Tryp-to-Brain

Growing awareness suggests the gut microbiome contributes to gastrointestinal and behavioral symptoms of autism spectrum disorder (ASD). The mechanisms by which gut microbiota influence ASD symptoms are unclear. Tryptophan (Trp), an essential amino acid absorbed and metabolized in the GI tract, is the sole substrate for serotonin synthesis, occurring primarily in the gut (90%) and the central nervous system (10%). Altered Trp metabolite concentrations are linked to neurological disorders, including ASD, with studies noting Trp deficiency in autistic patients. Hyperserotonemia is a biomarker for ASD, traditionally studied in the CNS, although 5-HT is primarily produced from Trp in the GI tract. Research suggests ASD pathogenesis may begin in fetal life, influenced by maternal nutrition during pregnancy. We hypothesize that prenatal diet impacts brain development and ASD risk. Our goal is to understand how prenatal Trp availability affects offspring cognition, neural systems (serotonergic, GABAergic, glutamatergic), GI functions, and microbiota using an Nf1+/- mouse model of ASD. Pregnant Nf1+/- and wild-type mice will receive a diet enhanced in Trp (TRP+, 1.5%), or a control diet (0.7%) from embryonic day 1 to weaning. Offspring will undergo behavior analyses and molecular approaches. This longitudinal study will use the same animals to correlate behavior, neurophysiology, GI, and microbiome changes. Understanding the impact of prenatal Trp availability on ASD can inform dietary guidelines for pregnant women, potentially reducing ASD risk. This research could lead to early interventions that improve the quality of life for individuals with ASD and their families, fostering greater societal inclusion and support. 

prenatal diet | tryptophan | gut-brain axis | autism spectrum disorder 

2022-2024