Microbiome in Cancer Development and Treatment

Abstract

Targeting the microbiome, microbiota-derived metabolites, and related pathways represents a significant challenge in oncology. Microbiome analyses have confirmed the negative impact of cancer treatment on gut homeostasis, resulting in acute dysbiosis and severe complications, including massive inflammatory immune response, mucosal barrier disruption, and bacterial translocation across the gut epithelium. Moreover, recent studies revealed the relationship between an imbalance in the gut microbiome and treatment-related toxicity. In this review, we provide current insights into the role of the microbiome in tumor development and the impact of gut and tumor microbiomes on chemo- and immunotherapy efficacy, as well as treatment-induced late effects, including cognitive impairment and cardiotoxicity. As discussed, microbiota modulation via probiotic supplementation and fecal microbiota transplantation represents a new trend in cancer patient care, aiming to increase bacterial diversity, alleviate acute and long-term treatment-induced toxicity, and improve the response to various treatment modalities. However, a more detailed understanding of the complex relationship between the microbiome and host can significantly contribute to integrating a microbiome-based approach into clinical practice. Determination of causal correlations might lead to the identification of clinically relevant diagnostic and prognostic microbial biomarkers. Notably, restoration of intestinal homeostasis could contribute to optimizing treatment efficacy and improving cancer patient outcomes.

Keywords: cancer treatment efficacy; cardiotoxicity; cognitive impairment; dysbiosis; fecal microbiota transplantation; late effects; probiotics; the gut microbiome.

Figure 1

Microbial homeostasis (A) and intestinal dysbiosis induced by cancer and corresponding treatment (B). The intact commensal microbiota helps to maintain the balance between pro- and anti-inflammatory responses of the immune system (A). Chemo- and radiotherapy-associated dysbiosis and mucosal barrier disruption might lead to bacterial translocation, pro-inflammatory cytokine release, and mucosal inflammation (B). Abbreviations: DAMPs, damage-associated molecular patterns; IgA, immunoglobulin A; PAMPs, pathogen-associated molecular patterns; SFB, segmented filamentous bacteria; TGF-β, transforming growth factor-beta; TNF-α, tumor necrosis factor-alpha; Treg, regulatory T cells.

Figure 2

The impact of microbiota modulation using probiotics or FMT in cancer patients. Restoration of favorable microbiome composition and increased integrity of the intestinal barrier might lead to improved cancer patient outcomes via increased efficacy and reduced toxicity of cancer treatment. Abbreviations: FMT, fecal microbiota transplantation.