Gut microbiome in multiple myeloma: Mechanisms of progression and clinical applications

Abstract

The gut commensal microbes modulate human immunity and metabolism through the production of a large number of metabolites, which act as signaling molecules and substrates of metabolic reactions in a diverse range of biological processes. There is a growing appreciation for the importance of immunometabolic mechanisms of the host-gut microbiota interactions in various malignant tumors. Emerging studies have suggested intestinal microbiota contributes to the progression of multiple myeloma. In this review, we summarized the current understanding of the gut microbiome in MM progression and treatment, and the influence of alterations in gut microbiota on treatment response and treatment-related toxicity and complications in MM patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, we discussed the impact of gut microbiota-immune system interactions in tumor immunotherapy, focusing on tumor vaccine immunotherapy, which may be an effective approach to improve anti-myeloma efficacy.

The Interaction between Gut Microbiota and Host Amino Acids Metabolism in Multiple Myeloma

“…Treated with concurrent therapies that significantly alter the composition of the gut microbiota, including immunosuppressants, broad-spectrum antibiotics, etc, these patients commonly had intestinal dysbiosis [ 68 , 69 ]. Indeed, analyses of longitudinal fecal samples demonstrated a loss of bacterial diversity after HSCT [ 70 , 71 , 72 , 73 , 74 ], demonstrating that the diversity of the gut microbiota of MM patients with auto-HSCT lowered before transplantation, and then lowered further during transplantation [ 71 ]. Moreover, MM patients with a low diversity of gut microbiota during transplantation had an impaired transplantation response [ 72 ], while those with a high diversity of gut microbiota had better transplantation results and lower transplant-related mortality [ 71 ].…”

“…During the pretreatment stage of melphalan, a higher abundance of Bacteroides was discovered to be associated with the reduced incidence of severe diarrhea, while a higher abundance of Blautia and Ruminococcus was closely related to severe diarrhea and post-transplant nausea and vomiting [ 73 ]. Meanwhile, the significant susceptibility to bloodstream infections (BSI) remained another toxicity of HSCT with lowered diversity and intestinal dysbiosis [ 74 ]. Studies have reported that with low diversity of gut microbiota and dominance of specific bacteria (mainly enterococcus , streptococcus , and various proteobacteria ), bacteremia remarkedly increased during HSCT [ 75 ].…”

“…Nonetheless, the inherent mechanisms of SCFAs on MM progression remain poorly understood, SCFAs were reported to skew the balance of inflammatory cytokines locally and systemically or modulate immunity regarding cancer development and progression or response to therapy [ 90 , 91 ]. In fact, the functions of the anti-tumor role have been extended to recognize mechanisms that alleviate MM progression, including SCFAs that either inhibit inflammatory factors (such as IL-1β, IL-6, and TNF-a) or induce the expression of anti-inflammatory factors (such as IL-10), all of which were considered to be at a high level in the bone marrow microenvironment [ 74 ].…”

Exploring the causal relationship between gut microbiota and multiple myeloma risk based on Mendelian randomization and biological annotation

“…Despite the challenges of obtaining real-time microbiome data in clinical practice, retrospective studies have started illuminating the relationship between changes in particular microbial characteristic and MM ( Zhang et al, 2022 ). Due to confounding factors such as lifestyle, environment, host gene mutations, and potential reverse causality, the precise association between genes in MM patients and gut microbiota remains underexplored.…”

The causal relationship of gut microbiota in progression of seven common hematological malignancies

“…The dysbiosis of GM has the potential to induce alterations in GM-derived metabolites, which act as signaling molecules and substrates for immune and metabolic responses. This, in turn, may play a role in the advancement of hematologic malignancies [12]. Recent studies have revealed a considerable reduction in GM diversity in all types of leukemia investigated, that persists even after ve years of survival [13][14][15][16][17][18][19].…”