The microbiome and the immune system are known to work in conjunction to modulate the clearance of pathogens and tolerance of beneficial microbes. A growing area of research seeks to study the potential extent of the involvement of the microbiome in modulating and supporting the immune system during acute allograft rejection. It has been hypothesized that the localized microbiota in each organ produce metabolites that instigate inflammatory immune responses, but whether microbiota interactions precipitate acute allograft rejection is unknown. Therefore, this study focuses on microbiome shifts in the gut and kidney after inducing acute renal transplant rejection in order to implicate gut dysbiosis as a precursor or supporter of allograft rejection. This study also subsequently explores the use of an immune-modulating protein in order to determine differences in the outcome of transplant rejection and potential differences in intestinal microbial load. This experiment sought to induce rejection in BALB/c mice through the use of C57BL/6 mouse renal slivers. Microbiome abundance was analyzed in all experimental groups. Understanding the role of the microbiome in transplant rejection has vast clinical implications and has the potential to enhance pre- and post-operative treatment, and immune management and quality of life following organ transplant.