A Literature Review on the Impact of the Gut Microbiome on Cancer Treatment Efficacy, Disease Evolution and Toxicity: The Implications for Hematological Malignancies

Abstract

The gut microbiome plays a crucial role in modulating the efficacy and toxicity of cancer therapies, particularly in hematological malignancies. This review examines the dynamic interplay between gut microbiota and cancer treatments, such as chemotherapy, immunotherapy, and hematopoietic stem cell transplantation (HSCT). Disruptions in the gut microbiome, known as dysbiosis, are associated with adverse effects like gastrointestinal toxicity, neutropenia and cardiotoxicity during chemotherapy. Conversely, the supplementation of probiotics has shown potential in mitigating these side effects by enhancing gut barrier function and regulating immune responses. In HSCT, a higher diversity of gut microbiota is linked to better patient outcomes, including reduced graft-versus-host disease (GVHD) and improved survival rates. The microbiome also influences the efficacy of immunotherapies, such as immune checkpoint inhibitors and CAR-T cell therapy, by modulating immune pathways. Research suggests that certain bacteria, including Bifidobacterium and Akkermansia muciniphila, enhance therapeutic responses by promoting immune activation. Given these findings, modulating the gut microbiome could represent a novel strategy for improving cancer treatment outcomes. The growing understanding of the microbiome's impact on cancer therapy underscores its potential as a target for personalized medicine and offers new opportunities to optimize treatment efficacy while minimizing toxic side effects.

Keywords: cancer therapy; dysbiosis; gut microbiome; hematological malignancies; immunotherapy; probiotics.

Figure 1

Microbiota interactions with pharmacokinetics and pharmacodynamics. 1—Faecalibacterium prausbitzii increases the necessary dose of Tacrolimus due to inactivation; 2a—cyclophosphamide (CTX) induces Enterococcus hirae and Lactobacillus species translocation to lymphoid structures and enhances immune response; 2b—antibiotics block bacterial translocation, leading to a reduced response to CTX; 3—methotrexate (MTX) and disrupted microbiome flora have a reciprocal influence; 4—3-methyl-xantine-producing flora leads to enhanced cisplatin toxicity through dopamine receptor D1 (observed only in epithelial tumors, not in lymphoma).

Figure 2

Microbiome shifts and treatment-related toxicity in hematological malignancies. Blue indicates a favorable effect, while red indicates an unfavorable effect. Upward arrows (↑) represent an increased abundance of the bacterial genus, whereas downward arrows (↓) indicate a reduced abundance.