Lifestyle and allergy : in relation to viral infections and gut microbiota

Sammanfattning: Allergy-related diseases such as food allergy, eczema, asthma and rhinoconjunctivitis affect nearly half of Swedish children before twelve years of age and are more prevalent in populations with westernized lifestyle. Reduced microbial exposure very early in life is believed to play a crucial role for this increased risk. Children of families with an anthroposophic lifestyle are less commonly affected. The aim of this thesis was to study associations between this lifestyle and development of allergy-related disease and the possible role of microbial exposure in the form of herpesviruses and gut microbiota. All four papers in this thesis are based on the prospective birth cohort study ALADDIN (Assessment of Lifestyle and Allergic Disease during INfancy) in which children with anthroposophic and non-anthroposophic lifestyles have been followed up with questionnaires, examinations, parental interviews and blood- and fecal samples. In paper I we determined IgG-levels towards Epstein-Barr virus, HHV6, HHV7 and cytomegalovirus in blood samples from 62 anthroposophic and 95 non-anthroposophic children at one and two years of age and from their parents. Seroprevalence of these herpesviruses was similar in the lifestyle groups among both children and parents and is therefore unlikely to explain the reduced risk of sensitization among anthroposophic children. In paper II we analyzed the bacterial composition in fecal samples from 55 anthroposophic and 73 non-anthroposophic infants at six days, three weeks, two months and six months of age and from their mothers, using pyrosequencing of 16S rRNA genes. Mode of delivery and breastfeeding were stronger determinants of the infant gut microbiota than anthroposophic lifestyle. At six months anthroposophic lifestyle was associated with higher abundance of Bifidobacterium and lower abundance of Bacteroides. No associations with anthroposophic lifestyle were seen up to two months of age or in the mothers. Global microbiota diversity was not influenced by anthroposophic lifestyle and is therefore unlikely to mediate the risk-reducing effect on sensitization. Further studies, with higher taxonomic resolution and deeper coverage, could better clarify a potential role of gut microbiota. In paper III we investigated the effect of lifestyle on the risk of clinical allergy-related manifestations up to two years of age in 116 anthroposophic, 212 partly anthroposophic and 162 non-anthroposophic children. Risk of food hypersensitivity and recurrent wheeze, but not eczema, was reduced among children with anthropsophic and partly anthroposophic lifestyle. Delayed wash of the newborn’s whole body was associated with reduced risk of food hypersensitivity, eczema and sensitization whereas recurrent wheeze was associated with maternal level of education and child having had milk formula during the first week of life. The ‘anthroposophic effect’ however remains largely unexplained. In paper IV we described incidence and prevalence of sensitization to food, animal and pollen allergens up to five years of age for 100 anthroposophic, 209 partly anthroposophic and 165 non-anthroposophic children. The effect of lifestyle on food sensitization differed significantly with age of the child. The reduced prevalence of sensitization among children from families with an anthroposophic lifestyle was mainly explained by a low risk of food allergen sensitization before one year of age. In conclusion, this thesis illustrates the strong influence of very early lifestyle exposures on allergy-related outcomes, but also the complexity of studying lifestyle in relation to disease. The convincing findings of association between anthroposophic lifestyle and allergy-related outcomes make the ALADDIN cohort a ‘model’ for studying how lifestyle affects the development of allergy, regardless of what the ‘anthroposophic factor’ might be.