Gut microbiota-mediated secondary bile acids regulate dendritic cells to attenuate autoimmune uveitis through TGR5 signaling

Hu, Jianping; Wang, Chaokui; Huang, Xinyue; Yi, Shenglan; S, Pan; Zhang, Yiting; Yuan, Guangjie; Cao, Qingfeng; Ye, Xingsheng; Li, Hong

doi:10.1016/j.celrep.2021.109726

Cited by 95 publications

(82 citation statements)

References 61 publications

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“…A robust model of human uveitis is experimental autoimmune uveitis (EAU), which can be induced by immunization with interphotoreceptor retinoid-binding protein (IRBP) [ 3 ]. Although immunosuppressive treatments including corticosteroids, antimetabolites, and alkylating agents are effective therapies, the nonspecific nature and the side effects preclude their long-term application [ 4 ]. Thus, searching more effective and less side-action therapeutic potential treatments is urgent.…”

Section: Introductionmentioning

confidence: 99%

Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1/M2 phenotypic polarization

Wang

et al. 2022

Redox Biology

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Section: Introductionmentioning

confidence: 99%

Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1/M2 phenotypic polarization

Wang

et al. 2022

Redox Biology

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“…TGR5 activation was further shown to downregulate cytokine production by inhibiting the NF-κB pathway in several cell types (Fig. 4 ), among which dendritic cells [ 148 ], NTK cells [ 131 ], endothelial cells [ 149 ], and macrophages and Kupffer cells [ 150 – 155 ]. In macrophages, NF-κB was inhibited by TGR5-dependent increased c-Fos phosphorylation [ 150 ], or by repressed phosphorylation of IκBα [ 151 , 152 ].…”

Section: Bile Acid Receptors and Inflammation In Cholestatic And Auto...mentioning

confidence: 99%

Bile acids and their receptors: modulators and therapeutic targets in liver inflammation

2022

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Bile acids participate in the intestinal emulsion, digestion, and absorption of lipids and fat-soluble vitamins. When present in high concentrations, as in cholestatic liver diseases, bile acids can damage cells and cause inflammation. After the discovery of bile acids receptors about two decades ago, bile acids are considered signaling molecules. Besides regulating bile acid, xenobiotic, and nutrient metabolism, bile acids and their receptors have shown immunomodulatory properties and have been proposed as therapeutic targets for inflammatory diseases of the liver. This review focuses on bile acid–related signaling pathways that affect inflammation in the liver and provides an overview of the preclinical and clinical applications of modulators of these pathways for the treatment of cholestatic and autoimmune liver diseases.

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“…Total genomic DNA from samples was extracted using the CTAB/ SDS method (Hu et al, 2021). DNA concentration and purity were monitored on 1% agarose gels.…”

Section: Sequencingmentioning

confidence: 99%

Integrated Analyses of Gut Microbiome and Host Metabolome in Children With Henoch-Schönlein Purpura

Wen

Dang

Feng

et al. 2022

Front. Cell. Infect. Microbiol.

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Recent studies have shown that intestinal microbes and metabolites are involved in the pathogenesis of many diseases. However, whether and how they are related to Henoch–Schönlein purpura (HSP) has yet to be understood. This work is designed to detect gut microbes, intestinal and serum metabolites in children with HSP, trying to discover the etiology and pathogenesis of HSP. A total of 86 children were recruited in this study, namely, 58 children with HSP (HSP group) and 28 healthy children as control groups (CON group). 16S rDNA amplicon sequencing technology and UPLC-QTOF/MS non-targeted metabolomics analysis were used to detect the intestinal microbes and metabolites, and also multi-reaction monitoring technology for detecting serum arachidonic acid (AA) and its metabolites. Then, correlation analysis was performed to explore the possible interaction between the differential gut microbes and metabolites. As a result, at the microbiota family level, the CON group had an advantage of Coriobacteriaceae while the HSP group had a dominant Bacteroidaceae. Five kinds of bacteria in the HSP group were significantly enriched at the genus level, and seven kinds of bacteria were significantly enriched in the CON group. A total of 59 kinds of gut metabolites significantly differ between the two groups, in which most are lipids and peptides. Spearman correlation analysis showed that Bacteroides, Dialister, and Agathobacter were associated with unsaturated fatty acids, especially AA metabolism. Then, we tested the AA related metabolites in serum and found thromboxane B2, leukotriene B4, prostaglandin D2, 9S-hydroxyoctadecadienoic acid, and 13S-hydroxyoctadecadienoic acid significantly changed. In conclusion, children with HSP had dominant Bacteroidaceae and decreased Coriobacteriaceae in the family level of gut microbes, and also lipids and peptides changed most in the gut metabolites. Our data suggested that the biosynthesis and metabolism of unsaturated fatty acids, especially AA and its metabolites, might participate in the occurrence and development of HSP.

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Gut microbiota-mediated secondary bile acids regulate dendritic cells to attenuate autoimmune uveitis through TGR5 signaling

Abstract: Highlights d Secondary bile acids reduce severity of experimental autoimmine uveitis (EAU) in mice d Altered bile acids are correlated with gut microbiota composition in EAU mice d Deoxycholic acid regulates the function of DCs via the TGR5-cAMP-PKA pathway

Cited by 95 publications

References 61 publications

Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1/M2 phenotypic polarization

Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1/M2 phenotypic polarization

Bile acids and their receptors: modulators and therapeutic targets in liver inflammation

Integrated Analyses of Gut Microbiome and Host Metabolome in Children With Henoch-Schönlein Purpura

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