Impact of diet and antibiotics on gut microbiota and outcomes in patients with multiple myeloma treated with autologous hematopoietic stem cell transplantation

Recent years have brought fascinating developments that the commensal microbes we carry with us can impact health outcomes. There is growing awareness that commensal microbes in the gut, also known as the gut microbiome or microbiota, are essential to normal immune function and can impact efficacy and toxicity of cancer treatment for patients with solid tumors and hematologic malignancies in clinical practice [1–5]. The gut microbiota can be heavily impacted by diet and antibiotic exposure, with potential downstream effects on immune function. Microbial digestion of plant-derived dietary fiber produces bioactive metabolites such as short chain fatty acids (e.g. butyrate) which may serve as mediators of host-microbe interactions that impact immune function [6], supporting rationale for capturing dietary information in microbiome studies. In patients with melanoma receiving immune checkpoint inhibitor therapy, dietary fiber intake has been associated with superior responses to therapy [7], highlighting the potential impact of diet on microbiota with downstream impacts on immune function and antitumor immunity. In multiple myeloma(MM) patients, higher relative abundance of butyrate-producing microbes in the stool has been associated with minimal residual disease (MRD) negativity after initial therapy for MM [8]. An important problem with existing data are that dietary information is lacking from most prospective microbiome studies in patients. In this issue of Leukemia and Lymphoma, D’Angelo et al. [9] report their findings from a prospective study of the gut microbiota and their diets in 30 patients with multiple myeloma undergoing autologous stem cell transplantation. These data add to a growing body of work connecting changes in the microbiota to clinical outcomes in treatment of hematologic malignancies with autologous stem cell transplantation [6,10]. Importantly, in addition to longitudinal stool sampling performed in order to profile the gut microbiota, D’Angelo et al. sought to capture dietary patterns using surveys of the participants to evaluate a hypothesis that higher fiber intake and diet quality impacts microbiota community structure and may be associated with outcomes after transplant. The authors found that although the patients in the highest quartile in dietary fiber intake had the highest alpha diversity pre-transplant, their gut microbiota’s alpha diversity measures were not significantly higher than those in the lowest quartile of dietary fiber intake. Alpha diversity is a numerical measure used in microbiome studies to summarize the distribution of species abundance in a given sample which depends upon species richness(number) and evenness (distribution); higher diversity can commonly reflect a healthy microbiota. Intriguingly, the authors found that a lower degree of diversity at time of engraftment was associated with inferior response (partial response, PR vs. very good partial response/complete response, VGPR/CR). Microbiota injury as measured by lower diversity at engraftment was driven by a high degree of use of broad-spectrum antibiotics in this group of patients (24/30, 80%) which likely greatly influenced the microbiota community structure early after transplantation and may impede ability to detect associations between diet and outcomes in this study. In contrast with other published studies describing microbiota after autologous hematopoeitic stem cell transplant in multiple myeloma [10,11], the authors also analyzed stool samples at 100 days and 9–12months after transplant, demonstrating early and sustained recovery of diversity of the gut microbiota post-transplant.