Genetically Predicted Immune Cells Mediate the Association Between Gut Microbiota and Gastroesophageal Reflux Disease

IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
Jia Wang, Bojian Fei, Chao Wang
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引用次数: 0

Abstract

Background: Recent evidence increasingly acknowledges the close interrelationship between immunity and gut microbiota (GM) in humans. Furthermore, previous studies have demonstrated a strong correlation between GM and gastroesophageal reflux disease (GERD). However, the specific impact of GM on immune factors in GERD remains largely unexplored. Therefore, we conducted the Mendelian randomization (MR) analysis to investigate the precise causal relationships and underlying mechanisms linking GM, immunity, and GERD.

Method: We employed the mediation MR utilizing summary statistics derived from Genome-Wide Association Study (GWAS) data to investigate the causal effects of 207 taxa and 205 bacterial pathways on GERD. The analysis concentrated on 731 immune cell traits as potential mediators. The inverse variance weighted (IVW) approach was the primary analytical method. To ensure robustness, we employed additional MR methods, including Bayesian weighted MR (BWMR), MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. Furthermore, a series of sensitivity analyses, such as the Cochran’s Q test, leave-one-out test, MR-Egger intercept analysis, and MR-PRESSO test, were conducted to ensure the reliability and consistency of the findings.

Results: The study identified three taxa and eight bacterial pathways that exhibited a negative correlation with GERD. Mediation MR analyses indicated that four bacterial pathways influence GERD through four immune cell types acting as mediators. For instance, the “arginine, ornithine, and proline interconversion” pathway was implicated in reducing the risk of GERD via “PDL-1 on CD14- CD16+ monocyte” cells, with a total effect of −0.0484 and a mediation effect of −0.0093. Sensitivity analyses provided additional validation for the reliability of the MR findings.

Conclusion: Our study contributes evidence to the close causal relationship between the GM and GERD, emphasizing the possible role of immune cells as mediators. Future research should focus on developing microbiome-oriented therapeutic approaches for managing GERD.

Abstract Image

基因预测免疫细胞介导肠道微生物群与胃食管反流病之间的关系
背景:最近有越来越多的证据表明,人体免疫力与肠道微生物群(GM)之间存在密切的相互关系。此外,以往的研究也表明,肠道微生物群与胃食管反流病(GERD)之间存在密切的相关性。然而,GM 对胃食管反流病免疫因素的具体影响在很大程度上仍未得到探讨。因此,我们进行了孟德尔随机化(MR)分析,以研究 GM、免疫和胃食管反流病之间的确切因果关系和内在机制。 方法:我们利用从全基因组关联研究(GWAS)数据中提取的汇总统计量进行了中介MR分析,研究了207个类群和205个细菌通路对胃食管反流病的因果影响。分析集中于作为潜在中介因子的 731 个免疫细胞性状。反方差加权(IVW)方法是主要的分析方法。为确保稳健性,我们还采用了其他 MR 方法,包括贝叶斯加权 MR(BWMR)、MR-Egger、加权中值、加权模式和简单模式。此外,我们还进行了一系列敏感性分析,如 Cochran's Q 检验、leave-one-out 检验、MR-Egger 截距分析和 MR-PRESSO 检验,以确保研究结果的可靠性和一致性。 研究结果研究发现了与胃食管反流病呈负相关的三个类群和八个细菌通路。中介MR分析表明,四种细菌通路通过四种免疫细胞类型作为中介影响胃食管反流病。例如,"精氨酸、鸟氨酸和脯氨酸相互转化 "途径通过 "CD14- CD16+ 单核细胞上的 PDL-1 "细胞降低胃食管反流病的风险,总效应为-0.0484,中介效应为-0.0093。敏感性分析进一步验证了磁共振研究结果的可靠性。 结论我们的研究为全球机制与胃食管反流病之间的密切因果关系提供了证据,并强调了免疫细胞作为介质的可能作用。未来的研究应侧重于开发以微生物为导向的治疗方法来控制胃食管反流病。
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来源期刊
CiteScore
5.30
自引率
0.00%
发文量
274
审稿时长
3-8 weeks
期刊介绍: IJCP is a general medical journal. IJCP gives special priority to work that has international appeal. IJCP publishes: Editorials. IJCP Editorials are commissioned. [Peer reviewed at the editor''s discretion] Perspectives. Most IJCP Perspectives are commissioned. Example. [Peer reviewed at the editor''s discretion] Study design and interpretation. Example. [Always peer reviewed] Original data from clinical investigations. In particular: Primary research papers from RCTs, observational studies, epidemiological studies; pre-specified sub-analyses; pooled analyses. [Always peer reviewed] Meta-analyses. [Always peer reviewed] Systematic reviews. From October 2009, special priority will be given to systematic reviews. [Always peer reviewed] Non-systematic/narrative reviews. From October 2009, reviews that are not systematic will be considered only if they include a discrete Methods section that must explicitly describe the authors'' approach. Special priority will, however, be given to systematic reviews. [Always peer reviewed] ''How to…'' papers. Example. [Always peer reviewed] Consensus statements. [Always peer reviewed] Short reports. [Always peer reviewed] Letters. [Peer reviewed at the editor''s discretion] International scope IJCP publishes work from investigators globally. Around 30% of IJCP articles list an author from the UK. Around 30% of IJCP articles list an author from the USA or Canada. Around 45% of IJCP articles list an author from a European country that is not the UK. Around 15% of articles published in IJCP list an author from a country in the Asia-Pacific region.
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