PDF(Pubmed)
Abstract：
The interplay between gut microbiome genera and inflammatory kidney-related diseases, such as nephrotic syndrome, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease, has been observed. However, the causal relationships between specific bacterial genera and these renal diseases have not been fully elucidated.
To investigate the potential causal links between different genera of the gut microbiome and the susceptibility to various renal conditions utilizing two-sample Mendelian randomization (MR) analyses.
Genome-wide association study (GWAS) summary statistics of gut microbiota and inflammatory kidney-related diseases were obtained from published GWASs. Two-sample MR analyses were conducted using methods including inverse-variance weighted (IVW), MR Egger, and others to identify potential causal links between gut microbial genera and renal conditions. Sensitivity analyses, including Cochran\'s Q test and the MR-PRESSO global test, were performed to validate the robustness of the results and detect horizontal pleiotropy. In addition, a reverse MR analysis was conducted to assess reverse causation possibilities.
By synthesizing insights from both primary and sensitivity analyses, this study unveiled critical associations of 12 bacterial genera with nephrotic syndrome, 7 bacterial genera with membranous nephropathy, 3 bacterial genera with glomerulonephritis, 4 bacterial genera with acute tubulo-interstitial nephritis, 6 bacterial genera with chronic tubulo-interstitial nephritis, and 7 bacterial genera with chronic kidney disease. Various genera were pinpointed as having either positive or negative causal relationships with these renal conditions, as evidenced by specific ranges of IVW-OR values (all P< 0.05). The congruence of the sensitivity analyses bolstered the primary findings, displaying no marked heterogeneity or horizontal pleiotropy. Notably, the reverse MR analysis with nephritis as the exposure did not reveal any causal relationships, thereby strengthening the resilience and validity of the primary associations.
This study explored the causal associations between several gut microbial genera and the risk of several inflammatory kidney-related diseases, uncovering several associations between specific gut microbial genera and nephrotic syndrome, membranous nephropathy, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease. These findings enhance our understanding of the complex interplay between the gut microbiome and kidney diseases, and they will be beneficial for early diagnosis and subsequent treatment.
To investigate the potential causal links between different genera of the gut microbiome and the susceptibility to various renal conditions utilizing two-sample Mendelian randomization (MR) analyses.
Genome-wide association study (GWAS) summary statistics of gut microbiota and inflammatory kidney-related diseases were obtained from published GWASs. Two-sample MR analyses were conducted using methods including inverse-variance weighted (IVW), MR Egger, and others to identify potential causal links between gut microbial genera and renal conditions. Sensitivity analyses, including Cochran\'s Q test and the MR-PRESSO global test, were performed to validate the robustness of the results and detect horizontal pleiotropy. In addition, a reverse MR analysis was conducted to assess reverse causation possibilities.
By synthesizing insights from both primary and sensitivity analyses, this study unveiled critical associations of 12 bacterial genera with nephrotic syndrome, 7 bacterial genera with membranous nephropathy, 3 bacterial genera with glomerulonephritis, 4 bacterial genera with acute tubulo-interstitial nephritis, 6 bacterial genera with chronic tubulo-interstitial nephritis, and 7 bacterial genera with chronic kidney disease. Various genera were pinpointed as having either positive or negative causal relationships with these renal conditions, as evidenced by specific ranges of IVW-OR values (all P< 0.05). The congruence of the sensitivity analyses bolstered the primary findings, displaying no marked heterogeneity or horizontal pleiotropy. Notably, the reverse MR analysis with nephritis as the exposure did not reveal any causal relationships, thereby strengthening the resilience and validity of the primary associations.
This study explored the causal associations between several gut microbial genera and the risk of several inflammatory kidney-related diseases, uncovering several associations between specific gut microbial genera and nephrotic syndrome, membranous nephropathy, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease. These findings enhance our understanding of the complex interplay between the gut microbiome and kidney diseases, and they will be beneficial for early diagnosis and subsequent treatment.
