Xanthine in Coffee May Play Important Role in Gut Health

Researchers at Brigham and Women’s Hospital studying how and why certain cell types, namely Th17 cells proliferate in the gut, found that xanthine, found in coffee, tea, and chocolate may play an important role in gut health.

The study, newly published in Immunity, started by looking at some of the lesser-known molecular elements and processes that contribute to Th17 cell differentiation. Surprisingly, researchers stumbled upon a finding related to xanthine, a purine metabolite that is abundant in caffeine-containing foods.          

In a statement, the study’s co-lead author Jinzhi Duan, PhD explained that one of the concepts in gastroenterology is that microbes are required for Th17 cell differentiation, but this study’s findings showed that there may be exceptions. “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.”

They discovered that xanthine may play a role in gut health and refocused the study as such.

“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,” said senior author Richard Blumberg, MD. “It’s too soon to speculate on whether the amount of xanthine in a cup of coffee leads to helpful or harmful effects in a person’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.”

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Th17 cells, a type of T helper cell that produces interleukin-17, are believed to have significant implications in the gut. These cells can aid in constructing a defensive barrier in the intestinal tract, and when infections caused by bacteria or fungi occur, they may emit signals that lead to the production of more Th17 cells in the body. However, these cells have also been associated with various illnesses, including multiple sclerosis, rheumatoid arthritis, psoriasis, and IBD.

The researchers used mouse models to study Th17 cell development and were surprised to find that the cells could proliferate in germ-free mice or those given antibiotics. They discovered that Th17 cell differentiation was driven by endoplasmic reticulum stress in intestinal epithelial cells through purine metabolites, including xanthine. This process occurred even in mice lacking microorganisms and with genetic markers for protective cells.

The researchers acknowledge that their study only examined cells within the intestine and that intercellular communication between gut cells and organs such as the skin and lungs may have a significant impact on outcomes. They also state that their investigation did not reveal what triggers Th17 cells to become pathogenic and that further research, particularly studies focusing on human-IBD Th17 cells, is necessary.

Said Blumberg, “while we don’t yet know what’s causing pathogenesis, the tools we have developed here may take us a step closer to understanding what causes disease and what could help resolve or prevent it.”