Routine Colonoscopies Might Not Be Necessary

Colorectal cancer is the second leading cause of cancer deaths worldwide, but it can be treatable when caught early. Unfortunately, many people delay diagnosis because colonoscopies, the main screening method, are often expensive and uncomfortable. Those barriers have created a need for better, less invasive ways to detect and understand the factors contributing to colorectal cancer, including the role of gut microbes. 

While recent advances in technology have made it easier to study gut microbes, most methods only identify them at the species level, missing key differences between strains within the same species. These differences can impact how microbes function and interact with our health, making it harder to link them to diseases like colorectal cancer.

To address this, researchers focused on subspecies-level analysis, which examines groups of strains within a species that share specific traits or functions and may be linked to colon cancer. This approach provides a clearer and more detailed understanding of the microbiome’s role in health and disease, capturing variations that species-level analysis often overlooks. These results were published in Cell Host & Microbe. Let’s break them down.

How Was This Study Conducted?

To better understand how gut bacteria influence health and disease, researchers created the HuMSub catalog, a resource that organizes gut bacteria at the subspecies level. Unlike traditional methods that group all strains of a species together, the HuMSub catalog identifies smaller, more precise groups of bacteria, called operational subspecies units (OSUs), that share specific traits or functions. This approach captures key variations that species-level analysis often misses, offering a clearer and more detailed picture of the microbiome’s role in health.

To build the catalog, researchers analyzed a large database of gut bacterial genomes, carefully removing incomplete or contaminated data. They grouped bacteria into operational subspecies units by clustering their genetic coding sequences, focusing on differences that could lead to distinct traits. This method worked across diverse populations, ensuring the catalog captured globally consistent subspecies while highlighting unique characteristics. Using data from colorectal cancer studies, the researchers identified subspecies linked to the disease.

What Did The Study Find?

This study uncovered that bacterial subspecies in the human gut microbiome hold critical information that is often missed when only looking at the species level. Think of it like this: while two strains of bacteria might belong to the same species, they can behave very differently, sort of like siblings with completely different personalities. 

By analyzing a massive database of gut bacteria, researchers identified over 5,000 subspecies across nearly 1,000 species and found that 28% of these species had significant subspecies-level differences. These differences could play a big role in health and disease, but they’ve been overlooked in past research that only focused on species as a whole.

The researchers developed a new method to measure relevant subspecies using unique genetic markers. This method was not only highly accurate but also faster and more efficient than existing tools. When they applied this approach to colorectal cancer studies, they found 218 subspecies linked to the disease. 

In some cases, only one subspecies within a species was associated with colorectal cancer, while its sibling subspecies or parent species was not. For example, one subspecies of Fusobacterium animalis was strongly linked to colorectal cancer, while another closely related subspecies was not. This helps explain why some studies have reported conflicting results when only looking at the species level; important details were being missed.

The study also revealed how genetic differences between subspecies might directly impact health. By identifying these subspecies and their unique characteristics, the research provides a clearer path toward more accurate colorectal cancer diagnostics and targeted treatments, offering hope for earlier detection and better outcomes. Stool samples could play a key role in this process, allowing researchers to non-invasively identify CRC-associated microbes and their subspecies-level traits.

This study provides important insights, but there are a few limitations to keep in mind. Some non-functional gene fragments, called pseudogenes, might have been mistakenly identified as functional genes, though the researchers estimate this affects less than 0.13% of genes. The way genome quality was measured is solid but not yet a standard method in the field. Lastly, some technical limitations in analyzing global subspecies may have caused a few to be missed, meaning their prevalence could be slightly underestimated. Even with these challenges, the study’s findings are still reliable and meaningful.

How Does This Apply To Real Life?

Understanding the gut microbiome at the subspecies level could revolutionize how we approach diseases like colorectal cancer. Why does this matter? Because it opens the door to non-invasive, affordable and accessible diagnostic tools, like stool tests, that could replace or complement uncomfortable procedures like colonoscopies. 

Early cancer detection is critical for survival, and this research brings us closer to identifying specific bacterial subspecies that signal the presence of colorectal cancer, potentially catching it before symptoms even appear.

Beyond diagnostics, this deeper understanding of gut bacteria could lead to more targeted treatments. If certain subspecies are found to contribute to cancer progression, therapies could be developed to neutralize or modify their behavior. This means we’re not just talking about better detection but also personalized approaches to treatment that could improve outcomes and save lives. 

For anyone concerned about cancer or looking for less invasive healthcare options, this research is a step toward a future where gut health plays a central role in disease prevention and care. Currently, current guidelines from organizations like the American Cancer Society recommend colonoscopies for adults starting at age 45, but stool-based tests are often suggested as an alternative for those at average risk or unable to undergo a colonoscopy.

Our Expert Take

This study published in Cell Host & Microbe highlights a groundbreaking step forward in understanding the gut microbiome and its connection to colorectal cancer. By focusing on subspecies-level analysis, researchers uncovered critical differences within bacterial species that could influence health and disease. They identified over 5,000 subspecies, including 218 linked to colorectal cancer, and developed a method to measure these subspecies with high accuracy. Importantly, this research shows that stool samples may be used to detect these subspecies, offering a non-invasive and accessible alternative to traditional screening methods like colonoscopies to identify colon cancer risk.