Gut microbiota is a critical regulator of hosts metabolism, immune system and cognitive function. However, the microbiome-gut-brain axis has not been systematically studied in Inflammatory Bowel Disease (IBD), much less in posttraumatic stress disorder (PTSD). A novel experimental "2-hit" model (IBD-PTSD) is established, where mice are subjected to dextran sulfate sodium (DSS)-induced ulcerative colitis and then conditioned fear (CF) memory test, to study the role of microbiome-gut-brain axis in these inflammatory pathologies. We found that DSS-induced colitis led to contextual memory deficit in both male and female mice, even when colitis-associated disease symptoms such as diarrhea and rectal bleeding have subsided. Molecular characterization showed prolonged neuroinflammation and astrogliosis in the mice that had been exposed to DSS. These data have been published in the peer-reviewed journal Molecular Brain. New data showed that ghrelin attenuated DSS-induced colitis, exerting anti-inflammatory effects in the recovery phase, and promoting tissue repair in part through regulating epithelial metabolism via PPARgamma mediated signaling; however, ghrelin treatment is insufficient to rescue neuroinflammation induced by peripheral inflammation.