The new study is one of the first publications to come out of an international $25 million collaborative project seeking to investigate the role of the microbiome in colorectal cancers.2 However, this field of investigation is still very new and it may take time for basic science discoveries to be translated into clinical interventions for prevention or treatment of colorectal cancers.

 “A significant challenge regarding teasing apart the contribution of the microbiota to cancer risk has been the lack of longitudinal studies with serial sampling of the gut microbiota over time, prior to cancer development,” said Susan Bullman, PhD, assistant member of human biology at Fred Hutchinson Cancer Research Center in Seattle, Washington. “Although microbiome dysbiosis is a feature of gastrointestinal cancers, we do not know when this microbiome dysbiosis arose and whether it is causal, or a consequence of the cancer,” she added.

The microbiome is estimated to be comprised of more than 10,000 microbial species and is sometimes referred to as its own ecosystem with individuals often having marked differences in composition. So, how much can truly be learned by studying the effects of individual microbes in laboratory settings?


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“The bottom line is that we are starting to understand the microbiome a bit better, certain strains seem to put patients more at risk of certain conditions, but I want to stress that these individual findings are not enough — we really need to understand 1 overgrowth of 1 bacteria vs another; what changes with these interactions,” said Dr Hanna.

If pks+E.coli or another bacterial species is confirmed to be genotoxic and their associated signatures found in colorectal cancer, the study authors suggest that manipulation of the microbiome, via antibiotics or other means, might be possible in the future for people who harbor these bacterial species.

“We need to be cautious regarding the use of broad-spectrum antibiotics, as many studies have shown the importance of a diverse gut microbiota in response to cancer treatment, especially immunotherapies. A narrow-spectrum inhibitor, such as a small molecule that may inhibit the colibactin activity of this strain, could be beneficial to patients carrying these pks+E.coli strains,” said Dr Bullman.

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Of added concern is that pks+E.coli is present in a number of commercially available probiotic supplements, with the authors theorizing that this practice could be putting more people at risk by elevating levels of DNA damage in their gastrointestinal tracts, and hence risk of developing colorectal cancer.

“Over the past decade there have been numerous compelling studies demonstrating the association of pks E. coli with colorectal cancer and the ability of colibactin to induce DNA damage in mammalian cells. I certainly think an extensive review of probiotics containing pks E. coli strains is warranted and where possible determine if there is any correlation between patient populations taking such probiotics and increased incidence of colorectal cancers,” said Dr Bullman.

The microbiome is a popular area of study currently, with investigations ranging from how the microbiome contributes to mental health to how it could shape response to immunotherapy and other oncology drugs. But experts warn that although microbiome studies could advance understanding and have the potential for clinical translation, the field is still in its infancy.

“The problem currently is, all of these bacteria interact in complex networks — [so] identifying the effects of single bacteria is just a small part of the puzzle. It will take a time to understand what all of these interactions mean and how we can alter these to effect clinical outcomes,” said Dr Hanna.

References

  1. Pleguezuelos-Manzano C, Puschhof J, Huber AR, et al. Mutational signature in colorectal cancer caused by genotoxic pks E. coli. Nature. 2020;580(7802):269-273.
  2. Cancer Research UK. Manipulating the microbiome to beat bowel cancer. https://www.cancerresearchuk.org/funding-for-researchers/cancer-grand-challenges/Manipulating-the-microbiome-to-beat-bowel-cancer. Accessed April 20, 2020.