For most of us, ecology is external—something we simply admire on road trips and hiking expeditions. For Cancer Center at Illinois (CCIL) member Christopher Gaulke and his research team, however, the most fascinating kind of ecosystem resides inside of us, as we are each hosts to trillions of microorganisms living inside our body’s microbiome. Though the human body can house microbes in many locations, the gut microbiome is what interests Gaulke and his team, as it holds important implications for various diseases and gastrointestinal cancers.
“Going all the way back to undergrad, I started in ecology,” described Gaulke on his academic beginnings. “I was interested in frog fungus, Batrachochytrium dendrobatidis, which then got me interested in diseases in general. Then, during my Ph.D., I ended up being the point person for the lab’s microbiome analysis in SIV infection and HIV infection.”
Gaulke’s work with HIV-microbiome interactions sparked his interest in how the microbiome may be more broadly involved in promoting human health. Though he possessed the ecology, microbiology, and molecular training to conduct microbiome studies, he knew he lacked the deep knowledge of bioinformatics needed to truly dig into the mechanisms that underpin host-microbiome interactions. This spurred him to pursue a postdoc in microbiome analysis working with a bioinformatician and biostatistician, Thomas Sharpton, at Oregon State University where he could build this skill set.
However, Gaulke’s work didn’t end there.
“Now, we’re far more focused on two main things in my lab, the first being microbiome interactions with toxicants,” he explained. “The other involves understanding the role of the microbiome in carcinogenesis for gastrointestinal cancers, using both preclinical animal models and human clinical cohorts.”
A diagram from the Song Lab at Harvard T.H. Chan School of Public Health, displaying how several factors like diet, metabolism, and microbiome composition affect one another and an individual’s risk for cancer.
The gut microbiome has two key ways of providing insight into gastrointestinal cancers: one through acting as a predictive screening tool, and another as a potential therapy agent for those at higher risk of developing these kinds of cancers. Regarding the former, Gaulke developed a collaboration with Oregon Health and Science University (OHSU) to compare the microbiota of patients with pre-cancerous polyps and those without.
“In this study, we wanted to determine if changes in the microbiome observed late in colorectal cancer progression were also present in its earliest, precancerous stages. What we found was pretty surprising. Patients that presented with colonic adenomas—a benign tumor that, if untreated, can develop into cancer—had highly distinct microbial signatures from non-adenoma formers. In fact, some of the same taxa that are altered in later stages of colorectal cancer were disrupted early in the tissue.” Gaulke goes on to further describe the implications of these findings. “This told us that early changes in the microbiome during colorectal cancer may begin at tissue surfaces, which means these screening biopsies could potentially be used as biomarkers.”
Though there are drawbacks to this form of modeling—including the invasive use of an endoscopy to collect tissues from the gut—the ability to accurately predict polyp formation before cancer even develops could be a game-changer in stopping the deadly disease in its tracks.
In addition to its use as a predictive tool, Gaulke and his collaborators at OHSU are investigating potential therapeutic measures for those with microbial indicators of disease. Diet is one of the primary determinants of what composes the gut microbiome, as well as a great risk factor for colorectal cancer. According to Gaulke, those with microbiomes associated with polyp formation tended to eat lower levels of fruits, grains, and vegetables. In addition, those individuals also had microbiomes with a lower abundance of genes that create beneficial short chain fatty acids, which are derived from the food groups above, as well as others high in soluble fiber content.
“Now, we have a cohort where we’re trying to determine whether or not we can shift a microbiome, just by using fiber, to make it more consistent with what we saw in our healthy cohort,” Gaulke described. “If that’s the case, then we can potentially give this fiber to those with precancerous adenomas to reduce their risk of continuing on to colorectal cancer.”
Gaulke and his collaborators at OHSU are currently analyzing how the microbiome and its metabolism can be altered by therapeutics like this fiber, in the hopes that it can shift those at higher risk of colorectal cancer to a healthier microbiome, hoping to prune and protect the forests that live inside of us.
Editor’s notes:
Christopher Gaulke is an Assistant Professor in Pathobiology at the University of Illinois Urbana-Champaign School of Veterinary Medicine. He is also an Affiliate with the Personalized Nutrition Initiative at the Carle R. Woese Institute for Genomic Biology, as well as the National Center for Supercomputing Applications (NCSA). He can be reached at cgaulke@illinois.edu.
This story was written by Chloe Zant, CCIL Communications intern.