Sun developing new strategy to prevent, treat colon cancer

University of Illinois at Chicago researcher Jun Sun is developing a new strategy to restore host-microbe relationships that can potentially prevent and treat colon cancer.

The gut microbiome, a newly discovered “organ” that aids in the body’s digestion of food, metabolism, immune function and brain health, plays a critical role in the maturation and continued education of the host immune response, said Sun, PhD, AGAF, FAPS, professor of gastroenterology and hepatology at the University of Illinois College of Medicine.

Gut microbiome also provides protection against pathogen overgrowth; influences host-cell proliferation; regulates intestinal endocrine functions, neurologic signaling, and bone density; provides a source of energy for biogenesis (5% to 10% of daily host energy requirements); biosynthesizes vitamins, neurotransmitters, and modulates drug metabolism; and eliminates toxins growing outside an organism. 

“The number of gut microbiota genes exceeds the number of genes in the human genome by 150 times,” said Sun, who is also a member of the University of Illinois Cancer Center’s Cancer Biology Program. “Thus, it is not surprising that the disruption of the gut’s symbiotic ecological communities has been consistently linked to various gastrointestinal pathologies, including in colorectal cancer.”

Sun’s latest work has been published and featured in the journal Cellular and Molecular Gastroenterology and Hepatology.

Sun’s laboratory is studying how vitamin D and vitamin D receptor (VDR) could benefit the intestinal microbiome. Vitamin D deficiency and a weakened or disrupted VDR – a regulator of hundreds of down-stream genes – have been related in the pathology of at least 17 types of cancer, including colon cancer. However, it is unknown how intestinal epithelial vitamin D receptor is involved in maintaining intestinal and microbial homeostasis.

“Our long-term goal is to address this issue, while providing a novel approach that can potentially prevent and treat colon cancer by restoring host-microbe relationships,” she said.

Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in both men and women in the United States, according to the American Cancer Society, which estimates that 104,610 new cases of colon cancer will be reported in 2020, with 43,340 new cases of rectal cancer being diagnosed this year. Colorectal cancer is the third leading cause of cancer-related deaths in men and women in the U.S., and the second most common cause of cancer deaths when men and women are combined. It’s expected to cause about 53,200 deaths in 2020, according to the ACS.

Sun and her colleagues are pioneers in the study of microbiome altered by the expression of vitamin D receptor in the intestine. In another collaborative study published in the journal Nature Genetics, Sun demonstrated that human VDR is a key host factor in shaping gut microbiome. She also observed significant shifts in the VDR’s microbiota in mice and correlations between the microbiota and serum measurements of select human bile and fatty acids, and has reported dysbiosis – an action that typically occurs when the bacteria in the gastrointestinal tract becomes unbalanced – that has an increased abundance of Bacteroidaceae and decreased genus Lactobacillus and butyrate-producing bacteria in the intestine lacking VDR.

“Our studies have also demonstrated that vitamin D receptor protects the host from invasive pathogens, maintains intestinal homeostasis, and reduces risk of colorectal cancer,” Sun said. “Our data fill these knowledge gaps by elucidating the mechanisms of VDR in preventing microbiome-mediated cancer.”

Vitamin D deficiency is most prevalent in minorities. Studies to test vitamin D and VDR as a causal factor is of major public health significance, and understanding VDR in colorectal cancer will “help us to understand the disparities in colorectal cancer and serve the mission of the University of Illinois Cancer Center. Our research will not only advance the understanding of how VDR and microbiome is involved in the pathogenesis of colon cancer, but it will offer an additional avenue to treat colon cancer by restoring the function of VDR and microbiome, allowing us to develop a new protocol for risk assessment and prevention of cancer,” Sun said.

Sun is currently chairing the microbiome and microbial therapy section of the American Gastroenterological Association (AGA), an international society with more than 16,000 members. She is actively involved in advocating microbiome research at the international, national and institutional levels.

Sun’s research is funded by the UI Cancer Center, the National Institute of Diabetes and Digestive and Kidney Diseases grant number R01DK015118, R01DK114126, and U.S. Department of Defense grant number BC160450P1.

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