We propose to characterize associations among the fecal microbiome, the fecal glycome, andmeasures of household environmental exposures in infants who do and do not subsequentlydevelop autism spectrum disorder (ASD) from the MARBLES cohort. One of the most commonco-morbidities in autism are gastrointestinal problems, and the presence of frequent symptomsof diarrhea or constipation is associated with more severe symptoms. However, virtually allresearch on GI dysfunction in ASD to date has been conducted after the ASD diagnosis hasbeen made, thus not allowing for examination of temporal relationships between GI dysbiosisand the onset of ASD. Moreover, few underlying biologic mechanisms have beenidentified. Increasingly, the prominent but insufficiently characterized, role of the microbiota inhuman health has been recognized. Environmental influences on individual gut microbiotaprofiles are also coming under scrutiny, but there has been very little work on the impact ofchemical exposures on the microbiome. Taking advantage of data and samples available froma large, prospective pregnancy study of high-risk infant siblings of children with autism, thisproject seeks to investigate the development in early postnatal life of the individual profiles ofthe gut microbiome, the environmental chemical influences on these, and their relationship to GIsymptoms and to the subsequent development of autism and its early signs. Our overarchinghypothesis is that environmental exposures common in developing countries influence thedeveloping intestinal microbiota and intestinal permeability in the first year of life and that theresultant dysbiosis and gut “leakiness” increase risk for development of ASD. With anestablished interdisciplinary team at the cutting edge of the microbiome and glycomemeasurement, we will use recently developed effective techniques to quantify fecal milk glycansand milk glycan monomers that are clear drivers for intestinal health or dysbiosis in thedeveloping infant gut microbiome. We will apply an innovative mechanistic framework thatincorporates a number of known or suspected factors in GI dysfunction in ASD, including acompromised intestinal barrier, and links exposure to environmental toxins, GI outcomes, andASD. Establishing associations between the maternal and child environment, the developinginfant gut microbiome, and onset of ASD symptomology and diagnosis would set the stage formechanistic studies examining ways to shift the infant microbiota away from onset of dysbiosisduring the first year of life—a critical developmental period—with potential implications forneurodevelopmental outcomes.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
