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HMGN2与组蛋白H1.2:一种新型益生菌混合物治疗季节性变应性鼻炎的潜在靶点

HMGN2 and Histone H1.2: potential targets of a novel probiotic mixture for seasonal allergic rhinitis.

作者信息

Li Lisha, Wen Xueyi, Gong Yiyi, Chen Yuling, Xu Jiatong, Sun Jinlyu, Deng Haiteng, Guan Kai

机构信息

Department of Allergy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

出版信息

Front Microbiol. 2023 Oct 6;14:1202858. doi: 10.3389/fmicb.2023.1202858. eCollection 2023.

Abstract

BACKGROUND

Allergic rhinitis (AR) is a common nasal inflammatory disorder that severely affects an individual's quality of life (QoL) and poses a heavy financial burden. In addition to routine treatments, probiotic intervention has emerged as a promising strategy for preventing and alleviating allergic diseases. The main objective of this study was to determine the effect of a novel multi-strain probiotic mixture on AR symptoms and investigate potential targets underlying the probiotic intervention.

METHODS

A randomized, double-blind, placebo-controlled clinical study was conducted on AR patients who were allergic to autumnal pollens ( = 31). Placebo or a novel probiotic mixture, composed of HN001, NCFM, Bi-07, LPC-37, and LE16, was administered after 2 months. The therapeutic efficacy was evaluated by a symptom assessment scale. Before and during the pollen season, blood samples were collected, and peripheral blood mononuclear cells (PBMCs) were isolated for further tandem mass tags (TMTs)-based quantitative proteomic analyses. Potential targets and underlying pathological pathways were explored using bioinformatics methods.

RESULTS

During the pollen season, the rhinoconjunctivitis symptom score of participants who were administered probiotics (probiotic group, = 15) was significantly lower than those administered placebo (placebo group, = 15) ( = 0.037). The proteomic analyses identified 60 differentially expressed proteins (DEPs) in the placebo group, and subsequent enrichment analyses enriched a series of pathways and biological processes, including signaling pathways of inflammation, coagulation cascade, lipid, carbohydrate and amino acid metabolic pathways, and transcription and translation processes. Least Absolute Shrinkage and Selection Operator (LASSO) regression extracted five main elements, namely, GSTO1, ATP2A2, MCM7, PROS1, and TRIM58, as signature proteins. A total of 17 DEPs were identified in the probiotic group, and there was no pathway enriched. Comparison of DEPs in the two groups revealed that the expression levels of the high-mobility group nucleosome-binding domain-containing protein 2 (HMGN2) and Histone H1.2 presented an opposite trend with different interventions.

CONCLUSION

Our data showed that AR symptoms alleviated after treatment with the novel multi-strain probiotic mixture, and the proteomic analyses suggested that HMGN2 and Histone H1.2 might be targets of probiotic intervention for seasonal AR.

摘要

背景

变应性鼻炎(AR)是一种常见的鼻腔炎症性疾病,严重影响个体的生活质量(QoL)并带来沉重的经济负担。除常规治疗外,益生菌干预已成为预防和缓解变应性疾病的一种有前景的策略。本研究的主要目的是确定一种新型多菌株益生菌混合物对AR症状的影响,并探究益生菌干预的潜在靶点。

方法

对31例对秋季花粉过敏的AR患者进行了一项随机、双盲、安慰剂对照的临床研究。2个月后给予安慰剂或由嗜酸乳杆菌HN001、鼠李糖乳杆菌NCFM、双歧杆菌Bi-07、植物乳杆菌LPC-37和副干酪乳杆菌LE16组成的新型益生菌混合物。通过症状评估量表评估治疗效果。在花粉季节之前和期间采集血样,分离外周血单个核细胞(PBMC)用于进一步基于串联质谱标签(TMT)的定量蛋白质组学分析。使用生物信息学方法探索潜在靶点和潜在病理途径。

结果

在花粉季节期间,接受益生菌治疗的参与者(益生菌组,n = 15)的鼻结膜炎症状评分显著低于接受安慰剂治疗的参与者(安慰剂组,n = 15)(P = 0.037)。蛋白质组学分析在安慰剂组中鉴定出60种差异表达蛋白(DEP),随后的富集分析富集了一系列途径和生物学过程,包括炎症信号通路、凝血级联反应、脂质、碳水化合物和氨基酸代谢途径以及转录和翻译过程。最小绝对收缩和选择算子(LASSO)回归提取了五个主要元素,即谷胱甘肽S-转移酶O1(GSTO1)、肌浆网Ca2+-ATP酶2(ATP2A2)、微小染色体维持蛋白7(MCM7)、蛋白S1(PROS1)和三聚体基序蛋白58(TRIM58)作为特征蛋白。在益生菌组中鉴定出总共17种DEP,且没有富集的途径。两组DEP的比较显示,含高迁移率族核小体结合域蛋白2(HMGN2)和组蛋白H1.2的表达水平在不同干预下呈现相反趋势。

结论

我们的数据表明,用新型多菌株益生菌混合物治疗后AR症状得到缓解,蛋白质组学分析表明HMGN2和组蛋白H1.2可能是季节性AR益生菌干预的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a0a/10588638/457ee146a5ae/fmicb-14-1202858-g0001.jpg

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