What is already known
Colorectal cancer accounts for 10% of cancer cases and nearly a million deaths every year. Gut microbes play a key role in colorectal cancer by influencing inflammation, with previous research suggesting the microbiota can suppress or promote cancer progression depending on inflammation levels. However, the mechanisms behind its protective effects remain unclear.
What this research adds
Working in mice, researchers found that the gut microbiota suppresses a gene called Snhg9, which promotes tumor growth. Antibiotics depleted the microbiota, leading to increased Snhg9 expression. The human version of Snhg9 appears to function similarly to the mouse version.
Conclusions
The findings suggest that the microbiota plays a protective role against colorectal cancer by regulating Snhg9.
Colorectal cancer accounts for 10% of cancer cases and nearly a million deaths every year. Now, a study done in mice suggests that the gut microbiota plays a protective role against colorectal cancer by regulating a gene that promotes tumor growth.
The findings, published in Developmental Cell, highlight the complex relationship between the gut microbiota, inflammation, and colorectal cancer, indicating that a healthy microbiota may help prevent tumor progression.
Scientists have known that gut microbes play a key role in colorectal cancer by influencing inflammation, with previous research suggesting the microbiota can suppress or promote cancer progression depending on inflammation levels. For example, while antibiotics can reduce inflammation associated with colorectal cancer in some cases, these drugs are linked to higher risk of colorectal cancer when overused, likely due to their impact on beneficial gut bacteria. However, the mechanisms behind the microbiota’s protective effects remain unclear.
Working in mice, researchers led by Meng Wang at Zhejiang University School of Medicine in China set out to explore the impact of the gut microbiota on colorectal cancer progression.
Tumor protection
First, the researchers gave mice a substance that induced mild colon inflammation, which in turn leads to colorectal cancer. Then, they treated some of the mice with antibiotics. Animals that received antibiotics had larger, more numerous tumors and worse tissue changes than mice that didn’t receive antibiotics. This finding confirms that gut bacteria play a protective role in preventing colorectal cancer under mild inflammatory conditions, the researchers say.
Further experiments showed that the gut microbiota suppresses a gene called Snhg9, which promotes tumor growth. When antibiotics deplete the microbiota, Snhg9 expression increases, boosting tumor progression.
Despite having low sequence similarity, the human and mouse versions of Snhg9 are functionally conserved, both promoting tumor growth. Like its mouse counterpart, human Snhg9 increased cell proliferation and tumor development, the researchers found.
Antibiotics risk
Overexpressing human Snhg9 in mice disrupted the protective effects of the gut microbiota against colorectal cancer, the team also found. This suggests that human Snhg9 is an important factor in microbiota-regulated cancer progression.
The findings also indicate that while antibiotics are effective in reducing inflammation associated with colorectal cancer, their use may increase cancer risk by disrupting the gut microbiota. Long-term antibiotic use can also lead to infections with pathogens such as Clostridioides difficile, further increasing susceptibility to colorectal cancer, the researchers say.
“Although our study identifies a conserved mechanism by which Snhg9 promotes tumorigenesis in both mouse and human [colorectal cancer] models, the direct relevance of these findings to human disease remains to be fully established,” they add. “Further research involving human tissue samples and clinical data is needed to validate this mechanism in the context of human [colorectal cancer].”
