Effects of Soy-Based Infant Formula on Obesity and Neurodevelopment in an Autism Mouse Model

OBJECTIVES: Mice fed soy-based diets exhibit increased weight gain compared to mice fed casein-based diets and the effects are more pronounced in a model of fragile X syndrome (FXS; Fmr1(KO)). FXS is a neurodevelopmental disability characterized by intellectual impairment, seizures, autistic behavior, anxiety, and obesity. We hypothesize that high consumption of soy protein during postnatal development is a dietary exposure that increases the risk of developing obesity, particularly in vulnerable populations such as FXS. Here, we analyzed body weight as a function of mouse age, diet, and genotype to determine the effect of diet on weight gain. We also assessed plasma protein biomarker expression and behavior in mice in response to diet. Medical record and survey data were employed to identify associations between infant formula, weight gain and neurological development in children. METHODS: Methods include prospective and retrospective evaluation of weight gain and neurological outcomes in mice and humans, respectively, as a function of postnatal diet. RESULTS: Juvenile Fmr1(KO) mice fed a soy protein-based rodent chow throughout gestation and postnatal development exhibit increased weight gain compared to mice fed casein-based purified ingredient diet or grain-based, low phytoestrogen chow. Adolescent and adult Fmr1(KO) mice fed a soy-based infant formula diet exhibited increased weight gain compared to reference diets. Increased body mass was due to increased lean mass. Wild type male mice fed soy-based infant formula exhibited increased learning in a passive avoidance paradigm and Fmr1(KO) male mice had a deficit in nest building. Mice consuming a soy-based infant formula diet exhibited altered expression of numerous plasma proteins including the adipose hormone leptin and the β-amyloid degrading enzyme neprilysin. Consumption of soy-based infant formula was not associated with obesity at 6 years of age in children but was associated with an increased need for support in school. CONCLUSIONS: In conclusion, single-source, soy-based diets may contribute to the development of obesity and the exacerbation of neurological phenotypes in developmental disabilities through a β-amyloid-mediated pathway. FUNDING SOURCES: This work was supported by the National Institutes of Health, FRAXA Research Foundation, RayBiotech and the United States Department of Agriculture.