Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease

Table 2 Potential applications of bile acids and their receptors in inflammatory bowel disease

Types	Ref.	Subjects	Treatment	Major findings
Bile acid receptor agonists or inhibitors	Miyazaki et al[109], 2021	Mice with AOM/DSS-induced colitis	Fed nelumal A for 15 wk	Nelumal A induced the expression of FXR target genes and tight junction proteins in the intestine; Nelumal A decreased the expression of hepatic bile acid synthesis genes
	Liu et al[110], 2023	Mice with DSS-induced colitis	Fed nigakinone for 9 d	Nigakinone inhibited inflammatory cytokine production by activating the FXR/NLRP3 signaling pathway; Nigakinone regulated bile acid metabolism by controlling cholesterol hydroxylase and FXR-mediated transporter proteins
	Qi et al[112], 2022	Mice with DSS-induced colitis	DDC gavage treatment for a week	DDC targeted and inhibited RORγt activity, thereby indirectly stabilizing Foxp 3 expression and achieving regulation of Th17/Treg homeostasis
	Chen et al[113], 2022	Mice with DSS-induced colitis	Fed compound 14d for 9 d	Compound 14d reduced RORγt-driven Th17 cell differentiation; Compound 14d attenuated T cell expansion and activation
	Chen et al[115], 2019	Mice with DSS-induced colitis	Fed genistein 14d for 9 d	Genistein lowered inflammatory cell infiltration and generation of pro-inflammatory mediators in the blood and colon; Genistein reduced weight loss and increased colon length in mice
	Han et al[118], 2022	Mice with DSS-induced colitis	Fed racemic compound 15 for 9 d	Racemic compound 15 showed good intestinal distribution and efficacy; Racemic compound 15 avoided unwanted systemic effects and showed better gallbladder safety
	Chen et al[119], 2018	Diet-induced obese mice	Fed compound 12 for 4, 8, 12, or 16 h	Compound 12 elicited a potent response with minimal effects on the gallbladder; Compound 12 stimulated prolonged and potent tGLP-1 secretion
	Dvořák et al[120], 2020	Mice with DSS-induced colitis	FKK6 oral gavage plus FKK6 intrarectal bolus for 10 d	FKK6 dramatically suppressed the production of pro-inflammatory cytokines and prevented inflammation; FKK6 provided the first evidence that microbial metabolite mimicry is a viable drug discovery strategy
Traditional Chinese medicine	Hua et al[122], 2021	Mice with DSS-induced colitis	Administrated with BTWT for 7 d	BTWT normalized the levels of some bile acids, especially CA and MCA; BTWT increased the expression of FXR and TGR5 in the liver; Relative species abundance and gut microbiota diversity were significantly higher in the BTWT-exposed group; BTWT significantly ameliorated colonic inflammation and clinical signs
	Su et al[123], 2022	Caco-2 cells treated with bile acids	Pre-incubated with GXD at subtoxic concentration for 24 h before treatment with BAs	GXD improved intestinal barrier dysfunction caused by abnormal bile acid metabolism in IBD by regulating tight junction protein expression levels, inhibiting oxidative stress, and reducing apoptosis
	Li et al[125], 2022	Mice with DSS-induced colitis	Fed SFE for 11 d	SFE regulated the transcriptional levels of RORγt and Foxp 3 in the colon and down-regulating the expression of the pro-inflammatory factor IL-17 A in colon tissue
	Shi et al[126], 2022	Mice with DSS-induced colitis	Fed LWE for a week	LWE inhibited the transcriptional activation of RORγT and IL-17A, thereby suppressing the differentiation of Th17 lymphocytes; LWE reduced inflammation and increased the protective action of the intestinal mucosal barrier via the TLR4/MyD88/NF-κB signal transduction pathway
	Xia et al[127], 2022	Mice with DSS-induced colitis	QCWZD gavage for a week	QCWZD inhibited the phosphorylation of JAK2-STAT3 pathway, reducing the transcriptional activation of RORγT and IL-17A
	Xiong et al[128], 2022	Mice with DSS-induced colitis	Fed HGT for 10 d	HGT inhibited DSS-induced necrotizing lesions in the colon through up-regulation VDR levels
	Zhang et al[129], 2020	Mice with DSS-induced colitis	PA administered intragastrically for 10 d	PA activated PXR signaling and inhibited NF-κB signaling, thereby ameliorating inflammation
	Yu et al[130], 2020	Mice with DSS-induced colitis	Fed Alpinetin for 9 d	Alpinetin activated PXR/NF-kB, thereby ameliorating inflammation

IBD: Inflammatory bowel disease; FXR: Farnesoid X receptor; PXR: Pregnane X receptor; VDR: Vitamin D receptor; RORγt: Retinoid-related orphan receptor γt; DSS: Dextran sodium sulfate; HGT: Huanglian Ganjiang Tang; QCWZD: Chingchang Wenzhong Decoction; LWE: Licorice water extraction; SFE: Sophora flavescens Aiton total flavonoids extracts; BTWT: Baitouweng Tang; GXD: Gualou Xiebai Decoctio; MCA: Muricholic acid.