Study probes caffeine’s role in gut health, IBD mentions also chocolate

I have not  yet finished my morning coffee, when I discovered this article in my email! What's in a gut! Caution: This article maybe overpromising!

As a chocolate addict I guess I have to visit Trader Joe's again to get my next half kilogram Belgium chocolate bar for about $6. Pardon my shameless plug, blame my addiction!

"A new study by investigators from Brigham and Women’s Hospital explores exactly what leads to the generation of Th17 cells — an important subtype of cells in the intestine — and uncovers some of the underappreciated molecular players and events that lead to cell differentiation in the gut. One of those players is the purine metabolite xanthine, which is found at high levels in caffeinated foods such as coffee, tea and chocolate. ...
“While illuminating the steps leading to Th17 cell differentiation, the researchers unexpectedly discovered a role for xanthine in the gut.
... “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 ..."

From the highlights and abstract (I am not exactly sure how coffee relates to xanthine):

"Highlights

• ER stress in intestinal epithelial cells (IEC) drives gut Th17 differentiation

• Th17 cells induced by IEC-ER stress require H2O2 generated by DUOX2/DUOXA2

• IEC-ROS induce Th17 differentiation through purine metabolites, including xanthine

• IEC-ER stress drives microbial Th17 induction even under germ-free conditions

Summary

Intestinal IL-17-producing T helper (Th17) cells are dependent on adherent microbes in the gut for their development. However, how microbial adherence to intestinal epithelial cells (IECs) promotes Th17 cell differentiation remains enigmatic. Here, we found that Th17 cell-inducing gut bacteria generated an unfolded protein response (UPR) in IECs. Furthermore, subtilase cytotoxin expression or genetic removal of X-box binding protein 1 (Xbp1) in IECs caused a UPR and increased Th17 cells, even in antibiotic-treated or germ-free conditions. Mechanistically, UPR activation in IECs enhanced their production of both reactive oxygen species (ROS) and purine metabolites. Treating mice with N-acetyl-cysteine or allopurinol to reduce ROS production and xanthine, respectively, decreased Th17 cells that were associated with an elevated UPR. Th17-related genes also correlated with ER stress and the UPR in humans with inflammatory bowel disease. Overall, we identify a mechanism of intestinal Th17 cell differentiation that emerges from an IEC-associated UPR."

Study probes caffeine’s role in gut health, IBD – Harvard Gazette Researchers find new clues on causes of inflammatory bowel disease

Endoplasmic reticulum stress in the intestinal epithelium initiates purine metabolite synthesis and promotes Th17 cell differentiation in the gut (no public access)

Graphical abstract