Early genistein exposure of California mice and effects on the gut microbiota-brain axis

Abstract

Human offspring encounter high amounts of phytoestrogens, such a s genistein (GEN), through maternal diet and soy-based formulas. Such chemicals can exert estrogenic activity and thereby disrupt neurobehavioral programming. Besides inducing direct host effects, GEN might cause gut dysbiosis and alter gut metabolites . To determine whether exposure to GEN affects these parameters, California mice ( Peromyscus californicus) dams were placed 2 weeks prior to breeding and throughout gesta tion and lactation on a diet supplemented with GEN (250 mg/kg feed weight) or AIN93G phytoestrogen-free control diet (AIN). At weaning, offspring socio-communicative be haviors, gut microbiota and metabolite profiles were assayed. Exposure of offspring to GE N-induced sexdependent changes in gut microbiota and metabolites. GEN expose d females were less likely to investigate a novel female mouse when tested in a thr ee-chamber social test. When isolated, GEN males and females exhibited increased latenc y to elicit their first call, suggestive of reduced motivation to communicate with other indi viduals. Correlation analyses revealed interactions between GEN-induced microbiome, metabolome and socio-communicative behaviors. Comparison of GEN males with AIN males revealed the fraction of calls above 20 kHz was associated with daidzein , -tocopherol, Flexispira spp. and Odoribacter spp. Results suggest early GEN exposure disrupts normal sociocommunicative behaviors in California mice, which are otherwise evident in these social rodents. Such effects may be due to GEN disruptions on ne ural programming but might also be attributed to GEN-induced microbiota shifts and resultant changes in gut metabolites. Findings indicate cause for concern that perinatal exposure to GEN may detrimentally affect the offspring microbiome-gut-brain axis.