Environmental Influence on Infant Microbiome Development and ASD Symptoms

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ABSTRACT We propose to characterize associations among the fecal microbiome, the fecal glycome, and measures of household environmental exposures in infants who do and do not subsequently develop autism spectrum disorder (ASD) from the MARBLES cohort. One of the most common co-morbidities in autism are gastrointestinal problems, and the presence of frequent symptoms of diarrhea or constipation is associated with more severe symptoms. However, virtually all research on GI dysfunction in ASD to date has been conducted after the ASD diagnosis has been made, thus not allowing for examination of temporal relationships between GI dysbiosis and the onset of ASD. Moreover, few underlying biologic mechanisms have been identified. Increasingly, the prominent but insufficiently characterized, role of the microbiota in human health has been recognized. Environmental influences on individual gut microbiota profiles are also coming under scrutiny, but there has been very little work on the impact of chemical exposures on the microbiome. Taking advantage of data and samples available from a large, prospective pregnancy study of high-risk infant siblings of children with autism, this project seeks to investigate the development in early postnatal life of the individual profiles of the gut microbiome, the environmental chemical influences on these, and their relationship to GI symptoms and to the subsequent development of autism and its early signs. Our overarching hypothesis is that environmental exposures common in developing countries influence the developing intestinal microbiota and intestinal permeability in the first year of life and that the resultant dysbiosis and gut “leakiness” increase risk for development of ASD. With an established interdisciplinary team at the cutting edge of the microbiome and glycome measurement, we will use recently developed effective techniques to quantify fecal milk glycans and milk glycan monomers that are clear drivers for intestinal health or dysbiosis in the developing infant gut microbiome. We will apply an innovative mechanistic framework that incorporates a number of known or suspected factors in GI dysfunction in ASD, including a compromised intestinal barrier, and links exposure to environmental toxins, GI outcomes, and ASD. Establishing associations between the maternal and child environment, the developing infant gut microbiome, and onset of ASD symptomology and diagnosis would set the stage for mechanistic studies examining ways to shift the infant microbiota away from onset of dysbiosis during the first year of life—a critical developmental period—with potential implications for neurodevelopmental outcomes.