What does your gut say about caffeine?
Inside every person’s digestive system are trillions of microorganisms that affect health. Gut microbes extract nutrients and digest fibre from the food we eat, shape our immune system and do their part to protect us from pathogens. However, not all microbes are beneficial. Some are associated with the development of disease, but exactly why and how remains a mystery. Seeking to shed light on the matter, scientists supported by the EU-funded IMMUNOBIOME and SYSCID projects investigated what leads to the generation of an important subtype of cells in the intestine known as Interleukin-17-producing T helper (Th17) cells. They discovered some less recognised molecular players and their role in cell differentiation in the gut. One such player is the purine metabolite xanthine, usually found in caffeinated foods such as tea leaves and coffee and cacao beans. The study was published in the journal ‘Immunity’. “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,” remarks co-lead author Dr Jinzhi Duan of Harvard Medical School in an article posted in ‘The Harvard Gazette’. Th17 cells are believed to play an important role in the intestine, helping to defend it against bacterial and fungal pathogens. However, they have also been implicated in the development of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease (IBD). “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,” states Dr Duan.
An unexpected discovery
The researchers’ investigation into the steps resulting in Th17 cell differentiation led to the discovery of xanthine’s role in the intestine. “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,” explains co-senior author Prof. Richard Blumberg, also of Harvard Medical School. “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.” Studying the development of Th17 cells in mouse models, the team found that Th17 cells were able to proliferate in germ-free mice as well as in mice that had been administered bacteria-eliminating antibiotics. Endoplasmic reticulum stress in intestinal epithelial cells drove gut Th17 cell differentiation through purine metabolites such as xanthine. Further research is required to find what causes Th17 cells to play a role in disease development. “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,” notes Prof. Blumberg. The IMMUNOBIOME (Identifying microbiotal triggers of inflammatory bowel disease through the lens of the immune system) project ended in 2020. SYSCID (A Systems medicine approach to chronic inflammatory disease) ended in 2022. For more information, please see: SYSCID project website
Keywords
IMMUNOBIOME, SYSCID, caffeine, intestine, gut, microbe, Th17, cell differentiation, disease, immune system
