Gut Microbes Serve as Indicators of Colorectal Cancer

The abundance of specific types of bacteria in the guts of patients with colorectal cancer could lead to the development of a noninvasive, sensitive clinical diagnostic test for colorectal cancer.

Current screening methods for colorectal cancer include the invasive colonoscopy or less invasive tests, such as a home-based fecal occult blood tests. Although these screening methods prove helpful, they each have shortcomings.

In a study published in Gut, investigators sought to examine the use of gut microbes as indicators of the disease.

“A number of studies have shown an association between fecal microbes and colorectal cancer; however, there is limited agreement in the types of microbes reported,” said first author Dr Manasi Shah. “I was interested in finding a microbial marker for the disease. One way to do this is by carrying out a single-institution study, but this takes a long time for sample collection, involves sequencing the microbes’ DNA, and is expensive.”

Dr Shah noticed that some published research provided the means necessary for accessing the raw microbial DNA sequencing data of the samples.

“How great it would be, I thought, if I could leverage existing raw data across multiple cohorts and come up with a generalizable marker for the disease,” Dr Shah said.

She collaborated with senior author Dr Emily Hollister from the Texas Children’s Microbiome Center, to learn the necessary tools to reprocess microbial sequence data from its original form.

“Manasi had the interest, and we had the expertise,” Dr Hollister said. “In our center, we had been planning to compare a series of different statistical tools to analyze large amounts of microbiome data.”

The authors reanalyzed raw bacterial DNA sequence data from several studies. They confirmed previously reported types of bacteria associated with colorectal cancer, and identified other bacteria not previously associated with the cancer.

“In our experience, collecting the raw data from the published studies was an uphill task,” Dr Shah said. “Some studies shared all the sample-associated microbial DNA sequences and clinical data, others only shared partial data or did not share any data at all. After much effort, I was able to gather data from 9 of 12 published studies. This highlights the need for an initiative to encourage investigators to share their data upon publication, which will help wider dissemination and reproducibility in the field.”

An additional challenge in the study were the various technological approaches the different laboratories used to analyze the samples.

“This was an incredibly large, complex multinational study,” said co-author Todd DeSantis. “We saw many differences between medical centers in the way each collected and stored stool samples and in the methods used to process the bacterial DNA in stools. These differences can be problematic for identifying the bacterial strains that proliferate in cancer patients, but our Second Genome KnowledgeBase Team, led by co-author Thomas Weinmaier, found ways to enhance our software platform to address these differences along the way. The findings that emerged from this challenging data set helped validate our platform, and in the process we were able to deliver high-quality insights to advance our collaboration with Dr Hollister.”

The investigators used a variety of statistical tools to uniformly reanalyze large amounts of raw bacterial DNA sequence data from several studies. They confirmed the previously reported types of bacteria associate with the disease and the other bacteria that was not previously associated.

“The fact that even when we combined several different studies we could correctly classify a sample as a colorectal cancer case or control with 80% accuracy solely based on microbial abundances was very encouraging,” Dr Shah said.

Hollister added, “This is a promising first step to develop a noninvasive test that might be used in the detection of colorectal cancer, supplementing colonoscopy or fecal occult blood tests.”

The authors noted that their findings could be adapted to use with other diseases.

“The same strategy could be applied for developing diagnostic tests or therapeutics for other diseases such as inflammatory bowel disease, nonalcoholic steatohepatitis, type 2 diabetes, and Alzheimer’s disease, among others for which the microbiome is currently being investigated,” Dr Shah concluded.