Microbiome Influences on the neuroendocrine regulation of social behavior

Indiana University, Bloomington IN

Investigators

Abstract

Virtually all animals, including humans, play host to a wide range of microorganisms such as bacteria and fungi that function within cells, tissues, and organs. Many of these microorganisms reside within the gut. Recent evidence suggests that this 'gut microbiome' exerts a surprising and powerful influence on the normal brain and on behavior in both adults and the young. How the gut microbiome influences the brain and behavior, however, is essentially unknown. This research will test a novel mechanism by which the gut microbiome may contribute to the development of offspring sociality by focusing on the shared mother-offspring microbiome in dwarf hamsters. The goal of the proposed research is to test the idea that disruption of the maternal microbiome, via antibiotic administration, alters the diversity and composition of the mother's gut microbiome and consequently affects the development of normal social behavior and related physiological parameters in her offspring. This research will also test whether the restoration of the maternal gut microbiome returns social behaviors to normal. Lastly, these studies will examine the role of bi-parental (i.e., mother and father) behaviors in preventing the adverse effects of a disrupted maternal microbiome on offspring social behavior. Collectively, these studies will provide fundamental knowledge of the basic mechanisms by which the maternal microbiome influences the development of offspring sociality. An understanding of these mechanisms will provide important basic knowledge that may ultimately inform treatment and prevention of debilitating disorders characterized by deficits of social functioning. In addition to training graduate student researchers, undergraduates in Indiana University's Research Experience for Undergraduates program and a local middle school teacher and middle school class will take part in the research. The middle school students will participate in activities focused on soil and gut microbes at the local Marble Hill Farm. The precise physiological mechanisms underlying microbiome effects on the brain and social behavior, however, remain unknown. This research employs an animal model to elucidate the impact of maternal microbiome status on the development of offspring sociality as well as the mechanisms underlying observed microbiome-brain-behavior relationships. Specifically, the experiments utilize animals that display either bi-parental (i.e., both maternal and paternal) care or uni-parental (i.e., exclusively maternal) care to tease apart their relative contributions to offspring development. The goal of the proposed research is to test the specific hypotheses that: 1) disruption of the maternal microbiome via antibiotic administration alters the diversity and composition of gut microbiota and consequently offspring sociality, stress responsivity, and cytokine profiles; 2) disruption of neuroendocrine and/or neuroimmune systems mediates, at least in part, the effects on social behaviors; 3) repletion of the gut microbiome via fecal transplants restores normal social behaviors; and 4) bi-parental care modulates these effects by providing additional contributions of paternal behavior to buffer offspring. The proposed studies will provide valuable insight on the basic mechanisms of microbiome influences on maternal-offspring behavioral interactions, the role of paternal behaviors in buffering the influences of maternal microbiome disruption on offspring behavior, as well as the development of social behaviors more broadly.