RESUMO
Inflammatory bowel diseases (IBDs) are chronic intestinal diseases, frequently associated with comorbid psychological and cognitive deficits. These neuropsychiatric effects include anxiety, depression, and memory impairments that can be seen both during active disease and following remission and are more frequently seen in pediatric patients. The mechanism(s) through which these extraintestinal deficits develop remain unknown, and the study of these phenomenon is hampered by a lack of murine pediatric IBD models. Herein we describe microbiota-gut-brain (MGB) axis deficits following induction of colitis in a pediatric setting. Acute colitis was induced by administration of 2% dextran sodium sulfate (DSS) for 5 days starting at weaning [postnatal day (P)21] causing reduced weight gain, colonic shortening, and colonic inflammation by 8 days post-DSS (P29), which were mostly resolved in adult (P56) mice. Despite resolution of acute disease, cognitive deficits (novel object recognition task) and anxiety-like behavior (light/dark box) were identified in the absence of changes in exploratory behavior (open field test) in P56 mice previously treated with DSS at weaning. Behavioral deficits were found in conjunction with neuroinflammation, decreased neurogenesis, and altered expression of pattern recognition receptor genes in the hippocampus. Additionally, persistent alterations in the gut microbiota composition were observed at P56, including reduced butyrate-producing species. Taken together, these results describe for the first time the presence of MGB axis deficits following induction of colitis at weaning, which persist in adulthood.NEW & NOTEWORTHY Here we describe long-lasting impacts on the microbiota-gut-brain (MGB) axis following administration of low-dose dextran sodium sulfate (DSS) to weaning mice (P21), including gut dysbiosis, colonic inflammation, and brain/behavioral deficits in adulthood (P56). Early-life DSS leads to acute colonic inflammation, similar to adult mice; however, it results in long-lasting deficits in the MGB axis in adulthood (P56), in contrast to the transient deficits seen in adult DSS. This model highlights the unique features of pediatric inflammatory bowel disease.