What Makes a Successful Donor? Fecal Transplant from Anxious-Like Rats Does Not Prevent Spinal Cord Injury-Induced Dysbiosis

SIMPLE SUMMARY: Spinal cord injury disrupts the composition of gut bacteria and increases the prevalence of anxiety-like and depressive-like behaviours. We have previously shown that a fecal transplant from uninjured donor rats prevents both injury-induced microbiota changes and the development of anxiety-like behaviour. In the present study, we aimed to determine whether donor selection would influence the efficacy of a fecal transplant after spinal cord injury. We found that a fecal transplant from uninjured donor rats with increased anxiety-like behaviour was not only ineffective in preventing injury-induced microbiota changes, but it also increased intestinal permeability and anxiety-like behaviour of the recipient rats. The results of this study emphasize the importance of optimal donor selection for successful fecal transplant treatment following spinal cord injury. ABSTRACT: Spinal cord injury (SCI) causes gut dysbiosis and an increased prevalence of depression and anxiety. Previous research showed a link between these two consequences of SCI by using a fecal transplant from healthy rats which prevented both SCI-induced microbiota changes and the subsequent development of anxiety-like behaviour. However, whether the physical and mental state of the donor are important factors in the efficacy of FMT therapy after SCI remains unknown. In the present study, rats received a fecal transplant following SCI from uninjured donors with increased baseline levels of anxiety-like behaviour and reduced proportion of Lactobacillus in their stool. This fecal transplant increased intestinal permeability, induced anxiety-like behaviour, and resulted in minor but long-term alterations in the inflammatory state of the recipients compared to vehicle controls. There was no significant effect of the fecal transplant on motor recovery in rehabilitative training, suggesting that anxiety-like behaviour did not affect the motivation to participate in rehabilitative therapy. The results of this study emphasize the importance of considering both the microbiota composition and the mental state of the donor for fecal transplants following spinal cord injury.