Talk abstracts
Talk on Thursday 04:30-04:45pm submitted by Ashley Cyr
Beyond the Lesion: How Spinal Cord Injury Modulates the Gut Microenvironment
Ashley Cyr (Department of Neuroscience, Neuroscience Graduate Program, Belford Center for Spinal Cord, Center for Brain and Spinal Cord Repair), Katherine Mifflin (Department of Neuroscience, Belford Center for Spinal Cord Injury, Center for Brain and Spinal Cord Repair), Kristina Kigerl (Department of Neuroscience, Belford Center for Spinal Cord Injury, Center for Brain and Spinal Cord Repair), Phillip Popovich
Abstract:
Traumatic spinal cord injury (SCI) is a life-altering condition affecting an estimated 300,000 people in the United States. Though SCI is known for its motor and sensory deficits, it also disrupts autonomic pathways that influence other organ systems, including the gastrointestinal tract (i.e., the gut). These disruptions alter the gut microbiome, a process termed dysbiosis, and promote intestinal inflammation, both of which have been linked to impaired neurological recovery. Yet how injury-induced changes in microbiota and inflammation interact to shape the gut microenvironment remains unknown. In the present study, we used germ-free and colonized mice, with or without a thoracic SCI (T9 complete crush), to systematically study the relative contributions of disrupted CNS signaling and enteric microbiota on the gut microenvironment. Histopathological techniques were used to assess intestinal morphology, while immunohistochemistry was used to quantify macrophages and lymphocytes. Colonization significantly reduced villus surface area, supporting the hypothesis that germfree mice maintain longer villi as a compensatory mechanism to counteract the absence of microbiotamediated digestion. The villus height-to-crypt depth ratio (VH:CD), a key indicator of intestinal health, was significantly reduced only in SCI colonized mice, suggesting that the interaction between microbiota and injury drives structural damage. Additionally, we observed a colonizationdependent increase in gut macrophages, consistent with the lower immune surveillance demands of germfree intestinal tissue in the absence of microbial colonization. Furthermore, T cells were upregulated in SCI-colonized mice, suggesting that injury-induced gut dysbiosis activates an adaptive immune response. Collectively, these results advance our understanding of how SCI-induced alterations in the gut microbiome and immune landscape influence the gut microenvironment. Future research will investigate how these histological changes impact gastrointestinal function by examining whether structural damage contributes to malabsorption and nutrient deficits, and by validating the immunological quantification using flow cytometry.
Keywords: Spinal Cord Injury , Gut Dysbiosis , Microbiome