Systemic IGF-1 administration prevents traumatic brain injury induced gut permeability, dysmorphia, dysbiosis, and the increased number of immature dentate granule cells.

Traumatic brain injury (TBI) occurs in 2-3 million Americans each year and is a leading cause of death and disability. Among the many physiological consequences of TBI, the hypothalamic pituitary axis (HPA) is particularly vulnerable, including a reduction in growth hormone (GH) and insulin-like growth factor (IGF-1). Clinical and preclinical supplementation of IGF-1 after TBI has exhibited beneficial effects. IGF-1 receptors are prominently observed in many tissues, including in the brain and in the gastrointestinal (GI) system. In addition to causing damage in the brain, TBI also induces GI system damage, including inflammation and alterations to intestinal permeability and the gut microbiome. The goal of this study was to assess the effects of systemic IGF-1 treatment in a rat model of TBI on GI outcomes. Because GI dysfunction has been linked to hippocampal dysfunction, we also examined proliferation and immature granule cells in the hippocampal dentate gyrus. 10-week-old male rats were treated with an intraperitoneal (i.p.) dose of IGF-1 at 4 and 24 h after lateral fluid percussion injury (FPI). At 3- and 35-days post-injury (DPI), gut permeability, gut dysmorphia, the fecal microbiome, and the hippocampus were assessed. FPI-induced permeability of the blood-gut-barrier, as measured by elevated gut metabolites in the blood, and this was prevented by the IGF-1 treatment. Gut dysmorphia and alterations to the microbiome were also observed after FPI and these effects were ameliorated by IGF-1, as was the increase in immature granule cells in the hippocampus. These findings suggest that IGF-1 can target gut dysfunction and damage after TBI, in addition to its role in influencing adult hippocampal neurogenesis.