A new compound that reverses gut inflammation in mice

Good news! This could potentially be breakthrough! Almost like a wonder drug! Best of all, this drug is well known already!

"A drug developed by ... researchers acts like a master reset switch in the intestines. The compound, called FexD, has previously been found to lower cholesterol, burn fat, and ward off colorectal cancer in mice. Now, the team reports ... that FexD can also prevent and reverse intestinal inflammation in mouse models of inflammatory bowel disease. ...
"... provides a new way to restore balance to the digestive system and treat inflammatory diseases that are currently very difficult to manage,” ...
For more than two decades, ... lab has studied Farnesoid X receptor (FXR), a master regulator protein that senses the bile acids delivered to the digestive system to help digest food and absorb nutrients. When FXR detects a shift in bile acids at the beginning of a meal, it prepares the body for an influx of food by flipping on and off dozens of cellular programs related to digestion, blood sugar, and fat metabolism. ...
In the new work, ... discovered that activating FXR can be used to ease symptoms in inflammation-driven diseases. When the researchers gave mice with IBD a daily dose of oral FexD, either before or after the onset of intestinal inflammation, the drug prevented or treated the inflammation. By activating FXR, FexD reduced the infiltration of a class of highly inflammatory immune cells called innate lymphoid cells. In turn, levels of cytokines already implicated in IBD decreased to levels normally seen in healthy mice. ..."

From the significance and abstract:

"Significance

In addition to promoting lipid and fat-soluble vitamin absorption, bile acids (BAs) function as signaling molecules that coordinate persistent changes in intestinal cells. As such, BA homeostasis is tightly regulated by the Farnesoid X Receptor (FXR). This study elucidates a previously unknown role for FXR in regulating innate lymphoid cells (ILCs), wherein activation of FXR abrogates ILC3-dependent intestinal inflammation. Establishing FXR as an intrinsic regulator of ILCs provides a functional connection between diet and innate immunity. Moreover, with synergistic effects in both intestinal epithelial and immune cells, these findings implicate FXR agonism as an integrative therapeutic strategy for chronic intestinal inflammation.

Abstract

The pleiotropic actions of the Farnesoid X Receptor (FXR) are required for gut health, and reciprocally, reduced intestinal FXR signaling is seen in inflammatory bowel diseases (IBDs). Here, we show that activation of FXR selectively in the intestine is protective in inflammation-driven models of IBD. Prophylactic activation of FXR restored homeostatic levels of pro-inflammatory cytokines, most notably IL17. Importantly, these changes were attributed to FXR regulation of innate lymphoid cells (ILCs), with both the inflammation-driven increases in ILCs, and ILC3s in particular, and the induction of Il17a and Il17f  in ILC3s blocked by FXR activation. Moreover, a population of ILC precursor-like cells increased with treatment, implicating FXR in the maturation/differentiation of ILC precursors. These findings identify FXR as an intrinsic regulator of intestinal ILCs and a potential therapeutic target in inflammatory intestinal diseases."

Salk scientists develop compound that reverses gut inflammation in mice - Salk Institute for Biological Studies By targeting a molecule that keeps order in the gut, the new therapeutic has the potential to treat inflammatory bowel disease

FXR mediates ILC-intrinsic responses to intestinal inflammation (no public access)

[R]esearchers discovered the compound FexD can treat intestinal inflammation in mice. Mice with symptoms similar to inflammatory bowel disease had changes to the cells lining their intestines (left) that were reversed with treatment (right).