Biomarker expression level changes within rectal gut-associated lymphoid tissues in spinal cord-injured rats.

Abstract

Neurogenic bowel dysfunction (NBD) is common after spinal cord injury (SCI). Gut-associated lymphoid tissue (GALT), an organized structure within the mucosal immune system, is important for the maintenance of gut homeostasis and body health and serves as the first line barrier/defense against diet antigens, commensal microbiota, pathogens, and toxins in mucosal areas. The current study examined gene expression levels along six segments of anorectal tissue using real-time polymerase chain reaction (RT-PCR) in uninjured rats (28-day sham surgical controls) and at both 28- and 42-days post-T9 contusion injury. Consistent with our previous report of functional regional differences in the ano-rectum, we demonstrate the existence of GALTs located primarily within the segment at 3-4.5 cm from the rectal dentate line (termed rectal GALTs-rGALTs) in shams with upregulated gene expression levels of multiple biomarkers, including B cell and T cell-related genes, major histocompatibility complex (MHC) class II molecules, and germinal center (GC)-related genes, which was further confirmed by histologic examination. In the same rectal tissue segment following T9 SCI, inflammation-related genes were upregulated at 28 days post-injury (DPI) indicating that microbial infection and inflammation of rGALTs modified structure and function of rGALTs, while at 42 DPI rGALTs exhibited resolution of inflammation and impaired structure/function for extrafollicular B cell responses. Taken together, our data suggest that rGALTs exists in rat rectum for homeostasis of gut microbiota/barrier. SCI induces microbial infection and inflammation in rectal tissues containing rGALTs, which could contribute to development of SCI-related gut microbiome dysbiosis, NBD, and systemic diseases.