Caloric restriction worsens decision-making impairments and gut dysbiosis after brain injury in male rats

Abstract

Traumatic brain injury (TBI) causes long-term deficits in decision-making and disrupts the gut microbiome. Dysbiosis of the gut microbiome is a potential contributor to the development of multiple psychiatric and neurological disorders and may be a contributor to chronic symptoms from TBI. Caloric restriction is often used to assess psychiatric-related behaviors in animals, but also affects the gut microbiome. Thus, understanding how caloric restriction interacts with the microbiome, injury processes, and behavioral outcomes is critical. In the current study, we evaluated the effects of caloric restriction versus free feeding on a frontal controlled cortical impact TBI. Rats were trained on the rodent gambling task, an analog of the Iowa gambling task, to assess risk-based decision-making. The microbiome was sampled through the acute to subacute period post-injury and lesion size and microglia counts evaluated at 10 weeks post-injury. Caloric restriction did not affect decision-making at baseline, but did affect motivational variables. TBI impaired decision-making and this effect was exacerbated by caloric restriction. Other motivation-related variables followed a similar pattern of impairment with TBI driving impairments that were worsened by caloric restriction. The gut microbiome was initially dysbiotic, but largely recovered within 14 days post-injury. Despite this, acute gut measurements were predictive of chronic decision-making impairment. This finding could indicate a role for the gut microbiome in modifying acute and subacute TBI pathology and suggest that interventions targeting the gut may have a limited window of opportunity to treat long-term deficits.