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      Infant gut microbiota and the hygiene hypothesis of allergic disease: impact of household pets and siblings on microbiota composition and diversity

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          Abstract

          Background

          Multiple studies have demonstrated that early-life exposure to pets or siblings affords protection against allergic disease; these associations are commonly attributed to the “hygiene hypothesis”. Recently, low diversity of the infant gut microbiota has also been linked to allergic disease. In this study, we characterize the infant gut microbiota in relation to pets and siblings.

          Methods

          The study population comprised a small sub-sample of 24 healthy, full term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mothers reported on household pets and siblings. Fecal samples were collected at 4 months of age, and microbiota composition was characterized by high-throughput signature gene sequencing.

          Results

          Microbiota richness and diversity tended to be increased in infants living with pets, whereas these measures were decreased in infants with older siblings. Infants living with pets exhibited under-representation of Bifidobacteriaceae and over-representation of Peptostreptococcaceae; infants with older siblings exhibited under-representation of Peptostreptococcaceae.

          Conclusions

          This study provides new evidence that exposure to pets and siblings may influence the early development of the gut microbiota, with potential implications for allergic disease. These two traditionally protective “hygiene hypothesis” factors appear to differentially impact gut microbiota composition and diversity, calling into question the clinical significance of these measures. Further research is required to confirm and expand these findings.

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          Most cited references39

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          Low diversity of the gut microbiota in infants with atopic eczema.

          It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P = .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P = .02 and P = .01) and the phylum Proteobacteria at 12 months of age (P = .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R [edgeR] test: P = .008, q = 0.02). Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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            Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age.

            Changes in the human microbiome have been suggested as a risk factor for a number of lifestyle-related disorders, such as atopic diseases, possibly through a modifying influence on immune maturation in infancy. We aimed to explore the association between neonatal fecal flora and the development of atopic disorders until age 6 years, hypothesizing that the diversity of the intestinal microbiota influences disease development. We studied the intestinal microbiota in infants in the Copenhagen Prospective Study on Asthma in Childhood, a clinical study of a birth cohort of 411 high-risk children followed for 6 years by clinical assessments at 6-month intervals, as well as at acute symptom exacerbations. Bacterial flora was analyzed at 1 and 12 months of age by using molecular techniques based on 16S rRNA PCR combined with denaturing gradient gel electrophoresis, as well as conventional culturing. The main outcome measures were the development of allergic sensitization (skin test and specific serum IgE), allergic rhinitis, peripheral blood eosinophil counts, asthma, and atopic dermatitis during the first 6 years of life. We found that bacterial diversity in the early intestinal flora 1 and 12 months after birth was inversely associated with the risk of allergic sensitization (serum specific IgE P = .003; skin prick test P = .017), peripheral blood eosinophils (P = .034), and allergic rhinitis (P = .007). There was no association with the development of asthma or atopic dermatitis. Reduced bacterial diversity of the infant's intestinal flora was associated with increased risk of allergic sensitization, allergic rhinitis, and peripheral blood eosinophilia, but not asthma or atopic dermatitis, in the first 6 years of life. These results support the general hypothesis that an imbalance in the intestinal microbiome is influencing the development of lifestyle-related disorders, such as allergic disease. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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              Diversity of Bifidobacteria within the Infant Gut Microbiota

              Background The human gastrointestinal tract (GIT) represents one of the most densely populated microbial ecosystems studied to date. Although this microbial consortium has been recognized to have a crucial impact on human health, its precise composition is still subject to intense investigation. Among the GIT microbiota, bifidobacteria represent an important commensal group, being among the first microbial colonizers of the gut. However, the prevalence and diversity of members of the genus Bifidobacterium in the infant intestinal microbiota has not yet been fully characterized, while some inconsistencies exist in literature regarding the abundance of this genus. Methods/Principal Findings In the current report, we assessed the complexity of the infant intestinal bifidobacterial population by analysis of pyrosequencing data of PCR amplicons derived from two hypervariable regions of the 16 S rRNA gene. Eleven faecal samples were collected from healthy infants of different geographical origins (Italy, Spain or Ireland), feeding type (breast milk or formula) and mode of delivery (vaginal or caesarean delivery), while in four cases, faecal samples of corresponding mothers were also analyzed. Conclusions In contrast to several previously published culture-independent studies, our analysis revealed a predominance of bifidobacteria in the infant gut as well as a profile of co-occurrence of bifidobacterial species in the infant’s intestine.
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                Author and article information

                Journal
                Allergy Asthma Clin Immunol
                Allergy Asthma Clin Immunol
                Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology
                BioMed Central
                1710-1484
                1710-1492
                2013
                22 April 2013
                : 9
                : 1
                : 15
                Affiliations
                [1 ]Department of Pediatrics, University of Alberta, 3-527 Edmonton Clinic Health Academy 11405 – 87th Avenue, Edmonton, AB, T6G IC9, Canada
                [2 ]Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
                [3 ]Cell & Systems Biology, University of Toronto, Toronto, ON, Canada
                [4 ]Agriculture, Food & Nutritional Sciences, University of Alberta, Edmonton, AB, Canada
                [5 ]Department of Medicine, McMaster University, Hamilton, ON, Canada
                [6 ]Pediatrics & Child Health, University of Manitoba, Winnipeg, MB, Canada
                [7 ]Manitoba Institute of Child Health, Winnipeg, Canada
                Author notes
                CHILD Study Investigators
                Article
                1710-1492-9-15
                10.1186/1710-1492-9-15
                3655107
                23607879
                e079e856-0beb-41ef-ad55-2670ddc223de
                Copyright ©2013 Azad et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 November 2012
                : 7 March 2013
                Categories
                Research

                Immunology
                infants,gut microbiota,gut microbiome,hygiene hypothesis,microflora hypothesis,pets,siblings,atopy,allergic disease,environmental exposures

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