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Development of allergy, salivary IgA antibodies and gut microbiota in a Swedish birth cohort
Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The increasing prevalence of allergic diseases in affluent societies has been associated with changes in microbial exposure early in life and a less diverse gut flora. The objective of this thesis was to assess the development of allergic sensitisation and symptoms during the first four years of life in a non-selected birth cohort in relation to environmental factors, family history, gut microbiota and salivary IgA antibodies. The cohort comprised all 1,228 infants living in a Swedish county who were born over a one-year period. The parents replied to questionnaires, and 817 children (67 %) were skin prick tested both at 1 and 4 years of age. Saliva (n=279), faecal (n=139) and blood (n=253) samples were collected at 1 year of age from children with a positive skin prick test at 1 year and from a sample of children with a negative skin prick test. Faecal samples were also obtained from 53 children at 4 years of age.

Dog keeping during infancy was associated with a decreased risk of sensitisation to pollen and late-onset wheezing at age 4, and the reduced odds ratios persisted after adjustment for heredity and avoidance measures, OR 0.3, 95% CI 0.1-0.9 and OR 0.5, 95% CI 0.2-1.0, respectively. In contrast, early dog keeping was associated with an increased risk of earlyonset transient wheezing but only in children with parental asthma (OR 2,8, 95% CI 1.3-6.4).

Levels of short chain fatty acids (SCFAs) in faeces were assessed both at 1 and 4 years of age and related to the development of sensitisation and symptoms. The levels of acetic (p<.01) and propionic (p<.01) acids decreased from one to four years of age, whereas valeric acid (p<.001) increased which is in line with a more complex gut microbiota with age. Allergic children, compared with non-allergic children, had lower levels of i-butyric, i-valeric and valeric acid in faeces both at 1 and 4 years of age.

Low levels of secretory IgA (SIgA) in saliva were associated with wheezing but only in sensitised children. In children with positive SPT to at least one allergen both at 1 and 4 years of age and in children with circulating IgE antibodies to egg or cat at one year of age, those who developed late-onset wheezing had lower levels of SIgA than those who did not, p=.04 and p=.02 respectively. Of 9 children with levels of SIgA in the upper quartile and persistent sensitisation, none developed wheezing, compared with 10/20 children with lower levels, (p=. 01). Having older siblings, more than three infections during infancy, at least one smoking parent and male gender were all associated with high levels (in the upper quartile) of total IgA and SIgA.

The findings in this thesis indicate that the microbial load early in life could affect the development of allergy. A functional assessment of the gut flora demonstrated differences between allergic and non-allergic children both at 1 and 4 years of age. Salivary IgA was associated with infections during infancy, and high levels of secretory IgA protected from symptoms in sensitised children. Finally, dog keeping in infancy may offer protection from allergy, but the mechanism is uncertain.

Place, publisher, year, edition, pages
2008. , 65 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1179
Keyword [en]
pet keeping, sensitisation, intestinal microflora, short chain fatty acids, allergy, salivary IgA, late-onset wheezing
Research subject
Pediatrics
Identifiers
URN: urn:nbn:se:umu:diva-1627ISBN: 978-91-7264-517-2 (print)OAI: oai:DiVA.org:umu-1627DiVA: diva2:141595
Public defence
2008-05-16, Sal 260, plan 2, 3A, NUS, Umeå, 09:00 (English)
Opponent
Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2010-01-18Bibliographically approved
List of papers
1. Development of atopy and wheezing symptoms in relation to heredity and early pet keeping in a Swedish birth cohort
Open this publication in new window or tab >>Development of atopy and wheezing symptoms in relation to heredity and early pet keeping in a Swedish birth cohort
2004 (English)In: Pediatric allergy and immunology, Vol. 15, no 4, 316-22 p.Article in journal (Refereed) Published
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-3116 (URN)
Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2011-11-06Bibliographically approved
2. Microflora-associated characteristics in faeces from allergic and nonallergic infants
Open this publication in new window or tab >>Microflora-associated characteristics in faeces from allergic and nonallergic infants
Show others...
2000 (English)In: Clinical and experimental allergy, Vol. 30, no 11, 1591-1596 p.Article in journal (Refereed) Published
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-3117 (URN)
Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2011-11-06Bibliographically approved
3. Faecal short chain fatty acid pattern and allergy in early childhood
Open this publication in new window or tab >>Faecal short chain fatty acid pattern and allergy in early childhood
2009 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, no 5, 823-827 p.Article in journal (Refereed) Published
Abstract [en]

