ALLERGY
·
2021
·Vol. 77
·期 2
·483-498
·
IF 13.146
Renlan Wu,Xiefang Yuan,Xingjie Li,Ning Ma,Hongyu Jiang,Hongmei Tang,Guofeng Xu,Zhigang Liu,Zongde Zhang
Background Alteration of commensal microbiota is highly correlated with the prevalence of allergic reactions to food in the gastrointestinal tract. The mechanisms by which microbiota modulate food allergen sensitization in the mucosal site are not fully understood. Methods We generate DCs specific knockout of retinoic acid receptor α (Rara) gene mice (DC KO Rara) to evaluate food sensitization. The bile acid-activated retinoic acid response was evaluated by flow cytometry, real-time RT-PCR and Illumina transcriptome sequencing. The global effect of Abx treatment on BA profiles in the mucosal lymph tissue mLN in mice was examined by UPLC-MS analysis. Results In this study, we demonstrate that depletion of commensal gut bacteria leads to enhanced retinoic acid (RA) signaling in mucosal dendritic cells (DCs). RA signaling in DCs is required for the production of food allergen-specific IgE and IgG1. Antibiotics induced an enlarged bile acid (BA) pool, and dysregulated BA profiles contributed to enhanced RA signaling in mucosal DCs. BA-activated RA signaling promoted DC upregulation of interferon I signature, RA signature, OX40L, and PDL2, which may lead to T helper 2 differentiation of CD4+ T cells. BA-activated RA signaling involved the farnesoid X receptor and RA receptor α (RARa) interaction. Depletion of bile acid reduces food allergen specific IgE and IgG1 levels in mice. Conclusion Our research unveils a mechanism of food sensitization modulated by BA-RA signaling in DCs, which suggests a potential new approach for the intervention of food allergic reactions.
研究领域:
免疫学
·
微生物学
·
过敏
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Clinical and Translational Hepatology
·
2023
·
IF 3.6
Fulin Nian,Longyun Wu,Qiaoyun Xia,Peiying Tian,Chunmei Ding,Xiaolan Lu
Background and aims Non-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota and has become the most common chronic liver disease worldwide, but the relationship between specific strains and NAFLD has not been fully elucidated. We aimed to investigate whether Akkermansia muciniphila and Bifidobacterium bifidum could prevent NAFLD, the effects of their action alone or in combination, possible mechanisms, and modulation of the gut microbiota. Methods Mice were fed with high-fat diets (HFD) for 20 weeks, in which experimental groups were pretreated with quadruple antibiotics and then given the corresponding bacterial solution or PBS. The expression of the glycolipid metabolism indicators, liver, and intestinal farnesol X receptors (FXR), and intestinal mucosal tight junction proteins were detected. We also analyzed the alterations of inflammatory and immune status and the gut microbiota of mice. Results Both strains were able to attenuate mass gain ( p <0.001), insulin resistance ( p <0.001), and liver lipid deposition ( p <0.001). They also reduced the levels of the pro-inflammatory factors ( p <0.05) and the proportion of Th17 ( p <0.001), while elevating the proportion of Treg ( p <0.01). Both strains activated hepatic FXR while suppressing intestinal FXR ( p <0.05), and elevating tight junction protein expression ( p <0.05). We also perceived changes in the gut microbiota and found both strains were able to synergize beneficial microbiota to function. Conclusions Administration of A. muciniphila or B. bifidum alone or in combination was protective against HFD-induced NAFLD formation and could be used as alternative treatment strategy for NAFLD after further exploration.
研究领域:
微生物学
·
肝病学
·
营养学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 21
·11070-11082
·
IF 6.317
Xuan Li,Yuting Ren,Guowen Huang,Ruofan Zhang,Yanan Zhang,Weiyun Zhu,Kaifan Yu
Succinate is produced by both the host and microbiota with pleiotropic functions in the modulation of intestinal inflammation and metabolic homeostasis, but the mechanisms remain elusive. This study aimed to determine whether dietary succinate influences the intestinal inflammatory response and to analyze the possible mechanisms by which succinate regulates enterohepatic metabolism. Sixteen growing barrows were randomly assigned to two groups, fed with a basal diet that consisted of a typical commercial diet or fed with a basal diet supplemented with 1% sodium succinate. Our data showed that dietary succinate activated the expression of succinate receptor 1 (SUCNR1) and increased the concentrations of pro-inflammatory cytokines in the intestine. Dietary succinate inhibited the expression levels of the ileal Farnesol X receptor (FXR) and its target genes, promoted hepatic bile acid secretion, and altered the bile acid metabolic profile. Then, we demonstrated that the pro-inflammatory cytokines triggered by succinate disrupted the ability of bile acids to activate FXR and fibroblast growth factor 19. Furthermore, dietary succinate reduced the abundance of bile-salt hydrolase enriched bacteria in the ileum. Taken together, dietary succinate activated the pro-inflammatory response via SUCNR1 in the intestine, and the pro-inflammatory cytokines induced by succinate blocked the activation of FXR and its target genes and disturbed bile acid enterohepatic circulation.
研究领域:
营养学
·
免疫学
·
代谢学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2019
·
IF 5.574
Rinkiko Suguro,Xiao-cong Pang,Zhong-wen Yuan,Si-yao Chen,Yi-Zhun Zhu,Ying Xie
Silybin (SB) is widely used to treat chronic liver diseases , especially this compound is much efficient for the treatments of alcoholic and non-alcoholic steatohepatitis (NASH). However, low bioavailability seriously limits wide-application of SB in biomedical niche. Prior to this study, we found that tangeretin (TG) could remarkably increase the bioavailability of SB by the inhibition of efflux transporters, which encourges us to therapeutical discovery of SB and TG combitional use against NASH. Here, we revealed that TG is capable of improving hepatic-protective activity of SB in mice with NASH by interfering liver oxidative stress, inflammation, and lipid accumulation. In addition, TG was observed to enhance the exposural level of SB in the plasma and liver of mice. Our metabolome assay confirmed that amino acid metabolism and lipid biosynthesis mostly accounted for combitional use of SB and TG to teat NASH in mice, basically biosynthesis of unsaturated fatty acids was mostly affected. Notably, significant inhibitions in fatty acid generating and transporting proteins such as G6PD, FABP4, LPL and CD36/FAT, and cholesterol metabolism enzyme CYP27A1 as well as nuclear transcription factors FXR , PPAR-γ, and LXR were illustrated to decipher therapeutic mechanisms of SB and TG against experimental NASH . Taken together, the strategy based combitional use of SB and TG has a potential-capacity to treat NASH.
研究领域:
肝病学
·
药理学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
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