled nitrogen oxide (FeNO) was measured and spirometry performed at 10 years of age. The data were analysed by non-parametric testing and a logistic regression model adjusted for parental allergy. An absence of these lactobacilli and higher levels of the chemokines BCA-1/CXCL13, CCL17/TARC, MIP-3α/CCL20 and MDC/CCL22 in plasma at 6 months of age preceded allergy development. The presence of lactobacilli associated with lower levels of atopy-related chemokines during infancy, together with higher levels of interferon (IFN)-γ and lower FeNO during later childhood. The results indicate that the presence of certain lactobacilli species in the infant gut may influence allergy-related parameters in the peripheral immune system, and thereby contribute to allergy protection.

Keywords: allergy; chemokines; child; gut lactobacillus; infant; microbiota; plasma.

Conflict of interest statement

The authors have no conflicts of interest to declare.

© The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

Figures

Fig. 1

The presence of lactobacilli was evaluated in feces collected at four time‐points during infancy (1 and 2 weeks, 1 and 2 months of age). (a) The proportions of allergic and non‐allergic children at 1, 2, 5 or 10 years of age within the groups where lactobacilli were detected at one or more time‐points or were non‐detectable at all time‐points. (b) The proportions of allergic and non‐allergic children at 1, 2, 5 or 10 years of age within the groups where lactobacilli were detected at three to four time‐points, one to two time‐points or were non‐detectable at all time‐points. (c) The proportions of children that were consistently allergic or non‐allergic at 1, 2, 5 and 10 years of age within the groups where lactobacilli were detected at one or more time‐points or were non‐detectable at all time‐points (left), or detected at three to four time‐points, one to two time‐points or were non‐detectable at all time‐points (right). (d) The proportions of children where lactobacilli were detected at one or more time‐points or were non‐detectable at all time‐points within the groups with two allergic parents (double heredity) or two non‐allergic parents (no heredity). (e) The same as in (b), including only 1‐ and 2‐year‐old children with double heredity. Fisher’s exact test (a,c,d) or c2 test (b,c,e) were used for statistical analysis.

Fig. 2

The levels (pg/ml) of BCA‐1/CXCL13 (a), TARC/CCL17 (b), MIP‐3α/CCL20 (c) and MDC/CCL22 (d) in plasma obtained at 6 months of age in relation to allergic disease at 1 year of age (left column) or 10 years of age (middle column), or in relation to being consistently non‐allergic at 1, 2, 5 and 10 years of age, allergic at 5 and 10 years of age or being consistently allergic at 1, 2, 5 and 10 years of age (right column). The Mann–Whitney U‐test was used for statistical analysis.

Fig. 3

(a) The levels (pg/ml) of BCA‐1/CXCL13, MIP‐3α/CCL20 and MDC/CCL22 in plasma obtained at 6 months of age from the groups where lactobacilli were detected at three to four time‐points, one to two time‐points or were non‐detectable at all time‐points. (b) Same as in (a), including only children with double heredity. (c) The same as in (a), including only non‐allergic children. (d) Heredity and levels (pg/ml) of BCA‐1/CXCL13, MIP‐3α/CCL20 and MDC/CCL22 in plasma obtained at 6 months of age from the group with available lactobacilli data. The Mann–Whitney U‐test was used for statistical analysis.

Fig. 4

(a) The levels (pg/ml) of interferon (IFN)‐γ in plasma obtained at 5 years age from the groups where lactobacilli were detected at one or more time‐points or were non‐detectable at all time‐points (left) or in the groups where lactobacilli were detected at three to four time‐points, one to two time‐points or were non‐detectable at all time‐points (right). (b) Heredity and levels (pg/ml) of IFN‐γ in plasma obtained at 5 years age from the group with available lactobacilli data. (c) The levels of fractional exhaled nitric oxide (FeNO) at 10 years of age in the groups where lactobacilli were detected at one or more time‐points or were non‐detectable at all time‐points (left) or in the groups where lactobacilli were detected at three to four time‐points, one to two time‐points or were non‐detectable at all time‐points (right). (d) Same as in (c), including only children with double heredity. (e) Same as in (c), including only non‐allergic children. The Mann–Whitney U‐test was used for statistical analysis.

Fig. 5

Detection of lactobacilli (L. casei, L. paracasei and L. rhamnosus) in feces during the first 2 months of life associates with reduced allergy prevalence and lower levels of atopy‐related chemokines in the first year(s) of life, and higher levels of interferon (IFN)‐γ and lower fractional exhaled nitric oxide (FeNO) later in childhood. Graphic design: Fuad Bahram, FB Scientific Art Design.