Grant: Travel Awards - Institute Community Support

Depression and other stress-related mental health conditions are diagnosed in women almost twice as often as in men. Even so, most research has focused mainly on males, which means we still do not fully understand how biological sex influences the risk for these disorders. For example, an area that may play an important role in disorder risk is the gut microbiome-the community of bacteria living in the digestive system-which can affect the brain through what is known as the gut-brain axis. Research already shows that men and women have different gut bacteria, and early findings suggest that females may be more sensitive to stress-related changes in these microbes. This study aims to better understand how different aspects of biological sex contribute to stress vulnerability through the gut-brain-axis. Using a special mouse model that separates chromosomal sex (XX or XY) from gonadal sex (ovaries or testes), we collected gut bacteria from four different combinations of these sex traits. We then exposed bacteria-recipient mice to these gut contents and stressed them out to determine how the bacteria treatment modified stress-susceptibility. We measured anxiety- and depression-related behaviors, examined inflammation in the brain, and analyzed the mice's gut bacteria after the experiment. By studying how chromosomal sex, gonadal sex, and stress interact to shape the gut microbiome and influence behavior, this research helps clarify why stress-related disorders differ between males and females. These findings may eventually support more personalized approaches to mental-health treatment based on biological sex.