Infant gut microbiota and allergy development in children from farming families - the FARMFLORA cohort

Abstract

Allergies have increased in industrialized countries, including Sweden, especially in the 1970´s to 1990´s. An increasingly hygienic lifestyle with less exposure to bacteria and other microbes has been suggested as a contributing factor, based e.g. on epidemiological studies linking factors associated with increased microbial exposure, like farm living, older siblings or pets, to protection from later allergy. Microbial exposure in early life may stimulate the developing immune system in a way that promotes the maturation of tolerance mechanisms that prevent allergy. The gut microbiota is an important stimulus for the immune system, and its composition and development may have implications for later allergy. Here, we followed the gut colonization pattern by quantitative culture of fecal samples obtained over the first 18 months of life in the FARMFLORA birth cohort, consisting of children living on small dairy farms or in the same rural area but not on farms, in Southwest Sweden. Major facultative and anaerobic bacteria were identified, and we also studied the lactobacillus flora in more detail. The maturation of the gut microbiota was mirrored in an increasing ratio of anaerobic to facultative bacterial counts with increasing age. Colonization patterns were related to farm living, pet exposure, siblings and other exposures, and to allergy at 3 or 8 years of age. A farming environment was associated with an increased ratio of anaerobic to facultative bacteria in feces at 1 week of age and lower number of E. coli, indicating early acquisition of anaerobes able to suppress facultative bacteria. Farmers’ infants also harbored Clostridioides difficile less frequently by 1 year of age, indicating a more mature gut microbiota able to suppress this bacterium. Contact with household pets was associated with more frequent colonization by several anaerobic bacteria early in life. Being firstborn, delivered by cesarian section or exposed to antibiotics during delivery were associated with delayed colonization by typical fecal bacteria, higher numbers of facultative bacteria in the early gut microbiota, and less colonization by certain species of lactobacilli. Firstborn infants showed signs of delayed gut microbiota maturation, with increased colonization by C. difficile and a low ratio of anaerobic to facultative bacterial counts in the gut microbiota by one year of age. Allergy was negatively associated with a high ratio of anaerobic to facultative bacteria in feces and colonization by anaerobic bacteria early in life, and with several species of lactobacilli. Colonization by C. difficile was instead associated with an increased risk of allergy. Taken together, our findings suggest that farm living and household pets, but also older siblings have an impact on the early gut microbiota. The effects of these exposures on the gut microbiota may contribute to their protective effect against allergy development, but further studies are needed to confirm the observations made in this small birth cohort study.