Role of the Microbiome and Diet for Response to Cancer Checkpoint Immunotherapy: A Narrative Review of Clinical Trials

Curr Oncol Rep. 2025 Jan 3. doi: 10.1007/s11912-024-01622-6. Online ahead of print.

Abstract

Purpose of review: The advent of checkpoint immunotherapy has dramatically changed the outcomes for patients with cancer. However, a considerable number of patients have little or no response to therapy. We review recent findings on the connection between the gut microbiota and the immune system, exploring whether this link could enhance the effectiveness of immunotherapy.

Recent findings: Clinical studies have reported specific types of bacteria in larger quantities at baseline in responders than in non-responders, especially Akkermansia mucinifila, Ruminococcaceae, Faecalibacterium, and Lachnospiraceae. Following the consumption of a high-fiber diet, bacteria in the gut ferment dietary fiber to short-chain fatty acids (SCFAs), like acetate, propionate, and butyrate. Some of the SCFAs nurture intestinal epithelial cells, and some enter the bloodstream. Here SCFAs can activate DC8 + cytotoxic T-cells to induce cancer cell death. High fiber intake in the diet was associated with a reduced risk of progression or death during checkpoint immunotherapy. Recent findings demonstrate that high-fiber plant-based diets such as the Mediterranean Diet positively influence the gut microbiota whereas antibiotics and proton pump inhibitors can negatively influence outcomes of cancer immunotherapy by changing the gut microbiota. This narrative review provides evidence of an association between types of bacteria and their metabolites and favorable responses to checkpoint immunotherapy. Prospective clinical trials are needed to determine if diet interventions can improve treatment outcomes.

Keywords: Cancer Immunotherapy; Dietary fiber; Gut Microbiota; Mediterranean Diet; Short-chain Fatty Acids.

Publication types

  • Review