Abstract

ABSTRACT Background Oral mucositis (OM) is a common side effect of conditioning therapy implemented before hematopoietic stem cell transplantation (HSCT). The role of oral microbiome in OM is not fully elucidated. Objective To determine oral microbiome profile changes post-conditioning in HSCT patients who developed moderate OM, or mild to no OM. Design Patient groups were: Muc0-1 with OM-score = 0–1 (43 paired samples) and Muc2 with WHO OM-score = 2 (36 paired samples). Bacterial DNA was isolated from oral samples (saliva, swabs of buccal mucosa, tongue, and supragingival plaque) at pre-conditioning (T 0 ), post-conditioning mucositis onset (T Muc ), and one-year post-conditioning (T Year ). 16S-rRNA gene next-generation sequencing was used to determine the relative abundance (RA) of >700 oral species. Alpha-diversity, beta-diversity and linear discriminant analyses (LDA) were performed Muc2 versus Muc0-1. Results Muc2 oral microbiome alpha- and beta-diversity differed between T 0 and T Muc . Muc2 alpha-diversity and Muc0-1 beta-diversity did not differ between T 0 and T Year . T 0 to T Muc LDA scores were significant in Muc2 for Gammaproteobacteria. For Muc2 patients, the average RA decreased for Haemophilus parainfluenza, a species known as mucosal surfaces protector, but increased for Escherichia-Shigella genera. Conclusions Post-conditioning OM might contribute to long-term oral microbiome changes affecting Gammaproteobacteria, in HSCT patients.

Highlights

  • Oral mucositis (OM) is a common side effect of conditioning therapy implemented before hematopoietic stem cell transplantation (HSCT)

  • Post-conditioning OM might contribute to long-term oral microbiome changes affecting Gammaproteobacteria, in HSCT patients

  • Oral mucositis (OM) is one of the most frequently occurring side effects associated with conditioning therapy

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Summary

Methods

Patient recruitmentPatients diagnosed with hematological cancers scheduled for conditioning therapy were recruited at Carolinas Medical Center–Atrium Health, Charlotte, North Carolina and enrolled in the prospective cohort study: ‘Multicenter Study on the Burden of Illness of Oral Side Effects from Conditioning Therapy Before Stem Cell Transplantation: Ora-stem Study [10]. The patient cohort was stratified for the time points “baseline” [T0] prior to conditioning, time of ‘oral mucositis occurrence’ [TMuc] , one-year post-transplant [TYear]), the number of paired samples obtained from four different oral sites, and the patient’s OM status: Muc group (moderate OM) and Muc0 group (no OM or mild OM) (Table 1). De-identified clinical characteristics of the patient cohort (n = 22) included: (i) worst WHO OM scores, (ii) hematological stem cell transplant type (autologous (4 Muc0 and 2 Muc patients)) or allogeneic (9 Muc0 and 7 Muc patients), (iii) hematological cancer diagnoses, paired oral samples (T0 to TMuc or T0 to TYear), and paired for all three time points, (iv) whether or not patients had received antibiotic prophylaxis treatment (levofloxacin) within 2 weeks prior to oral

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