Gut microbiome offers clues to disparities in rectal cancer
UT Southwestern study identifies clustering of specific gut bacteria associated with race, ethnicity in patients
DALLAS – March 25, 2024 – The composition of the gut microbiomes in a group of rectal cancer patients reveals distinct signatures by race, ethnicity, and age of onset, with white Hispanics showing significant presence of one specific type of bacteria, UT Southwestern Medical Center researchers report. Published in the Journal of Immunotherapy and Precision Oncology, the study provides insights that could benefit future prevention efforts or therapies for rectal and colorectal cancer that involve manipulating the microbiome.
“Our study used serial statistical methods to look at the makeup of the gut microbiome in diverse groups of patients undergoing treatment for rectal cancer, and the result suggests that the particular microbial taxa Prevotellaceae may be involved in the pathogenesis of the disease,” said Nina Sanford, M.D., Assistant Professor of Radiation Oncology and Chief of Gastrointestinal Radiation Oncology Service at UT Southwestern. Dr. Sanford co-led the study with Andrew Koh, M.D., Associate Professor of Pediatrics in the Division of Pediatric Hematology and Oncology and of Microbiology. Both are members of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.
The increasing number of early-onset colorectal cancer (EOCRC) diagnoses among patients younger than age 50 has raised concerns in recent decades. About 20% of all colorectal cancer cases are now in people younger than 55, according to the American Cancer Society. Hispanic populations have been found to have a higher risk of early-age diagnosis. However, the genetic characteristics of their EOCRC tumors did not differ from those developed at a more typical age, prompting researchers to look into other factors.
In this study, UTSW researchers examined the composition and abundance of the gut microbiome in groups categorized by race, ethnicity, and age of onset to understand the potential links between microbiome signatures and diseases and treatment outcomes.
Among 64 rectal cancer patients being treated at Parkland Health and UTSW between October 2020 and August 2022, half were younger than 51, and 30 patients were Hispanic. Stool samples collected from patients were sequenced to identify microorganisms. The researchers then compared the identified microbiome across demographics such as age and race. They used multiple statistical methods to improve comparison reliability rather than the widely used single statistical method.
UTSW researchers found that white Hispanic populations had a significant enrichment of Prevotellaceae, a bacterial family known for both improved glucose metabolism as well as higher rates of inflammatory disease and chemotherapy-induced toxicity. Among Hispanics, Prevotellaceae has also been linked with higher obesity, a potential risk factor for colorectal cancers.
When comparing ages, the researchers found no common microorganisms among younger or older patients. However, younger patients had less diversity in gut microbiome compositions, which was generally linked with poorer health outcomes, the study showed.
The next step may involve experiments to assess the effect of Prevotellaceae on cancer progression. “If we identify a distinctive signature in human populations, it would be useful to investigate whether this specific microorganism directly causes the disease or changes the response to treatment,” Dr. Koh said.
Potential therapeutic strategies for preventing or treating EOCRC in the future could include microbiome manipulation, such as dietary modifications, selective antibiotics, precision probiotics, and fecal microbiota transplant, according to the authors.
“Our study will spark the conversation about urging further exploration into the microbiome’s role in rectal cancer and its broader implications for colorectal health,” said Dr. Sanford, a Dedman Family Scholar in Clinical Care.
Other UTSW researchers who contributed to the study are David Hein, M.S., Data Scientist with the Lyda Hill Department of Bioinformatics; and Laura Coughlin, M.A., Senior Research Associate/Lab Manager, and Nicole Poulides, M.S., Research Assistant, both in the Koh Lab.
This study is supported by grants from the National Institutes of Health (K24 AI123163), the UT Southwestern and Children’s Health Pediatric Cellular and ImmunoTherapeutics Program, the Harold C. Simmons Comprehensive Cancer Center Early Onset Colorectal Cancer Pilot Funding Program, and the National Cancer Institute Cancer Center Support Grant (P30CA142543).
More information on this research, including the authors’ financial disclosures, can be found in the study.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.
About Parkland Health
Parkland Health is one of the largest public hospital systems in the country. Premier services at the state-of-the-art Parkland Memorial Hospital include the Level I Rees-Jones Trauma Center, the only burn center in North Texas verified by the American Burn Association for adult and pediatric patients, and a Level III Neonatal Intensive Care Unit. The system also includes two on-campus outpatient clinics – the Ron J. Anderson, MD Clinic and the Moody Outpatient Center, as well as more than 30 community-based clinics and numerous outreach and education programs. By cultivating its diversity, inclusion, and health equity efforts, Parkland enriches the health and wellness of the communities it serves. For more information, visit parklandhealth.org.