With the rise of pop culture’s interest in gut health, the microbiome has taken center stage. Simply put, the microbiome refers to all bacterial cells living inside the gastrointestinal tract. When the gut microbiome is out of whack, there is an imbalance of good bacteria versus bad bacteria. This imbalance can be caused by a variety of factors like diet, medicines, stress, and disease, among others. Many scientists around the world are avidly studying the microbiome to uncover health insights.

We connected with Drs. Michael G. White and Nadim Ajami from The University of Texas MD Anderson Cancer Center to help us understand the role of the gut microbiome, and more specifically, its role in colorectal cancer.

The Gut Microbiome – What Is It?

The gut microbiome is a complex environment of bacteria, viruses and fungi comprising the vast majority of genetic diversity within each person – well beyond an individual’s own DNA1-6. Increasingly well-defined, the gut microbiome has been linked with a myriad of health conditions. These interactions are now understood to occur both locally (in the gut) and systemically (with impact throughout the body) through changes in the immune system among other mechanisms. The gut microbiome’s local proximity to the colon led many early investigators to study its impact on colorectal cancers (CRC), placing CRC at the forefront of studies in the microbiome’s influence on cancer development, progression, and response to therapy.

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How Does the Gut Microbiome Connect to Colorectal Cancer?

While CRC incidence and mortality have decreased over recent years, its increase in young adults has prompted a deeper examination of factors affecting the gut microbiome, such as environmental exposures and diet. A variety of studies have demonstrated an imbalance in the microbiome of CRC patients, including a disproportionate amount of bacteria linked to pro-tumor microenvironments7,8, DNA damage9,10, and modulation of short chain fatty acids within the gut that may act as protective agents for cancers11,12[DRB1] [MW2] . CRC cancers themselves also demonstrate an increased diversity of viruses [DRB3] in their microbiome13,14. Whether this is connected to the imbalance of gut bacteria in cancer patients or they are related to cancer development [DRB4] is an area of active investigation.

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What Does This Mean for the Future of Colorectal Cancer Care?

Recent findings have the potential to benefit CRC patients and the general population in the near future. Specific microbial species, metabolites, and alterations are being investigated and validated as strategies for cancer interception, treatment and prevention.

Carefully controlled trials to modulate the microbiome via fecal transplanatation are underway to measure the impact of shifting the composition and structure of the gut microbiome. Early data from melanoma patients demonstrates that fecal transplantation can induce a response to immunotherapy in patients who initially were resistant to immunotherapy.

Microbial markers of disease progression (genetic material of bacteria and viruses, other proteins, or metabolites) may also improve surveillance and treatment strategies. A future microbial signature could potentially act as a marker for risk of development of metastatic CRC measured using a simple blood draw15,16. This could help doctors decide when to prescribe adjuvant chemotherapy and influence the development of future therapeutics.

Lastly, microbial markers of CRC hold promise for fine-tuning cancer screening guidelines for the general public. Given the rising rates of CRC in young adults, the percent of the population for whom screening is recommended continues to increase. However, due to a limited number of endoscopists in the U.S., there is a need for improvement of risk assessment tools. Gut microbial insights could generate more effective screening methods, while also making sure those at the highest risk receive the screening they need.

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What are some key takeaways for patients concerned about their microbiome health?

Microbiome profiling is not akin to glucose or blood pressure measurements, where a single number defining “healthy” can be applied to the general population. Moreover, its complex interactions affect a variety of health conditions in different ways – therefore, an “ideal” gut microbiome for any given condition is not fully defined. Your microbiome should only be studied under the direction and guidance of your medical team. Direct-to-consumer profiling services (kits you can buy from online and box stores) do not offer appropriate medical follow-up and guidance. To ensure your microbiome is functioning in the healthiest capacity, the best advice to date is the simplest: follow a diverse, high-fiber diet (as medically able), avoid probiotic supplements (unless recommended by your physician), and only make changes after directed discussion with your physician.

Microbiome Research

Lee Jones, a stage IV survivor and research advocate, was one of 10 research advocates from five countries selected to participate in the OPTIMISTICC study, a project investigating the relationship between the human microbiome and CRC. It is funded by a five-year grant from Cancer Research UK as part of their Cancer Grand Challenges program (now in partnership with the U.S. National Cancer Institute).

“This research tends to be mostly lab-related and it requires a much heavier knowledge of science than I have, but research advocates have played an important role. We have helped relate the lab findings to the real world so patients find more potential value. Also, dietary information and tumor, blood, and stool samples are collected at several points during participants’ chemotherapy or immunotherapy treatments. We have provided valuable input regarding this as well.

Findings of the study have so far demonstrated strong associations between several microbes and CRC. One of the studies, headed by Dr. Kimmie Ng at Dana-Farber, is looking specifically at the role the microbiome may play in young onset colorectal cancer. One of the more interesting findings is of a predatory bacterium that only attacks one of the cancer-associated microbes. We don’t know how this might play out in the human body, but it’s amazing to watch the attack under a microscope!”

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Food. We can't live without it, but for many in the colorectal cancer community, it's hard to live with it. Yet as doctors, nutritionists, and research data all say: Diet and nutrition play an essential role in cancer prevention and treatment. Food is a topic we can't ignore.

Authors

Michael G. White, MD| Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Nadim Ajami, PhD | Program for Innovative Microbiome and Translational Research (PRIME-TR), The University of Texas MD Anderson Cancer Center, Houston, TX, USA

References
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  2. Goodrich JK, Waters JL, Poole AC, et al. Human genetics shape the gut microbiome. Cell. 2014;159(4):789-799.
  3. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222-227.
  4. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-563.
  5. Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474(7351):327-336.
  6. Falony G, Joossens M, Vieira-Silva S, et al. Population-level analysis of gut microbiome variation. Science. 2016;352(6285):560-564.
  7. Bullman S, Pedamallu CS, Sicinska E, et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017;358(6369):1443-1448.
  8. Hamada T, Zhang X, Mima K, et al. Fusobacterium nucleatum in Colorectal Cancer Relates to Immune Response Differentially by Tumor Microsatellite Instability Status. Cancer Immunol Res. 2018;6(11):1327-1336.
  9. Boleij A, Hechenbleikner EM, Goodwin AC, et al. The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis. 2015;60(2):208-215.
  10. Chung L, Orberg ET, Geis AL, et al. Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells. Cell Host Microbe. 2018;23(3):421.
  11. Makki K, Deehan EC, Walter J, Backhed F. The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease. Cell Host Microbe. 2018;23(6):705-715.
  12. Donohoe DR, Holley D, Collins LB, et al. A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner. Cancer Discov. 2014;4(12):1387-1397.
  13. Hannigan GD, Duhaime MB, Ruffin MTt, Koumpouras CC, Schloss PD. Diagnostic Potential and Interactive Dynamics of the Colorectal Cancer Virome. mBio. 2018;9(6).
  14. Nakatsu G, Zhou H, Wu WKK, et al. Alterations in Enteric Virome Are Associated With Colorectal Cancer and Survival Outcomes. Gastroenterology. 2018;155(2):529-541 e525.
  15. Bertocchi A, Carloni S, Ravenda PS, et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell. 2021;39(5):708-724 e711.
  16. Poore GD, Kopylova E, Zhu Q, et al. Microbiome analyses of blood and tissues suggest cancer diagnostic approach. Nature. 2020;579(7800):567-574.

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