Aim: To investigate whether functional changes of the gut flora over time were related to sensitization and allergic symptoms at four years of age.

Methods: The levels of short chain fatty acids (SCFAs) in faecal samples at one (n = 139) and four (n = 53) years of age were related to the development of positive skin prick tests (SPT) and allergic symptoms during the first four years of life.

Results: Faecal acetic (p < 0.01) and propionic (p < 0.01) acids decreased from one to four years of age, while valeric acid (p < 0.001) increased. Low levels of i-butyric (p = 0.01), i-valeric (p = 0.03) and valeric acids (p = 0.02) at one year were associated with questionnaire-reported symptoms of food allergy at four years. Positive SPTs and allergic symptoms at four years were associated with low faecal levels of i-butyric, i-valeric and valeric acids. At one year of age, infants with, as compared to without older siblings had higher median levels of valeric acid.

Conclusion: A slow functional maturation of the gut microflora, as measured by faecal levels of SCFAs is associated with allergy both at one and four years. The findings lend further support to an association between allergy and the development of microbial diversity.

Keyword
Allergic children; Intestinal flora; Short chain fatty acids; Sensitization
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-3118 (URN)10.1111/j.1651-2227.2008.01215.x (DOI)
Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2011-11-06Bibliographically approved
4. High salivary secretory IgA antibody levels are associated with less late-onset wheezing in IgE-sensitized infants
Open this publication in new window or tab >>High salivary secretory IgA antibody levels are associated with less late-onset wheezing in IgE-sensitized infants
Show others...
2011 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 22, no 5, 477-481 p.Article in journal (Refereed) Published
Abstract [en]

Low levels of secretory IgA (SIgA) and transient IgA deficiency have been associated with an increased risk for allergy, but data are conflicting. The aim was to assess the relationship between salivary SIgA antibody levels at 1 yr and wheezing at age four in a birth cohort, in particular the possible protective role of salivary SIgA in sensitized children. Saliva samples were obtained from all children (n = 67) with a positive skin prick test (SPT) at 1 yr and 212 children with a negative SPT. In all, 200 of these children responded to questionnaires at 4 yrs and 183 were skin prick tested at that age. The levels of salivary SIgA and salivary IgA antibodies to the most common food allergen egg and inhalant allergen cat were analyzed by ELISA. Serum was analyzed for IgE antibodies to egg and cat. Development of late-onset wheezing was associated with low SIgA levels in children with positive SPT to at least one allergen both at 1 and 4 yrs of age (p = 0.04), as well as in children with circulating IgE antibodies to egg or cat at 1 yr (p = 0.02). None of nine persistently sensitized children with SIgA levels in the upper quartile developed wheezing, when compared to 10/20 children with lower levels (p = 0.01). Older siblings, more than three infections during infancy, at least one smoking parent, and male gender, were all associated with SIgA in the upper quartile. In conclusion, high levels of SIgA antibodies in sensitized infants were associated with significantly less late-onset wheezing, supporting a protective role against development of asthmatic symptoms. Recurrent infections and other factors supporting an increased microbial pressure during infancy were associated with high levels of salivary SIgA.

Place, publisher, year, edition, pages
Copenhagen: Munksgaard International Publ., 2011
Keyword
secretory IgA; saliva; sensitization; late-onset wheezing; children
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-3119 (URN)10.1111/j.1399-3038.2010.01106.x (DOI)
Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2011-11-10Bibliographically approved

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