Prenatal alcohol effects on the gut microbiome contributing to failure to thrive and altered immune function

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Fetal Alcohol Spectrum Disorder (FASD) can include growth deficiency that is not attributable to parental height, gestational age, or poor nutrition. Recent studies on the gut microbiome indicate that perturbations in the population dynamics of the gut bacteria early in life can have deleterious consequences on the host including failure to thrive and other sequelae typically associated with poor nutrition throughout life. The impact of an altered microbiota can negate efforts to overcome these deficiencies with improved nutrition. Alcohol consumption has been demonstrated to alter the ratios of defined bacterial genera in adults. Since newborn babies adopt the flora of the birth mother, it is likely that neonates at high risk for a FASD have an altered gut microbiome that ultimately translates to poor nutrition given the importance of gut bacteria in processing certain food products and generating dietary needs. Gut bacteria also play a crucial role in promoting immunologic homeostasis. Alterations in bacterial populations may result in less down-regulatory IL-25 production by epithelial cells and increased proinflammatory T cells. The role of the gut microbiome in FASD associated immunological based diseases and failure to thrive has been understudied. We hypothesize newborn rats exposed to alcohol in utero will develop altered gut microbiota upon delivery compared to control rat pups and that this altered microbiota will contribute to delayed growth and immune dysregulation. To test this hypothesis we propose to 1) Compare the gut microbiota of female rats before and after chronic consumption of alcohol, and analyze the gut microbiota of their pups over time to determine if they adopt the flora of the mother. Additionally, we will determine if the flora is distinct from that of pups born to control dams not receiving alcohol. 2) Compare the intestinal immune features from pups exposed to alcohol in utero to control pups to determine if alcohol exposure results in reduced regulatory immune system elements and an increase in proinflammatory markers and T cells. 3) Identify bacterial profiles in the gut microbiota associated with failure to thrive and/or immune dysregulation and determine if these conditions can be treated by therapeutic application of probiotics designed to match the colonic flora of pups born to control dams. Future studies could readily be applied to human subjects if these studies in animals provide a sound premise for clinical investigation.