The Microbiome and Cancer: Is the 'Oncobiome' Mirage Real?

Abstract

Investigations focused on the interplay between the human microbiome and cancer development, herein termed the 'oncobiome', have been growing at a rapid rate. However, these studies to date have primarily demonstrated associative relationships rather than causative ones. We pose the question of whether this emerging field of research is a 'mirage' without a clear picture, or truly represents a paradigm shift for cancer research. We propose the necessary steps needed to answer crucial questions and push the field forward to bring the mirage into a tangible reality.

Figure 1. Proposed Oncobiome Studies Necessary to Progress the Field of Research

Cancer subjects (gray) or healthy subjects (white) are presented for each area of needed investigation. (A) Cancer-associated microbiota (yellow) is transmitted to mice with humanized immune systems to investigate their interaction with the human immune system and their ability to cause cancer. (B) Patients at high risk or with a genetic predisposition to cancer are treated with microbiota replacement therapy to restore eubiosis (blue). Patients are compared to the general population and control subjects not treated with microbiota replacement therapy for differences in cancer incidence. (C) The microbiota of cancer patients are screened for known carcinogenic molecules and genes. Candidates are identified and tested in vivo for their ability to cause cancer formation. (D) The microbiota of cancer patients are determined before and after standard cancer treatment. Determination is made regarding restoration of eubiosis and if continued or recurrent dysbiosis is associated with cancer recurrence. (E) The microbiota of healthy subjects are determined prospectively and correlated with the development of precancerous and cancerous lesions. (F) The microbiota of healthy individuals are determined for various organ systems and body fluids. This will prove crucial for future investigations and to determine if body fluids/specimens from one site can act as a surrogate for a different disease site.

Figure 2. Hypothetical Integration of the Oncobiome into the Care of Cancer Patients

Each area is divided into screening, treatment, and surveillance phases. Each phase characterizes the microbiota of the patient based on the cancer to be screened/treated (i.e., feces for CRC). Treatment is based upon tested regimens that have demonstrated efficacy with a particular microbiota or metabolite profile. It can be envisaged that patients who have restoration of eubiosis will have improved cancer survival compared to those who maintain or relapse to dysbiosis after treatment.