Can the microbiota predict response to systemic cancer therapy, surgical outcomes, and survival? The answer is in the gut

ABSTRACT

Introduction

The gut microbiota seems to play a key role in tumorigenesis, across various hallmarks of cancer. Recent evidence suggests its potential use as a biomarker predicting drug response and adding prognostic information, generally in the context of immuno-oncology.

Areas covered

In this review, we focus on the modulating effects of gut microbiota dysbiosis on various anticancer molecules used in practice, including cytotoxic and immune-modulating agents, primarily immune-checkpoint inhibitors (ICI). Pubmed/Medline-based literature search was conducted to find potential original studies that discuss gut microbiota as a prognostic and predictive biomarker for cancer therapy. We also looked at the US ClinicalTrials.gov website to find additional studies particularly ongoing human clinical trials.

Expert commentary

Sequencing of stool-derived materials and tissue samples from cancer patients and animal models has shown a significant enrichment of various bacteria such as Fusobacterium nucleatum and Bacteroides fragilis were associated with resistant disease and poorer outcomes. Gut microbiota was also found to be associated with surgical outcomes and seems to play a significant role in anastomotic leak (ATL) after surgery mainly by collagen breakdown. However, this research field is just at the beginning and the current findings are not yet ready to change clinical practice.

KEYWORDS:

• Gut microbiota
• cancer therapy
• predictive biomarkers
• cancer outcomes
• anastomotic leak

Acknowledgments

KE is supported by The Cancer Biomarkers Working Group. For transparency and scientific publishing ethics, we supported our manuscript by the Turnitin® report of plagiarism (Supplemental material 1). For post-publication peer-review and continuous discussion of this subject, we have created a project on ResearchGate social network and we encourage the readers to ask questions and comment on the topic following this link: https://www.researchgate.net/project/Exploring-the-Impact-of-Gut-Microbiota-on-Survival-and-Therapy-Response-in-Patients-with-Cancer. Authors’ contribution: KE received the invitation for review writing, searched the literature, collected the findings of included studies and related reviews, discussed the topic, and wrote the manuscript. RJ summarized the role of microbiota in ATL. HB summarized the role of diet in GMD. DT commented on the ongoing clinical trials using gut microbiota as a biomarker to predict outcomes and provided help for proof-reading. Professors MA, SA, MB, AM, and Dr. BOAB supervised the article writing and revised the manuscript. All the authors approved the final draft of the paper, for the submission.

Box 1. Recommended reading.

Box 2. Potential laboratories, organizations, and research teams working on gut microbiota and cancer.

Article highlights

• A new wave of biomedical research is focusing on the role and implications of previously neglected factors affecting tumor behavior, namely the microbiota.

• The growing evidence on the role and modulation of commensal gut microbiota in cancer and the relevance of dysbiosis is increasingly enlightened in cancer care.

• The implications of gut microbiota composition have been identified in surgical and systemic treatments, including chemotherapy and immune-checkpoint blockade.

• To date, most of conducted studies on the impact of gut microbiota dysbiosis on cancer outcomes are exploratory in nature with small sample size.

• The methods and techniques used to study gut microbiota have several limitations that may give biased findings.

• Implementing gut microbiota in clinical care needs critical appraisal of current evidence which is still not mature enough to provide guidelines for practice.

• The prognostic and predictive value of gut microbiota is under investigation and clinical trials on its manipulations are ongoing.

Declaration of interest

K. El Bari is supported by the Cancer Biomarkers Working Group. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.