Changing the paradigm: Microbiome modulation may become the next ‘pillar’ in cancer treatment

13-Apr-2021 - Last updated on 28-Apr-2021 at 07:44 GMT

Insights have been gained into the role of the microbiome in disease states such as cancer, and strategies to manipulate the microbiome are quickly emerging, though optimal approaches are not yet known, said experts during an AACR 2021 event this week.

The field offers great promise. Additional research in this space is critically needed, however.

“There is an element of hype, which needs to be tempered, and there is also tremendous hope and opportunity in modulating the microbiome,” said Dr Jennifer A Wargo, the University of Texas MD Anderson Cancer Center.

She moderated the symposium, The Microbiome in Cancer Therapy: Hype or Hope? yesterday [April 12] as part of the American Association of Cancer Research (AACR) meeting 2021.

There is a growing appreciation of the role of microbes in health and disease, and characterization of microbes and their genomes, collectively referred to as the microbiome, has been made easier by the use of next-generation sequencing, said the speakers.

Data is beginning to show that changes in both tumor and gut microbiomes can play a role in the success or failure of cancer therapies, they said.

Preclinical and clinical studies have shown that modifying the microbiome can positively, or negatively, affect response to cancer therapy, they noted.

Influence of the gut on health and disease

A typical adult human body contains about 30 trillion human and 39 trillion microbial cells, said Dr Rob Knight, the Center for Microbiome Innovation at the University of California, San Diego.

Each person has 20,000 human genes and up to 20 million microbial genes. Until recent years, cancer research turned a blind eye to our microbial selves, he added. “We are ignoring the 99% of our genes that we can change, our microbial genome. What happens in the gut affects health and disease throughout the body, including cancers.”

Microbes are involved in most hallmarks of cancer and in most types of cancer, Knight commented. Bloodborne microbial DNA is strongly predictive for the 33 cancer types included in the Cancer Genome Atlas (TCGA), the landmark cancer genomics program, he added.

Clinical trials, he continued, have shown that modifying the gut microbiome can change immunotherapy response.

Microbial biomarkers

Microbial species can also serve as biomarkers for cancer and other diseases.

Microbes are already being used as therapeutic agents in fecal microbial transplantation (FMT), and personalized microbial therapeutics are on the horizon. Indeed, at least 20 microbial biomarkers for colorectal cancer (CRC) have already been identified, said Dr Siew C. Ng, who is based at the Microbiome I-Centre, the Chinese University of Hong Kong.

Altering the microbiome can change the efficacy of multiple cancer therapies, convert non-responders into responders, reduce treatment-associated toxicity, and influence survival, she argued.

A diverse microbiota rich in Akkermansia, Bifodobacterium, Faecalibacterium and certain other species predicts response to cancer immunotherapy. And the use of antibiotics shortly before or during immunotherapy inhibits immunotherapy response in patients with non-small cell lung cancer, renal cell carcinoma, and melanoma.

“We now know that bacterial-mediated interactions with the immune system are essential for optimal drug efficiency. The right microbiome can create a favorable tumor microenvironment to overcome cancer and treatment resistance,” said Ng.

The mechanistic links between microbiome and clinical outcomes remain murky though. After more than 600 FMTs and multiple clinical trials, it appears that multiple elements of bacterial, fungal, and viral microbiota play roles in modifying response to disease and treatment response, she added.