PRJNA474710
The gut microbiome regulates behaviors related to depression, but not anxiety, through pro-inflammatory processes in the ventral hippocampus of stressed rats
Chronic exposure to stress is associated with increased incidence of depression, generalized anxiety and PTSD. However, stress induces vulnerability to such disorders only in a sub-population of individuals, as others remain resilient. While the physiological basis for stress vulnerability remains unclear, inflammation has emerged as a putative mechanism for promoting stress vulnerability. Inflammation can be mediated by gut microbiota, and several studies have show stress can perturb the gut microbiome. Our previous work showed that inflammation in the ventral hippocampus mediates stress vulnerability. The current study assessed the role of the microbiome in mediating stress vulnerability using a well-characterized model of stress vulnerability where male Sprague Dawley rats are subjected to 7 days of social defeat. Approximately half of the rats show short-latencies to social defeat (SL/vulnerable rats), and have increased anxiety-like and depression-like behaviors as well as increased inflammatory processes. The other half of socially-defeated rats in this model show long-latencies to defeat, and are similar to controls on measures of anxiety-like and depression-like behaviors, and show low levels of inflammatory markers. In this study, we used shotgun metagenome sequencing on fecal samples from SL/vulnerable rats and show increased expression of microbiota associated with an inflammatory phenotype, such as Clostridia, which we identify as a novel bacterial target associated with stress vulnerability. Fecal transplants from SL/vulnerable rats promoted a pro-inflammatory phenotype, including increased microglial density and IL-1ß expression in the ventral hippocampus. Fecal transplants from SL/vulnerable increased depression-like behaviors, but did not increase anxiety-like behaviors when given to non-stressed rats. Taken together, our results suggest the gut microbiome mediates depression-like, but not anxiety-like behaviors, in stress vulnerable rats, and the microbiome may mediate depression-like behaviors, at least in part, via inflammatory processes in the ventral hippocampus