Implications For Inflammation and Host-Microbiome Interactions In Bowel Dysfunction And Pain After Spinal Cord Injury

Abstract

Neurogenic bowel (NB) affects up to 60% of people with spinal cord injury (SCI) and is characterized by slow colonic transit, constipation, and chronic abdominal pain. NB rarely resolves and tends to worsen over time, making it a long-term physical and psychological challenge for people with SCI. The knowledge gap surrounding the underlying mechanisms of NB after SCI means that interventions are symptom-focused with only modest gains reported. Identifying the mechanism(s) that initiate and maintain NB after SCI is critically important to the development of evidence-based, novel therapeutic options for bowel dysfunction and pain after SCI. Using a translational spinal contusion mouse model that recapitulates the clinical NB symptoms after SCI, we can begin to tease apart the mechanisms underlying NB. Preliminary analyses using this model indicate a rapid and persistent increased expression of inflammatory mediators, expansion of lymphatic nodules, and disruption of the sterile intestinal mucus bilayer. Without the protective mucus barrier, microbes are observed translocating into the intestinal wall as early as 24 hours. These bacteria are known to initiate local host gene expression changes and may contribute to long term negative health outcomes. Follow-up analyses identified a corresponding upregulation in mRNA transcripts related to bacterial stimulation and defense responses in primary spinal afferents as well as hyperresponsiveness of primary vagal afferents to autologous stool samples. The potentially maladaptive colonic inflammation and host-microbiome interactions provide a biological substrate for NB after SCI with the potential for novel therapeutic interventions targeting these biological processes to prevent or treat NB.