Diversity and Richness Analysis of the Oral and Gastrointestinal Microbiome during Autologous Transplantation for Multiple Myeloma: Results of a Prospective Pilot Study and Correlation with Transplant Outcomes

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.4627-4627
• Main Authors: El Jurdi, Najla H, Filali, Ali, Salem, Iman, Retuerto, Mauricio, Dambrosio, Nina, Lazarus, Hillard M, Caimi, Paolo F, Creger, Richard, Cooper, Brenda, Tomlinson, Ben, Metheny, Leland, Malek, Ehsan, Otegbeye, Folashade, Sekaly, Rafick-Pierre, Ghannoum, Mahmoud, de Lima, Marcos
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-120038

Background The human microbiome has been associated with allogeneic hematopoietic cell transplantation (HCT) outcomes, namely infections, graft-versus-host disease and relapse. There are no studies describing the longitudinal changes in the oral or gastrointestinal microbiome in the setting of autologous HCT. We conducted a prospective study to describe the changes in microbial diversity in patients undergoing HCT for multiple myeloma (MM), and whether these correlate with HCT outcomes and/or toxicities. Methods Samples were collected from 15 MM patients on admission (baseline, T-2), during marrow aplasia (T+7) and after engraftment (T+30) (Table 1- summarizes baseline characteristics). We evaluated the bacterial and fungal microbiome of 15 patients using Ion-Torrent PGM workflow. The amplicons generated from the 16s rRNA and the ITS genes were sequenced for bacterial and fungal identification, respectively. Sequencing reads were clustered into operational taxonomic units (OTUs, 3% distance) and taxonomically classified via Qiime bioinformatics pipeline. Diversity was calculated using Shannon diversity index and richness using the R package ‘vegan‘. Longitudinal analysis was performed using all pairwise Multiple Comparison of Mean Ranks as implemented PMCMR plus R package, employing Kruskal & Wallis test followed by Bonferroni-Dunn post-hoc adjustment. Results Diversity and richness of the oral mycobiome decreased at T+7 compared to pre-transplant levels with further decrease noted at T+30, without reaching significance. Fecal mycobiome diversity and richness decreased from baseline to T+7 meeting statistical significance for diversity (T-2 vs T+7, p=0.05) and richness trended towards significance (p=0.06) with a further decrease noted at T+30. The temporal changes in bacterial diversity and richness in both oral and fecal samples did not reach statistical significance. (Figure1- Box and whisker plots of diversity and richness of the bacteriome and mycobiome at the genus levels from oral rinse and fecal samples) In fecal samples, bacterial diversity noted at T+7 during count nadir was associated with the severity of diarrhea experienced after myeloablation, with lower diversity correlating with more severe diarrhea (p= 0.03). Anaerobic targeting antibiotic exposure on or before T+7 affected both the genus diversity and richness at T+7 (p=0.015 and p=0.014, respectively). The bacterial genus richness at baseline (p=0.03) as well as the diversity and richnes