Bile acids (BAs) affect the intestinal environment by ensuring barrier integrity, maintaining microbiota balance, regulating epithelium turnover, and modulating the immune system. As a master regulator of BA homeostasis, farnesoid X receptor (FXR) is severely compromised in patients with inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). At the front line, gut macrophages react to the microbiota and metabolites that breach the epithelium. We aim to study the role of the BA/FXR axis in macrophages. This study demonstrates that inflammation-induced epithelial abnormalities compromised FXR signaling and altered BAs’ profile in a mouse CAC model. Further, gut macrophage–intrinsic FXR sensed aberrant BAs, leading to pro-inflammatory cytokines’ secretion, which promoted intestinal stem cell proliferation. Mechanistically, activation of FXR ameliorated intestinal inflammation and inhibited colitis-associated tumor growth, by regulating gut macrophages’ recruitment, polarization, and crosstalk with Th17 cells. However, deletion of FXR in bone marrow or gut macrophages escalated the intestinal inflammation. In summary, our study reveals a distinctive regulatory role of FXR in gut macrophages, suggesting its potential as a therapeutic target for addressing IBD and CAC.
Xingchen Dong, Ming Qi, Chunmiao Cai, Yu Zhu, Yuwenbin Li, Sally Coulter, Fei Sun, Christopher Liddle, Nataliya V. Uboha, Richard Halberg, Wei Xu, Paul Marker, Ting Fu
Usage data is cumulative from January 2024 through May 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 1,751 | 305 |
329 | 60 | |
Figure | 366 | 8 |
Supplemental data | 84 | 4 |
Citation downloads | 30 | 0 |
Totals | 2,560 | 377 |
Total Views | 2,937 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.