Colorectal cancer used to be considered a disease of the aged, but rising rates among younger adults have left physicians and scientists scratching their heads. Now, a new study hints that populations of gut bacteria might be playing a role.
In a study published Feb. 5 in EBioMedicine—a sub-publication of The Lancet—researchers from the Cleveland Clinic shared data indicating young patients’ tumors have distinct bacteria profiles compared to older ones. The findings could be used to identify new diagnostic markers as well as to inform treatment strategies, the scientists said.
“By detailing this microbial signature of young-onset disease, we can look toward new screening biomarkers and drugs targeting related bacteria,” Shimoli Barot, M.D., first author of the paper, said in a press release.
To conduct the study, the researchers used tumor and unaffected colorectal tissue samples from 276 colorectal cancer patients who underwent surgical treatment at the Cleveland Clinic. The patients were split roughly evenly between those who were younger than 50 when they were diagnosed and those who were over 60, as well as between males and females within each group.
Curious to identify any differences in the tumor microbiomes between the two groups—a hypothesis informed by previous studies showing that bacteria in the intestine might be players in colorectal cancer development—the researchers used DNA extraction and RNA sequencing to profile the bacteria populations in the tumor samples. The results showed that younger patients’ microbes were “significantly more diverse and unique” than older ones, both in the tumor and in non-tumor tissue.
Two bacteria in particular, akkermansia and bacteroides, were more common in the younger cohort, while older patients’ tumors had higher levels of bacillus, staphylococcus, listeria, enterococcus, pseudomonas, fusobacterium and escherichia/shigella. Akkermansia has been called a “promising next generation probiotic” for its ability to regulate immune and metabolic function and is currently sold over the counter, while bacteroides are gram-negative bacteria with more complicated health effects.
Other factors influenced the microbe populations, too, and these were also stratified by age. Tumors in the rectum had different bacterial profiles than those in the colon, and patients who were classified as medically overweight or obese, based on their BMI, had different bacteria than those who had a normal BMI. The bacteria even differed based on whether the tumors were on the patient’s right or left side. A history of tobacco use, however, didn’t lead to a difference in microbial profiles between young and old patients.
Finally, the researchers found that in young patients, a greater amount of akkermansia was linked to a longer overall survival, and that young patients in stages 1 through 3 of the disease—considered early stage—had larger populations of bacteroides in the tumors compared to the primary tumors of stage 4 patients.
“These distinct behaviors of the akkermansia and bacteroides [families] in young-onset colorectal cancer dysbiosis suggest important directions for future studies,” the study authors wrote in their article.
The different populations of bacteria in tumors could influence treatment outcomes, the scientists noted, as evidenced by studies on different types of cancer. For example, immune checkpoint inhibitors seem to work better in small cell lung or renal cancer patients whose tumors have “an abundance of akkermansia,” they wrote, adding that “the potential implications of such therapies [in young colorectal cancer patients] need further exploration.”