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果寡糖通过色氨酸代谢物调节 Th17/Treg 细胞平衡来预防 OVA 诱导的小鼠食物过敏。

Fructooligosaccharides protect against OVA-induced food allergy in mice by regulating the Th17/Treg cell balance using tryptophan metabolites.

机构信息

Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.

出版信息

Food Funct. 2021 Apr 7;12(7):3191-3205. doi: 10.1039/d0fo03371e. Epub 2021 Mar 18.

Abstract

Fructooligosaccharides (FOS) can change gut microbiota composition and play a protective role in food allergy (FA). Furthermore, the protective mechanism of FOS against FA is unclear. In this study, intestinal flora and tryptophan (Trp) metabolites were investigated in a mouse model with FA supplemented with FOS. Meanwhile, we injected aryl hydrocarbon receptor antagonists (AhR-A) into a mouse model of FA supplemented with FOS to investigate whether T helper cell (Th) 17/regulatory T (Treg) cell balance was affected. Our research studies showed that dietary intake of FOS provided moderate protection from the intestinal inflammation induced by ovalbumin (OVA). This protective effect disappeared in AhR-A mice. The OVA mice manifestations had significantly lower bacterial richness, when compared to the normal control (NC) mice. Among fecal bacteria, the abundance of Akkermansiaceae (family level) and Verrucomicrobia (phylum level) increased and Ruminococcacere (phylum level) decreased in the feces of allergic mice. These changes were reversed by FOS treatment. FOS modulated the gut microbiome profiles that were altered in OVA mice, which showed an increase in the abundance of Ruminococcacere (phylum level) and a decrease in the abundance of Akkermansiaceae (family level) and Verrucomicrobia (phylum level). Liquid chromatography/tandem mass spectrometry (LC-MS/MS) analysis of Trp metabolites showed significant reductions in the level of kynurenine (kyn) in the serum of OVA mice, as compared to NC and FOS mice. Conversely, the levels of Trp and 5-hydroxytryptamine (5-HT) were significantly increased in OVA mice. Correlation analysis revealed a negative relationship between the relative abundance of Verrucomicrobiae (class level) and Akkermansiaceae (family level) with kyn, and a positive relationship with 5-HT. FOS significantly reduced interleukin-17A (IL-17A) and retinoic acid-associated nuclear orphan receptor-γt (RORγt) in FOS mice but not in AhR-A mice. FOS increased the level of interleukin-10 (IL-10) and Forkhead box P3 (Foxp3) in FOS mice but not in AhR-A mice. These findings suggest that FOS ameliorates allergic symptoms and impacts Th17/Treg balance in mice by modulating the gut microbiota composition and Trp metabolites. FOS may serve as an effective tool for the treatment of FA by regulating immune and gut microbiota.

摘要

低聚果糖(FOS)可以改变肠道微生物组成,并在食物过敏(FA)中发挥保护作用。此外,FOS 对 FA 的保护机制尚不清楚。在这项研究中,我们在 FA 补充 FOS 的小鼠模型中研究了肠道菌群和色氨酸(Trp)代谢物。同时,我们向 FA 补充 FOS 的小鼠模型中注射了芳烃受体拮抗剂(AhR-A),以研究 Th17/Treg 细胞平衡是否受到影响。我们的研究表明,饮食摄入 FOS 可提供对卵清蛋白(OVA)诱导的肠道炎症的适度保护。这种保护作用在 AhR-A 小鼠中消失了。与正常对照组(NC)相比,OVA 小鼠的粪便中细菌丰富度显著降低。在粪便细菌中,阿克曼菌科(科水平)和疣微菌科(门水平)的丰度增加,而过敏小鼠粪便中的真杆菌科(门水平)减少。这些变化在 FOS 治疗后得到逆转。FOS 调节了 OVA 小鼠中改变的肠道微生物组谱,显示真杆菌科(门水平)的丰度增加,阿克曼菌科(科水平)和疣微菌科(门水平)的丰度降低。色氨酸代谢物的液相色谱/串联质谱(LC-MS/MS)分析显示,与 NC 和 FOS 小鼠相比,OVA 小鼠血清中犬尿酸(kyn)水平显著降低。相反,OVA 小鼠的色氨酸和 5-羟色胺(5-HT)水平显著升高。相关性分析显示,Verrucomicrobiae(纲水平)和阿克曼菌科(科水平)的相对丰度与 kyn 呈负相关,与 5-HT 呈正相关。FOS 显著降低了 FOS 小鼠中的白细胞介素-17A(IL-17A)和维甲酸相关孤儿核受体-γt(RORγt),但在 AhR-A 小鼠中没有。FOS 增加了 FOS 小鼠中的白细胞介素-10(IL-10)和叉头框 P3(Foxp3)水平,但在 AhR-A 小鼠中没有。这些发现表明,FOS 通过调节肠道微生物组成和色氨酸代谢物来改善过敏症状并影响 Th17/Treg 平衡。FOS 可能通过调节免疫和肠道微生物群成为 FA 治疗的有效工具。

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