3D Rendered Medical Illustration of Male Anatomy showing Colorectal Cancer (© SciePro - stock.adobe.com)
CLEVELAND — Colorectal cancer rates are rising at an alarming rate among young adults, but the reason behind the increased diagnoses has been a medical mystery. However, the Cleveland Clinic has released a study that pinpoints a major cause for the spike in cases: diet.
When looking at the microbiomes of adults 60 years and younger with colorectal cancer, researchers found an unusually high level of diet-derived molecules called metabolites. The metabolites involved in colorectal cancer usually come from eating red and processed meat.
“Researchers—ourselves included—have begun to focus on the gut microbiome as a primary contributor to colon cancer risk. But our data clearly shows that the main driver is diet,” says Dr. Naseer Sangwan, a director at the Microbial Sequencing & Analytics Resource Core at the Cleveland Clinic and study co-author, in a media release. “We already know the main metabolites associated with young-onset risk, so we can now move our research forward in the correct direction.”
The study is published in the journal npj Precision Oncology.
The researchers created an artificial intelligence algorithm to examine a wide range of datasets in published studies to determine what factors contributed most to colorectal cancer risk. One crucial area to explore was the gut microbiome. Previous research showed significant differences in gut composition between younger and older adults with colorectal cancer.
One of the most striking features among young adults and older adults with colorectal cancer is the differences in diet, reflected through the type of metabolites present in the gut microbiome. Younger people showed higher levels of metabolites involved in producing and metabolizing an amino acid called arginine, along with metabolites involved in the urea cycle.
According to the authors, these metabolites likely result from overeating red meat and processed foods. They are currently examining national datasets to confirm their findings.
Choosing between the two, it is much simpler to change a diet than to completely reset a person’s microbiome. The findings suggest that eating less red and processed meat could lower a person’s risk of colorectal cancer.
“Even though I knew before this study that diet is an important factor in colon cancer risk, I didn’t always discuss it with my patients during their first visit. There is so much going on, it can already be so overwhelming,” says Dr. Suneel Kamath, a gastrointestinal oncologist at the Cleveland Clinic and senior author of the study. “Now, I always make sure to bring it up to my patients, and to any healthy friends or family members they may come in with, to try and equip them with the tools they need to make informed choices about their lifestyle.”
Making healthier dietary choices is also a more accessible method for preventing colorectal cancer. While screening is an important tool, Dr. Kamath notes it is impractical for doctors to give every person in the world a colonoscopy. In the future, simple tests that count specific metabolites as a marker for colorectal cancer risk may help with increased monitoring. On the research side, the authors plan to test whether particular diets or drugs involved in regulating arginine production and the urea cycle can help prevent or treat colorectal cancer in young adults.
Paper Summary
Methodology
The researchers collected blood and tissue samples from 64 people with colorectal cancer (CRC), dividing them into two groups: 20 patients with early-onset CRC (diagnosed at age 50 or younger) and 44 with average-onset CRC (diagnosed at age 60 or older). They also included a control group of 49 people without cancer.
They analyzed these samples in two ways:
- Metabolomics: They looked at over 400 metabolites (small molecules) in the blood using a technique called gas chromatography-mass spectrometry.
- Microbiome analysis: They examined the bacterial communities in the tumor tissue using DNA sequencing.
The researchers then used advanced statistical methods and machine learning to identify differences in metabolites and bacteria between early-onset and average-onset CRC, look for correlations between specific metabolites and bacteria, and build models that could distinguish between early-onset and average-onset CRC based on these profiles.
Key Results
The metabolite profiles in blood were much better at distinguishing early-onset from average-onset CRC compared to the bacterial profiles from tumor tissue. Researchers identified several metabolites and bacterial species that were different between the two groups.
Glycerol and pseudouridine were more abundant in average-onset CRC. Certain bacteria like Parasutterella and Ruminococcaceae were more common in early-onset CRC.
Researchers also found interesting correlations between certain metabolites and bacteria. For instance, glycerol and pseudouridine were negatively correlated with the bacteria more common in early-onset CRC. Network analysis showed different patterns of interaction between metabolites and bacteria in early-onset vs. average-onset CRC, particularly involving urea cycle metabolites.
Study Limitations
The study only included 64 CRC patients, which limits its statistical power and generalizability. The findings weren’t tested in a separate group of patients to confirm their accuracy. Samples were collected after cancer diagnosis, so it’s unclear if the observed differences caused the cancer or resulted from it.
While the researchers tried to account for some factors, there could be unmeasured variables influencing the results. Only tumor tissue was analyzed, not stool samples, which might provide a more complete picture of gut bacteria.
Discussion & Takeaways
Blood-based metabolite profiles show promise as a potential biomarker for distinguishing early-onset from average-onset CRC. The study highlights the complex interplay between metabolism, gut bacteria, and cancer development in younger vs. older patients. Differences in urea cycle metabolism between early-onset and average-onset CRC could be an important area for further research, potentially leading to new therapeutic approaches.
The findings suggest that the biological processes underlying early-onset CRC may be distinct from those in older patients, which could have implications for prevention, screening, and treatment strategies. While promising, these results need to be validated in larger, diverse populations before they can be applied clinically.
Funding & Disclosures
The study was supported by the Sondra and Stephen Hardis Chair in Oncology Research.
Several authors reported potential conflicts of interest, including:
- Consulting roles for pharmaceutical and biotech companies
- Research funding from various sources
- Equity stakes in healthcare-related companies
- Speaking honoraria
These disclosures are important for transparency, allowing readers to consider any potential biases in the research or its interpretation.
It’s more the processed meat than a good ole T-Bone. Everything is processed today. Just a back hand way to get people to eat less red meat, you know, warming & everything.