Children growing up on farms have low rates of allergy, but the mechanism for this protective effect has not been fully elucidated. Short chain fatty acids (SCFAs) produced by the gut microbiota may play a role in protection from allergy. We measured fecal SCFA levels in samples collected from 28 farming and 37 control children over the first 3 years of life using gas chromatography. Data on diet and other host factors were recorded and allergy was diagnosed at 8 years of age. Among all children, median propionic and butyric acid concentration increased over the first 3 years, and longer SCFAs typically appeared by 1 year of age. Farm children had higher levels of iso-butyric, iso-valeric and valeric acid at 3 years of age than rural controls. In addition, children with elder siblings had higher levels of valeric acid at 3 years of age, and dietary factors also affected SCFA pattern. High levels of valeric acid at 3 years of age were associated with low rate of eczema at 8 years of age. The fecal SCFA pattern in farm children suggests a more rapid maturation of the gut microbiota. Valeric acid or associated microbes may have protective potential against eczema.

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<b><i>Background:</i></b> Short-chain fatty acids (SCFAs) are abundant bacterial metabolites in the gut, with immunomodulatory properties. Hence, they may influence allergy development. Previous studies have linked fecal SCFA pattern during infancy with allergy. However, the association of SCFAs to allergic outcomes in adolescence is not well established. Here, we examined how the fecal SCFA pattern at 1 year of age related to allergy at 13 years of age. <b><i>Methods:</i></b> Levels of 8 SCFAs in fecal samples collected at 1 year of age from 110 children were quantified using gas chromatography. The same individuals were evaluated at 13 years of age for allergic symptoms, allergy diagnosis and allergy medication by questionnaire, and for sensitization using skin prick test against egg, milk, fish, wheat and soy, cat, dog, horse, birch, and timothy grass. <b><i>Results:</i></b> The concentration of fecal valeric acid at 1 year of age was inversely associated with eczema at 13 years of age (OR 0.6, 95% CI: 0.4–1.0, <i>p</i> = 0.049) and showed a trend for inverse association with food allergy at 13 years of age (OR 0.6, 95% CI: 0.4–1.0, <i>p</i> = 0.057). In a sub-group analysis of children with eczema at 1 year of age, a higher concentration of fecal valeric acid was linked with reduced risk of their eczema remaining at 13 years of age (OR 0.2, 95% CI: 0.0–1.5), although this latter analysis did not reach statistical significance (<i>p</i> = 0.12). <b><i>Conclusions:</i></b> Our findings lend further support to the notion of early childhood as a critical period when allergy may be programmed via the gut microbiota. Higher levels of fecal valeric acid may be characteristic of a protective gut microbiota and/or actively contribute to protection from eczema and food allergy.

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