Diet-microbiome interactions in cancer treatment: Opportunities and challenges for precision nutrition in cancer

Abstract

Dietary patterns contribute to cancer risk. Separately, microbial factors influence the development of several cancers. However, the interaction of diet and the microbiome and their joint contribution to cancer treatment response needs more research. The microbiome significantly impacts drug metabolism, immune activation, and response to immunotherapy. One of the critical factors affecting the microbiome structure and function is diet. Data demonstrate that the diet and microbiome composition affects the immune response. Moreover, malnutrition is a significant confounder to cancer therapy response. There is little understanding of the interaction of malnutrition with the microbiome in the context of cancer. This review aims to address the current knowledge of dietary intake patterns and malnutrition among cancer patients and the impact on treatment outcomes. Second, this review will provide evidence linking the microbiome to cancer treatment response and provide evidence of the potentially strong effect that diet could have on this interaction. This review will formulate critical questions that will need further research to understand the diet-microbiome relationship in cancer treatment response and directions for future research to guide us to precision nutrition therapy to improve cancer outcomes.

Keywords: Cachexia; Dietary intake; Dietary risk factors; Malnutrition; Oncology; Quality of life.

Fig. 1

Concept map of the diet-microbiome relationship in cancer treatment. (1) Prior to diagnosis, dietary patterns can affect both microbiome structure/function and malnutrition status at diagnosis, as well as treatment outcomes . (2) At diagnosis, microbiome structure/function affects anti-cancer therapy effectiveness, and possibly effects dietary intake and malnutrition status. Subsequently, dietary intake and malnutrition status can affect nutrient and drug metabolism, which itself can mediate* the relationship between dietary intake, malnutrition and treatment response. (3) During treatment, anti-cancer therapy affects dietary intake, malnutrition, and microbiome structure/function. The microbiome also impacts treatment response, which is likely mediated* by nutrient and drug metabolism. Other diseases states show a relationship between microbiome structure/function and malnutrition status, but this had not been demonstrated specifically for cancer. Note: While this model does not include the contribution of the immune system, it is understood to play a key role. (solid arrows = direct evidence; transparent arrows = indirect evidence).

Fig. 2

Microbial interactions in the process of carcinogenesis and effects of diet and drug therapy on cancer treatment outcomes. Top panel: A) Microbial homeostasis is conferred by an immunocompetent immune system, microbial diversity, double mucus layer, epithelial tight junctions, and production of antimicrobial peptides, B) Disturbances in microbial homeostasis occur through gene mutations, loss of diversity, pathogen invasion, increased expression of virulence factors, development of biofilms, release of bacterial metabolites/toxins, and activation of inflammatory pathways, C) Neoplastic transformation of epithelial cells resulting from gene mutations and metabolic changes that alter bacterial attachment, reduce tight junctions, and allow microbes and microbial products intimate contact with the tumor cells, D) Additional tumor mutations and extravasation of tumor cells provide microbes with opportunities to invade the tumor microenvironment, tumor cells, and interact with immune cells to confer immune evasion. Bottom panel: Anti-cancer therapies induce changes in the microbiome, gut barrier function, epithelial structure leading to deleterious side effects. Dietary patterns are implicated in mediating some of these treatment effects. Note: While this example is focused on CRC, several mechanism and factors represented are also relevant to other solid tumors. Created with BioRender.com.