The role of microbes that live on human surfaces — generally referred to as microbiota – in cancer formation, diagnosis, prognosis, and treatment have long been disputed.[1]. However, researchers agree that microbial communities, formed by bacteria, archaea, fungi, protozoa and viruses interact with our own physiology and are known to play important roles in human health and disease.[1]

Furthermore, recent studies have claimed that a select number of bacteria, viruses, and/or fungi are pervasive among cancers, are key actors in cancer immunotherapy, and can be engineerable to treat a variety of cancers. As a result, the study of the microbiome has, over the last decade, become an expansive area of research. [2]

Microbiota such as biofilms confer bacteria and genetic changes critical to tumor development. Credit: Graphic courtesy of Nature Cancer

‘Oncomicrobes’
Despite these findings, the number of ‘oncomicrobes’ known to directly cause carcinogenesis remains relatively small, with only 11 species labeled as such by the International Association of Cancer registries []. Nevertheless, these carcinogenic oncomicrobes account for approximately 2.2 million new cancer cases each year, translating in a non-negligible 13% of all newly diagnosed cancer cases per year.

However, only a few associations have really garnered support from the scientific community, such as hepatitis B and C affiliated with development of liver cancer, studies describing microbiota’s disease-causing and therapeutic contributions with many cancers are still very much in the early stages.[4]

Beyond the direct link between these ‘oncomicrobes’ and cancer, researchers believe that there are several indirect roles that may play a much larger role in the development of cancer. Initial have suggested that these indirect roles of so-called ‘complicit’ microbes, mediated by intricate relationships between microbial communities and the relevant tissue. can either promote or inhibit the development of cancer. [1]

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Specific bacteria
In a review article published in the July 31, 2023 edition of Nature Cancer, three infectious diseases and cancer experts from the Johns Hopkins Kimmel Cancer Center, the center’s Bloomberg~Kimmel Institute for Cancer Immunotherapy  and the Johns Hopkins University School of Medicine, share their insights into the mechanisms by which specific bacteria, or their communities, contribute to carcinogenesis.

They also discuss the bidirectional interplay between microbiota and host gene or epigenome signaling.[4]

More research needed
Comprehensive studies are needed to further understand how the microbiome is driving some of the biology underlying cancer development and cancer responses to treatment, the authors say.

“We’re at a point in the field of microbiome studies as they relate to cancer where there’s now a large body of data showing associations, and a smaller amount of data showing mechanisms and direct effects promoting tumor development, but there are more questions than answers,” noted study co-author Jessica Queen, M.D., Ph.D., an assistant professor of medicine at Johns Hopkins.

“We focused our review on what we know now and the remaining critical gaps to move forward,” Queen said.

The paper reviewed published studies in areas such as biofilms and other mechanisms promoted by the microbial community, microbes as modulators of the immune system, microbiota metabolites that potentially contribute to cancer development, the impact of diet as a modifier of metabolites, microbiota effects on the host genome and microbiota modulation as therapy for cancer, such as the use of human fecal microbiota transplantation (FMT), prebiotics and probiotics.

Several hurdles need to be overcome to advance the field, the authors say. One is inconsistency between some studies of microbes that have been associated with certain cancers or therapeutic modalities, likely caused by technical differences in DNA extraction or sequencing practices. Another is the gaps between computational or mouse models and translation to humans, with few rodent studies validated in humans.

Investigators in the field have been quick to publish their work, adds study co-author Cynthia Sears, M.D., Bloomberg~Kimmel Professorship of Cancer Immunotherapy and professor of medicine. Two FMT studies, for example, generated intense interest, but only two patients responded well to the therapy among 25 given FMT.

“It’s time to settle down and have a more comprehensive, prospective, thoughtful plan to understand what matters, such as through longitudinal, well controlled human studies incorporating microbiome science,” says Sears, who is also the microbiome program leader at the Bloomberg~Kimmel Institute for Cancer Immunotherapy and a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health.

“Expanding the scope of new clinical trials is one approach to speed the development of improved insights and, ultimately, tools to prevent, diagnose and treat cancer,” Sears added.

Bacterial function is an area on which there could be more focus, adds co-author Fyza Shaikh, M.D., Ph.D., an assistant professor of oncology at Johns Hopkins. “The metabolites offer an opportunity to focus on the output of an entire bacterial community and identify any redundancies that might be present between different bacteria that might do the same thing,” Shaikh says.

“That has really been inconsistent across a lot of current studies,” Shaikh concluded.

According to the authors, future studies should focus on collecting clinical data, including about dietary and medication exposures as key modulators of the microbiome.

Reference
[1] Gabaldón T. Roles of the human microbiome in cancer. Hepatobiliary Surg Nutr. 2021 Aug;10(4):558-560. doi: 10.21037/hbsn-21-241. PMID: 34430543; PMCID: PMC8351001.
[2] Sepich-Poore GD, Zitvogel L, Straussman R, Hasty J, Wargo JA, Knight R. The microbiome and human cancer. Science. 2021 Mar 26;371(6536):eabc4552. doi: 10.1126/science.abc4552. PMID: 33766858; PMCID: PMC8767999.
[3] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt B):1-441. PMID: 23189750; PMCID: PMC4781184.
[4] Queen J, Shaikh F, Sears CL. Understanding the mechanisms and translational implications of the microbiome for cancer therapy innovation. Nat Cancer. 2023 Aug;4(8):1083-1094. doi: 10.1038/s43018-023-00602-2. Epub 2023 Jul 31. PMID: 37525016.

Featured image: Hepatitis B Virus; Colorized transmission electron micrograph of hepatitis B virus particles (colorized pink). This transmission electron micrograph (TEM) revealed the presence of hepatitis B virions. The large round virions are known as Dane particles.  Hepatitis means inflammation of the liver. Toxins, certain drugs, some diseases, heavy alcohol use, and bacterial and viral infections can all cause hepatitis. Hepatitis is also the name of a family of viral infections that affect the liver; the most common types in the United States are hepatitis A, hepatitis B, and hepatitis C.<p>Hepatitis B is caused by infection with the Hepatitis B virus (HBV). The incubation period from the time of exposure to onset of symptoms is 6 weeks to 6 months. HBV is found in highest concentrations in blood and in lower concentrations in other body fluids (e.g., semen, vaginal secretions, and wound exudates). HBV infection can be self-limited or chronic. 1981 Dr. Erskine Palmer.Photo courtesey: NIAID and CDC (Transmission electron micrograph image courtesy of CDC; colorization by NIAID).


How to Cite

DOI: https://doi.org/10.14229/onco.2023.09.18.010

Peter Hofland, Ph.D 1
Understanding the True Impact of Microbiota on Cancer Development and Treatment – Onco Zine – The International Oncology Network, September 12, 2023.
DOI: 10.14229/onco.2023.09.18.010
1 Sunvalley Communication, LLC / Onco’Zine


 

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