Gut Microbiome Changes May Warn of Colorectal Cancer
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People who go on to develop precancerous colon polyps have significant variations in the type and diversity of bacteria in their gut microbiome compared with healthy people, according to new research presented at UEG Week 2023, the annual conference of United European Gastroenterology.
These changes can be detected before the polyps become colorectal cancer, says lead author Ranko Gacesa, PhD, researcher and professor at University Medical Center in Groningen, Netherlands. “If these findings are confirmed, this means that looking at the gut microbiota could improve on current noninvasive fecal tests used to detect and prevent colorectal polyps and cancer,” he says.
How Does This Study Build on Earlier Research?
Prior research has found that certain strains of bacteria and the compounds those bacteria make inside the gut are associated with higher or lower risks of colorectal cancer, according to the American Institute for Cancer Research. But which comes first — that is, whether microbiome changes alter the course of the cancer or if the cancer results in microbiome changes — isn’t completely understood.
Lower Gut Diversity Linked With Precancerous Polyps
To investigate the connection between different bacteria found in the gut and precancerous colon polyps, researchers linked data from over 8,000 participants from the Dutch Microbiome Project with the Dutch nationwide pathology database to identify all recorded cases of colonic biopsies from the last 50 years.
Researchers analyzed the gut microbiomes of people who developed precancerous colorectal lesions before fecal sampling between 2000 and 2015 (214 people), as well as those who developed lesions after fecal sampling between 2015 and 2022 (305 people). Then they compared those gut microbiome findings with the microbiomes of people with normal colonoscopy findings (202 people) and the general population.
Investigators found that individuals with precancerous lesions had reduced gut bacteria diversity compared with healthy individuals.
It’s Still Unclear Why Certain People Have ‘Bad’ Microbes in the Gut
These findings make sense given that, in general, higher microbiome diversity is generally considered to be an indicator of “good” gut health and lower diversity as less desirable, says Dr. Gacesca. “This is based on studies which identified that patients with certain diseases such as inflammatory bowel disease [IBD] have reduced microbiome diversity in the gut,” he says.
Colorectal Polyps Typically Take 5 to 10 Years to Develop
The large number of subjects in the study and the lengthy follow up — researchers were able to follow participants for decades — are both important strengths of this study, says Suneel Kamath, MD, a hematologist and medical oncologist and assistant professor of medicine at Cleveland Clinic in Ohio, who was not involved in the research.
“Following participants for a relatively long period is especially important with colorectal cancer studies because it’s often a 5- to 10-year process to go from a normal colon to a polyp forming, and then forming cancer, and so you really need a pretty substantial period of follow up,” he says.
Bacterial Species Associated With Potential Risk of Colorectal Cancer
“It is known from previous studies that some of the species we identified are linked to the development of colorectal lesions that are potentially genotoxic,” says Gacesca, meaning they cause mutations in cells which may lead to cancer. “For example, Bacteroides fragilis is known to produce toxin which can contribute to chronic low-grade inflammation, and chronic gut inflammation is likely to be genotoxic/carcinogenic,” he adds.
“Another example is Akkermensia species which can degrade gut mucus and thus reduce the capability of the organism to defend against pathogens, again leading to chronic inflammation and potentially cancer,” he says.
Additionally, the analysis found that the bacterial species from the family Lachnospiracea and the genera Roseburia and Eubacterium were linked with the future development of lesions.
But researchers still don’t know why certain people have these “bad” microbes in their guts, says Gacesca. “And there is no clear consensus on the effectiveness of microbiome-altering therapies,” he adds.
Could Probiotics and Prebiotics Help Prevent Colorectal Cancer?
If confirmed, these findings could be used to help point the way to microbiome-targeted therapies, such as fecal microbiome transplants and probiotics and prebiotics. “This would require extensive testing to demonstrate that such probiotics have expected effect,” says Gacesca.
The work of creating these therapies is ongoing, and it is likely we will see advances in the near to mid-term future.
“What’s challenging in the field right now is that which bacteria end up being significant — or not significant — can really vary a lot across different studies. One in particular, Fusobacterium nucleatum, which is a bacterium that exists in the mouth, has been associated with increased risk of a lot of different cancers, including colorectal cancer. I was a little surprised to see that it wasn’t called out specifically in this study,” says Dr. Kamath.
A paper on the growing evidence for a link between Fusobacterium nucleatum and colorectal cancer risk was published in the November 2022 issue of Frontiers in Cellular and Infection Microbiology.
The finding that Roseburia was associated with the development of precancerous polyps was also surprising, says Kamath. “It’s been linked to helping with blood sugar control and weight loss and so it’s often associated with positive factors,” he says.
These conflicting findings highlight the relative newness of so much research on the microbiome and its role in cancer. It is a burgeoning field, says Kamath. “We need a lot more studies to really prove what’s truly going on here,” he adds.
Colorectal Cancer the Third Most Common Cancer
Not including skin cancers, colorectal cancer is the third most common cancer in both men and women in the United States, according to the American Cancer Society. It’s estimated that there will be more than 150,000 new cases of colon and rectal cancers in the United States this year.
It’s recommended that people who are at average risk start regular screening at age 45, either with a stool-based test or a visual exam such as a colonoscopy or virtual colonoscopy.
Risk factors for colorectal cancer include age, heath history, and genetic vulnerabilities, as well as lifestyle-related factors including having overweight or obesity, lack of physical activity, a diet high in processed meats and red meat, smoking, and heavy alcohol use, per the society.
Should You Seek Out Probiotics to Prevent Colorectal Cancer?
Right now, there isn’t enough solid evidence to recommend certain probiotics to reduce the risk of colorectal cancer, says Kamath.
He suggests focusing on known risk factors such as achieving and maintaining a healthy weight. “In the United States, the lack of microbial diversity and poor gut health is driven by overweight and obesity. As we continue to get more data on colorectal cancer concern, that’s increasingly the most concerning risk factor,” he says.
He recommends the Mediterranean diet to his patients who want to reduce their risk. “I’m a big fan of that way of eating, focusing on lean meats, fatty fish, beans, legumes, nuts, fresh fruit, and leafy green vegetables, and limiting processed foods,” he says.
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