Modulation of the Oral Microbiome to Improve Oral Health and Reduce BSI from Oral Flora in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Randomized Controlled Trial

Abstract

Background Blood stream infections (BSI) in hematopoietic stem cell transplant (HSCT) patients with central venous catheters may arise from translocation of bacteria through a non-intact gastrointestinal mucosa and are known as mucosal barrier injury–laboratory confirmed blood stream infections (MBI-LCBI). Central venous catheter maintenance care doesn t prevent MBI-LCB and currently there are no proven strategies to prevent bacteremia secondary to mucosal barrier injury. Gingivitis and periodontitis are features of the mucosal toxicity seen post-HSCT and are associated with BSI frequency. Xylitol is a non-fermentable polysaccharide that reduces dental caries, plaque accumulation, and oral disease progression by inhibiting bacterial growth and community development. We hypothesized that daily dental xylitol, in addition to current oral care practice, is effective at reducing gingivitis, periodontitis and BSI from oral organisms. Methods We performed a prospective randomized controlled trial to test our hypothesis. All patients received standard oral care and half were randomized to additionally receive daily xylitol. Oral exams were performed at baseline and at intervals for the first 28 days post-HSCT. Metagenomic shotgun sequencing of gingival samples was performed at these same intervals. For patients who develop BSI, whole genome sequencing of bacterial isolates is being performed to assess for genetic relatedness to corresponding strains present within the patient s oral microbiome preceding the infection. Results We enrolled 35 patients, 17 cases and 18 controls before ending the study early for efficacy. Five patients withdrew from the study (3 cases, 2 controls). Patients who received xylitol had a significantly lower rate of gingivitis, oral plaque and oral ulcers greater than 10 mm. There was a significant decrease in BSI from oral organisms in the first 30 days post HSCT in the xylitol group, 0/14 (0%) vs 5/16 (31%) (p\u202f=\u202f0.04). Preliminary microbiome analysis showed decrease relative abundance of Candida albicans in patients receiving xylitol and individual patient analysis shows that xylitol may also impede Streptococcus mitis/oralis dominance in the oral microbiome. Additionally, we found that Staphylococcus aureus, a common cause of Central Line Associated Blood Stream Infection (CLABSI), was prominent in several gingival samples, suggesting BSI with Staphylococcus aureus may indeed be related to mucosal barrier injury. Conclusions The addition of xylitol to oral standard care appears to decrease BSI secondary to oral organisms, dental plaque, gingivitis and oral ulcerations in patients undergoing SCT.