Targeting Bile-Acid Metabolism: Nutritional and Microbial Approaches to Alleviate Ulcerative Colitis
Abstract
:1. Introduction
2. The Current Status of UC
3. Bile-Acid Metabolism
3.1. Classification and Synthesis of BAs
3.2. Mutual Regulation of Microbiota and BAs
3.3. Receptors Involved in BA Metabolism
3.3.1. FXR
3.3.2. VDR, PXR, and CAR
3.3.3. TGR5
3.3.4. M3R and S1PR2
4. UC and BA Metabolism
4.1. Disrupted BA Metabolism and Intestinal Flora Drive UC
4.2. Regulation of UC by BA Receptors
4.2.1. FXR Regulates the Immune Response and Intestinal Health
4.2.2. TGR5 Bridges Inflammation and Immune Responses
5. BA-Based Therapies
5.1. Dietary and Phytochemical Strategies
5.2. Fecal Microbial Transplantation (FMT) and Probiotic Measurements
6. Summary and Perspective
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
UC | Ulcerative colitis |
IBD | Inflammatory bowel disease |
BAs | Bile acids |
FXR | Farnesoid X receptor |
TGR5 | Takeda G protein-coupled receptor 5 |
DALYs | Disability-adjusted life years |
SCFAs | Short-chain fatty acids |
CRC | Colorectal cancer |
CA | Cholic acid |
CDCA | Chenodeoxycholic acid |
DCA | Deoxycholic acid |
LCA | Lithocholic acid |
UDCA | Ursodeoxycholic acid |
α/β-MCA | α/β-muricholic acid |
BSEP | Bile salt export pump |
BSH | Bile salt hydrolase |
OATPs | Organic Anion Transport Proteins |
ASBT | Apical sodium-dependent bile-acid transporter |
VDR | Vitamin D receptor |
PXR | Pregnane X receptor |
CAR | Constitutive androstane receptor |
M3R | Muscarinic acetylcholine receptor M3 |
S1PR2 | Sphingosine-1-phosphate receptor 2 |
FGF15/19 | Fibroblast growth factor 15/19 |
AOM | Azoxymethane |
BAD | Bile-acid-induced diarrhea. |
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Study Design | Reference | Main Findings |
---|---|---|
Mouse colon and enterocyte-like cells treated with medium or INT-747. | Gadaleta et al., 2011 [79] | FXR activation inhibits the secretion of TNF-α in immune cells (such as PBMCs and CD14+ monocytes). |
Fxr−/− and WT mice treated with GW4064 or vehicle for 2 days and then subjected to BDL or sham operation. | Inagaki et al., 2006 [84] | FXR activation increases genes involved in enterοprotection and decreases bacterial overgrowth and mucosal injury in the ileum. |
Rats subjected to BDL or not, and treated with vehicle 5 mg/kg GW4064 or UDCA. | Verbeke et al., 2015 [85] | FXR activation normalizes ileal permeability and reduces bacterial translocation, resulting in a significant decrease in natural killer cells and INF-γ expression. |
Patients with BAD (n = 28) received oral INT-747 acid 25 mg daily for 2 weeks. | Walters et al., 2015 [87] | FXR activation induced by INT-747 reduces hepatic BA synthesis and improves diarrhea symptoms. |
IHC was used to detect FXR in tissues from healthy human samples (n = 238), polyps (n = 32), and adenocarcinomas stages I-IV (n = 43, 39, 68, and 9, respectively). | Bailey et al., 2014 [89] | FXR expression decreases in samples from patients with precancerous lesions and is nearly absent in advanced colon adenocarcinoma samples. |
Fxr−/− and WT mice intraperitoneally injected with sterile saline with or without AOM once a week for 6 weeks. | Maran et al., 2009 [90] | FXR deficiency promotes cell proliferation, inflammation, and tumorigenesis in the intestine, suggesting that FXR may protect against intestinal carcinogenesis. |
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Jiang, X.; Ren, J.; Yu, G.; Wu, W.; Chen, M.; Zhao, Y.; He, C. Targeting Bile-Acid Metabolism: Nutritional and Microbial Approaches to Alleviate Ulcerative Colitis. Nutrients 2025, 17, 1174. https://doi.org/10.3390/nu17071174
Jiang X, Ren J, Yu G, Wu W, Chen M, Zhao Y, He C. Targeting Bile-Acid Metabolism: Nutritional and Microbial Approaches to Alleviate Ulcerative Colitis. Nutrients. 2025; 17(7):1174. https://doi.org/10.3390/nu17071174
Chicago/Turabian StyleJiang, Xiaoxin, Jingyi Ren, Gejun Yu, Wentao Wu, Mengyuan Chen, Yun Zhao, and Canxia He. 2025. "Targeting Bile-Acid Metabolism: Nutritional and Microbial Approaches to Alleviate Ulcerative Colitis" Nutrients 17, no. 7: 1174. https://doi.org/10.3390/nu17071174
APA StyleJiang, X., Ren, J., Yu, G., Wu, W., Chen, M., Zhao, Y., & He, C. (2025). Targeting Bile-Acid Metabolism: Nutritional and Microbial Approaches to Alleviate Ulcerative Colitis. Nutrients, 17(7), 1174. https://doi.org/10.3390/nu17071174