Abstract
Gastrointestinal (GI) homeostasis is strongly dependent on nuclear receptor (NR) functions. They play a variety of roles ranging from nutrient uptake, sensing of microbial metabolites, regulation of epithelial intestinal cell integrity to shaping of the intestinal immune cell repertoire. Several NRs are associated with GI pathologies; therefore, systematic analysis of NR biology, the underlying molecular mechanisms, and regulation of target genes can be expected to help greatly in uncovering the course of GI diseases. Recently, an increasing number of NRs has been validated as potential drug targets for therapeutic intervention in patients with inflammatory bowel disease (IBD). Besides the classical glucocorticoids, especially PPARγ, VDR, or PXR-selective ligands are currently being tested with promising results in clinical IBD trials. Also, several pre-clinical animal studies are being performed with NRs. This review focuses on the complex biology of NRs and their context-dependent anti- or pro-inflammatory activities in the regulation of gastrointestinal barrier with special attention to NRs already pharmacologically targeted in clinic and pre-clinical IBD treatment regimens.
Highlights
This review is based on the most recent advances in our understanding of the complex biology of nuclear receptors (NRs) within both the healthy and inflamed intestinal tract (Tables 1–3) and the emerging number of ligands successfully used in preclinical and clinical trials (Table 4) to target inflammation and treat inflammatory bowel disease (IBD) without focusing on intestinal infections [1,2,3,4,5]
This review focuses on the complex relationship between nutrition, inflammation and nuclear receptor biology within the GI and the emerging number of NR ligands used in IBD therapy
NRs and NR ligands control important gastrointestinal functions ranging from nutrient uptake, the composition of the microbiota and intestinal immune cells
Summary
This review is based on the most recent advances in our understanding of the complex biology of nuclear receptors (NRs) within both the healthy and inflamed intestinal tract (Tables 1–3) and the emerging number of ligands successfully used in preclinical and clinical trials (Table 4) to target inflammation and treat inflammatory bowel disease (IBD) without focusing on intestinal infections [1,2,3,4,5]. Several members of the NR family have a protective role during disease progression, and their loss in different IBD animal models (DSS, TNBS, T cell transfer, or infection) leads to exacerbated colitis symptoms (Tables 1–3) (Figure 1).
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