Purine metabolite xanthine, found in caffeinated beverages and food, affect cell differentiation, and new study results may lead to more knowledge about why diseases such as IBD develop.
Purine metabolite xanthine, which is found in caffeinated foods, including chocolate, coffee, and tea, plays a role in cell differentiation in the gut microbiome, according to the results of a study published in Immunity.
Some microorganisms were thought to contribute to the development of inflammatory conditions, including inflammatory bowel disease (IBD). Investigators from Brigham and Women’s Hospital (BWH), part of Mass General Brigham health care system, examined what could lead to the generation of interleukin-17-producing T helper (Th17) cells, an important subtype of cells in the intestines.
“One of the concepts in our field is that microbes are required for Th17 cell differentiation, but our study suggests that there may be exceptions,” Jinzhi Duan, PhD, instructor in medicine in the Division of Gastroenterology, Hepatology, and Endoscopy in the Department of Medicine at BWH, said in a statement. “We studied the underlying mechanisms of Th17 cell generation in the gut and found some surprising results that may help us to better understand how and why diseases like IBD may develop.”
While looking at the steps leading to Th17 cell differentiation, which is thought to play a key role in the intestine by building a protective barrier in the gut, investigators discovered that xanthine plays a role.
In the study, investigators used several mouse models to study the molecular events that led to the development of Th17 cells. These cells may release signals to the body, which produce more Th17 cells when a bacterial or fungal infection occurs. However, the cells have also been implicated in IBD, multiple sclerosis, psoriasis, and rheumatoid arthritis.
Investigators found that Th17 cells could proliferate even in germ-free mice or mice that had been given antibiotics that wiped out bacteria. They also found that endoplasmic reticulum stress in intestinal epithelial cells drove Th17 cell differentiation through purine metabolites, such as xanthine, even in mice without the microbes and with genetic signatures that suggested cells with protective properties.
“Sometimes in research, we make these serendipitous discoveries; it’s not necessarily something you sought out, but it’s an interesting finding that opens up further areas of inquiry,” Richard Blumberg, MD, of the Division of Gastroenterology, Hepatology, and Endoscopy in the Department of Medicine, said in the statement. “It’s too soon to speculate on whether the amount of xanthine in a cup of coffee leads to helpful or harmful effects in [an individual’s] gut, but it gives us interesting leads to follow up on as we pursue ways to generate a protective response and stronger barrier in the intestine.”
Investigators noted that the limitation in their study included only cells in the intestines, so it could be possible that cells in the gut cross over with other organs.
Further exploration is needed, including studies focused on human IBD Th17 cells, they said.
This study does not indicate what causes Th17 cells to become pathogenic.
Molecular component of caffeine may play a role in gut health. News release. Brigham and Women’s Hospital. March 14, 2023. Accessed March 15, 2023. Email.