The gut-brain-microbiota axis is increasingly being recognized as an important mediator of overall health and well-being. Significant changes in mental health status including anxiety, depression and cognitive dysfunctions can occur concurrently with systemic diseases. These include, but are not limited to, irritable bowel syndrome, inflammatory bowel disease, hepatic encephalopathy, and diabetes. Critically, changes in the microbiota have been described to occur during these maladies. Highlighting the importance of the microbiota, changes in diversity due to challenge with a bacterial pathogen can cause stress-induced behavioral changes in adult mice. While the effects of the microbiota-gut-brain axis on mental health are emerging in adult mouse models, the critical factors responsible for the establishment of the axis during development are currently unknown. Early life is a time of rapid learning and development. Neonates are more susceptible to serious complications arising from challenge with a bacterial pathogen, than adults. Consequently, neonates must be studied appropriately. Exposure to stress in early life in the form of maternal separation is associated with alterations in the microbiota-gut-brain axis in adulthood, well past exposure to the stressor. These alterations include depressive disorders (as measured by anhedonia), anxiety, cognitive deficits, acute stress-mediated intestinal dysfunction, increased susceptibility to chemical-induced colitis, infection with pathogens, and increased ethanol preference, to name a few. Therefore, changes that affect the establishment of the gut-brain-microbiota axis in the neonatal periods may have profound effects, including mental health issues, throughout life. The overall goals of this project are to determine the effect of neonatal manipulation of the microbiota using challenge with a bacterial pathogen on the development of the microbiota-gut-brain axis. This will be achieved via challenge with enteropathogenic E. coli (EPEC) in neonates, with behavioral and cognitive changes assessed in adulthood, assessing potential host microbial factors, and host defense factors including mucosal barrier function and pattern recognition receptors. Completion of these studies will yield important information regarding the development of the microbiota-gut-brain axis and greater understanding of the regulation of key factors in mental health and well-being.
The overall goal of this project is to understand how mental health is impacted by dysbiosis of the intestinal microbiota, during the neonatal period of life. Alterations in the microbiota-gut-brain axis are known be present in individuals suffering from anxiety, depression, memory loss, irritable bowel syndrome, and inflammatory bowel disease. Induction of dysbiosis, following bacterial infection in neonates, to decipher the mechanisms mediating these pathways will lead to better understanding of the role of the microbiota in early life in programming of the gut-brain axis in adulthood and possibly novel therapeutic targets in treating mental health and well-being.
| Pusceddu, M M; Murray, K; Gareau, M G (2018) Targeting the Microbiota, from Irritable Bowel Syndrome to Mood Disorders: Focus on Probiotics and Prebiotics. Curr Pathobiol Rep 6:1-13 |
| Pusceddu, Matteo M; Gareau, Melanie G (2018) Visceral pain: gut microbiota, a new hope? J Biomed Sci 25:73 |
| Gareau, M G (2016) Cognitive Function and the Microbiome. Int Rev Neurobiol 131:227-246 |
