Investigation of Oral Microbiome and Innate Inflammatory Response to Allogenic Stem Cell Transplant

Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) and usage of chemotherapy and antibiotics are thought to cause large changes in the gut and oral microbiome. Immunological disease that leads to the need for HSCT can also contribute to oral dysbiosis. Methods and Results Saliva samples were collected from a pilot group of HCST patients before and 1 month after transplant when blood neutrophil count had normalized. Just prior to the initiation of conditioning for transplant there are significant differences in species richness and evenness of distribution of oral bacteria taxa versus that in healthy controls. These are compounded after HSCT. Coincident with antibiotic treatment by the end of the interval much lower levels of bacteria taxa diversity were noted in many patients. The salivary microbiome showed presence of taxa normally identified with the juvenile state. One might speculate that depressed levels of Alloprevotella and Peptococcus and other microbiome abnormalities may contribute to the variable establishment of the newly grafted immune system and presence or lack of HSCT related sequelae. To start to better understand the local immune system post-HSCT a DNA epigenetic based identification of saliva granulocytes was done. It revealed differential levels of oral neutrophils, 58.5% +/_19.1 in patients post HSCT at the time of release from the hospital versus 70.8% +/- 6.18 in healthy age and gender matched controls – though blood levels were normal. Percentage oral monocytes trended higher in subjects after HSCT at time of release from the hospital P< 0.070, 17% +/- 25.7 in patients post-HSCT versus 5.5% +/- 3.4 in healthy controls. Conclusion In that microbial antigens and products play key roles in initial establishment of the immune system during development, one may postulate that antibiotic usage and the juvenile oral microbiome seen in post-HSCT mouth may contribute to aberrant inflammation, antigen presentation, and adaptive immune function post-HSCT, leading to both improper response to infection and GVHD.