Gastrointestinal Microbiome and Mycobiome Changes during Autologous Transplantation for Multiple Myeloma: Results of a Prospective Pilot Study

Abstract

Microbiome dysbiosis has been associated with adverse outcomes of hematopoietic cell transplantation (HCT). We hypothesized that exposure to high-dose melphalan and antimicrobials in patients undergoing autologous HCT for plasma cell disorders results in oral and gastrointestinal microbial dysbiosis, which in turn is associated with regimen-related toxicities. We conducted a prospective study describing the longitudinal changes in oral and gastrointestinal bacteriome and mycobiome in this patient population. Our findings show that microbiome composition present at baseline is associated with the incidence and severity of post-transplantation nausea, vomiting, and culture-negative neutropenic fever, as well as with the rate of neutrophil engraftment. We also have evidence of an association between the microbial communities at count nadir and the development of regimen-related gastrointestinal toxicities commonly observed after exposure to high-dose melphalan. Although bacteriome diversity largely recovers within 1 month after transplantation, we observed a continuous decrease in oral and gastrointestinal mycobiome diversity, suggesting that the mycobiome requires a longer time to recover compared with the bacteriome.

Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study

“…These observations are consistent with previous single-center analyses of 8, 15, and 28 patients each. 25,43,44 Importantly, we observed that patients with greater degree of microbiome damage, as assessed by below-median fecal diversity around the time of neutrophil engraftment, had higher rates of progression following transplantation.…”

Observational Cohort Study of Oral Mycobiome and Interkingdom Interactions over the Course of Induction Therapy for Leukemia

“…Similarly, patients with a baseline microbiome community dominated by Candida and aciduric bacteria were more likely to develop oral candidiasis during antineoplastic treatment (9). Recently, variation in mycobiome composition was linked to treatment-related toxicities after autologous HSCT for multiple myeloma (10). Specifically, the composition of the baseline oral mycobiome was associated with vomiting as well as culture-negative neutropenic fever, while the fungal community on day 7 posttransplantion was associated with the incidence and severity of mucositis.…”

“…In addition to chemotherapy, antimicrobial therapy, a very common practice in this patient population, impacts mycobiome composition. For example, it was observed that antibiotics with antianaerobic activity affected the oral fungal community composition posttransplantion in multiple myeloma patients (10). Also, bacteremia with fluconazole-resistant Candida has been associated with exposure to several different antimicrobials, including carbapenems, clindamycin, and colistin (15).…”

Summary of the Third Annual Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling

“…In addition, it will be important that the myeloma research community continue to conduct smaller studies using other methodologies such as molecular-based tools to explore the immune microenvironment and identify novel immune signatures that may be associated with response or outcomes. Recent data from studies exploring the gastrointestinal microbiome suggest that we need to expand our scope beyond peripheral blood and bone marrow studies when evaluating the IP [64,65].…”