摘要：
■肠道微生物群属与炎症性肾脏相关疾病之间的相互作用，比如肾病综合征，肾小球肾炎,肾小管间质性肾炎,和慢性肾病，已被观察到。然而,特定细菌属与这些肾脏疾病之间的因果关系尚未完全阐明。
■利用双样本孟德尔随机化（MR）分析，研究肠道微生物组不同属与各种肾脏疾病易感性之间的潜在因果关系。
■从已发表的GWAS中获得了肠道微生物群和炎性肾脏相关疾病的全基因组关联研究（GWAS）汇总统计。使用包括逆方差加权(IVW)在内的方法进行了双样本MR分析，Egger先生,和其他人来确定肠道微生物属和肾脏疾病之间的潜在因果关系。敏感性分析，包括Cochran的Q测试和MR-PRESSO全局测试，进行了验证结果的鲁棒性和检测水平多效性。此外,我们进行了反向MR分析,以评估反向因果关系的可能性.
■通过综合主要和敏感性分析的见解，这项研究揭示了12个细菌属与肾病综合征的关键关联，7种膜性肾病细菌属，3个细菌属与肾小球肾炎，4个细菌属急性肾小管间质性肾炎，慢性肾小管间质性肾炎的6个细菌属，和7个细菌属慢性肾病。各种属被确定为与这些肾脏疾病有正或负因果关系，IVW-OR值的特定范围证明了这一点（所有P<0.05）。敏感性分析的一致性支持了主要发现，显示没有标记的异质性或水平多效性。值得注意的是,以肾炎作为暴露的反向MR分析没有发现任何因果关系，从而加强主要协会的弹性和有效性。
这项研究探讨了几种肠道微生物属与几种炎症性肾脏相关疾病风险之间的因果关系，发现特定肠道微生物属与肾病综合征之间的几个关联，膜性肾病,肾小球肾炎,肾小管间质性肾炎,和慢性肾病。这些发现增强了我们对肠道微生物组和肾脏疾病之间复杂相互作用的理解。它们将有利于早期诊断和后续治疗。
■利用双样本孟德尔随机化（MR）分析，研究肠道微生物组不同属与各种肾脏疾病易感性之间的潜在因果关系。
■从已发表的GWAS中获得了肠道微生物群和炎性肾脏相关疾病的全基因组关联研究（GWAS）汇总统计。使用包括逆方差加权(IVW)在内的方法进行了双样本MR分析，Egger先生,和其他人来确定肠道微生物属和肾脏疾病之间的潜在因果关系。敏感性分析，包括Cochran的Q测试和MR-PRESSO全局测试，进行了验证结果的鲁棒性和检测水平多效性。此外,我们进行了反向MR分析,以评估反向因果关系的可能性.
■通过综合主要和敏感性分析的见解，这项研究揭示了12个细菌属与肾病综合征的关键关联，7种膜性肾病细菌属，3个细菌属与肾小球肾炎，4个细菌属急性肾小管间质性肾炎，慢性肾小管间质性肾炎的6个细菌属，和7个细菌属慢性肾病。各种属被确定为与这些肾脏疾病有正或负因果关系，IVW-OR值的特定范围证明了这一点（所有P<0.05）。敏感性分析的一致性支持了主要发现，显示没有标记的异质性或水平多效性。值得注意的是,以肾炎作为暴露的反向MR分析没有发现任何因果关系，从而加强主要协会的弹性和有效性。
这项研究探讨了几种肠道微生物属与几种炎症性肾脏相关疾病风险之间的因果关系，发现特定肠道微生物属与肾病综合征之间的几个关联，膜性肾病,肾小球肾炎,肾小管间质性肾炎,和慢性肾病。这些发现增强了我们对肠道微生物组和肾脏疾病之间复杂相互作用的理解。它们将有利于早期诊断和后续治疗。
