Impact of Antibiotics on Gut Microbiota Diversity and the Results of a Prospective Dietary Assessment in Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation

Abstract

<h3>Introduction</h3> Gut microbiota changes following autologous stem cell transplantation (ASCT) have been associated with reductions in progression-free survival but lack clear validation from independent transplant centers and laboratories (Khan et al, <i>Blood</i> 2018). The factors driving these changes are not well characterized. <h3>Objectives</h3> The primary objective of this study is to describe the changes to the gut microbiome in patients with multiple myeloma undergoing ASCT. Secondary objectives include describing the dietary characteristics of patients undergoing ASCT and other clinical covariates such as antibiotics that may influence the changes to the gut microbiome in this setting. <h3>Methods</h3> We performed a prospective analysis of changes to the gut microbiome following ASCT for patients with multiple myeloma using melphalan conditioning. Thirty patients were enrolled in the study and stool samples were collected at 4 timepoints: pre-transplant, post-transplant engraftment, day +100, and day +365. Samples underwent DNA extraction and 16S RNA sequencing for microbiota analysis using qiime and R software. Dietary analysis was performed using the online diet history questionnaire version 3.0 and collected prior to transplant. We are presenting the dietary results of the patient cohort prior to transplant and microbiota changes in the post-transplant samples for the first 7 subjects enrolled. <h3>Results</h3> Demographics are displayed in table one. Dietary analysis (table 2) reveals significant deficiencies in fiber, vegetable, and whole grain intake below national guideline recommendations. Microbiota changes revealed a significant loss of alpha diversity (<i>P =</i> 0.02) following transplant (figure 1A), which may be driven by antibiotic exposure, although this result was not statistically significant (<i>P</i> = 0.068, figure 1B). Two out of the 7 patients with available microbiota data demonstrated early disease progression before day 100, and analysis of the taxa changes at a genus level demonstrates a pronounced bloom of <i>bacteroides sp.</i> in these subjects (figure 2). <h3>Conclusions</h3> Multiple myeloma patients undergoing ASCT develop a significant loss of gut microbiome diversity, which may be related to broad-spectrum antibiotic exposure and is similar to observations at other transplant centers (El Jurdi, BBMT, 2019). To our knowledge, this is the first investigation to report prospective dietary information in a microbiome investigation in ASCT, which provides covariate information essential to understanding individualized changes to microbiota communities.