{"title":"肠道菌群产生的较高血浆戊酸盐水平可能对肾功能有有益影响。","authors":"Mohsen Mazidi, Niki Katsiki, Maciej Banach","doi":"10.1080/07315724.2019.1664955","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Observational studies have evaluated the relationships among plasma short chain fatty acids (SCFA) produced by gut microbiota, renal function, and risk of chronic kidney disease (CKD). In the present study, Mendelian Randomization (MR) analysis was applied to obtain unconfounded estimates of the casual association of genetically determined plasma valerate (an SCFA) with kidney function and risk of CKD.</p><p><strong>Method: </strong>MR was performed by using summary-level data from the largest genome-wide association studies (GWAS) conducted on plasma valerate, CKD, and estimated glomerular filtration rate (eGFR; separately in diabetic and nondiabetic individuals). Inverse variance weighted method (IVW), weighted median-based method, MR-Egger, as well as MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied. Sensitivity analysis was conducted using the leave-one-out method.</p><p><strong>Results: </strong>No significant association was observed between plasma valerate and CKD (IVW: β = 0.234, <i>p</i> = 0.744). In contrast, plasma valerate was positively associated with eGFR in the total population (IVW: β = 0.049, <i>p</i> = 0.022) and among nondiabetic individuals (IVW: β = 0.058, <i>p</i> = 0.009), but not in the diabetic population (IVW: β = -0.052, <i>p</i> = 0.603). None of the estimated associations was subjected to significant level of heterogeneity. Furthermore, MR-PRESSO analysis did not show any chance of outlier for all estimates. The pleiotropy test, with very a negligible intercept and insignificant <i>p</i> value, also indicated no chance of pleiotropy for all of our estimations (all <i>p</i> > 0.539). The results of the MR-Robust Adjusted Profile Score were identical with the IVW estimates, highlighting again no possibility of pleiotropy. Results of the leave-one-out method demonstrated that the links were not driven by single-nucleotide polymorphisms.</p><p><strong>Conclusions: </strong>Individuals with higher plasma valerate levels had better renal function, defined by eGFR. This finding was observed in the total population and in nondiabetic subjects, but not in those with diabetes. Further research is needed to elucidate the links among plasma valerate, kidney function, and CKD.</p>","PeriodicalId":29768,"journal":{"name":"Journal of the American Nutrition Association","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Higher Plasma Levels of Valerate Produced by Gut Microbiota May Have a Beneficial Impact on Renal Function.\",\"authors\":\"Mohsen Mazidi, Niki Katsiki, Maciej Banach\",\"doi\":\"10.1080/07315724.2019.1664955\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Observational studies have evaluated the relationships among plasma short chain fatty acids (SCFA) produced by gut microbiota, renal function, and risk of chronic kidney disease (CKD). In the present study, Mendelian Randomization (MR) analysis was applied to obtain unconfounded estimates of the casual association of genetically determined plasma valerate (an SCFA) with kidney function and risk of CKD.</p><p><strong>Method: </strong>MR was performed by using summary-level data from the largest genome-wide association studies (GWAS) conducted on plasma valerate, CKD, and estimated glomerular filtration rate (eGFR; separately in diabetic and nondiabetic individuals). Inverse variance weighted method (IVW), weighted median-based method, MR-Egger, as well as MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied. Sensitivity analysis was conducted using the leave-one-out method.</p><p><strong>Results: </strong>No significant association was observed between plasma valerate and CKD (IVW: β = 0.234, <i>p</i> = 0.744). In contrast, plasma valerate was positively associated with eGFR in the total population (IVW: β = 0.049, <i>p</i> = 0.022) and among nondiabetic individuals (IVW: β = 0.058, <i>p</i> = 0.009), but not in the diabetic population (IVW: β = -0.052, <i>p</i> = 0.603). None of the estimated associations was subjected to significant level of heterogeneity. Furthermore, MR-PRESSO analysis did not show any chance of outlier for all estimates. The pleiotropy test, with very a negligible intercept and insignificant <i>p</i> value, also indicated no chance of pleiotropy for all of our estimations (all <i>p</i> > 0.539). The results of the MR-Robust Adjusted Profile Score were identical with the IVW estimates, highlighting again no possibility of pleiotropy. Results of the leave-one-out method demonstrated that the links were not driven by single-nucleotide polymorphisms.</p><p><strong>Conclusions: </strong>Individuals with higher plasma valerate levels had better renal function, defined by eGFR. This finding was observed in the total population and in nondiabetic subjects, but not in those with diabetes. Further research is needed to elucidate the links among plasma valerate, kidney function, and CKD.</p>\",\"PeriodicalId\":29768,\"journal\":{\"name\":\"Journal of the American Nutrition Association\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2023-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the American Nutrition Association\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/07315724.2019.1664955\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NUTRITION & DIETETICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Nutrition Association","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/07315724.2019.1664955","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 1
摘要
目的:观察性研究评估了肠道微生物群产生的血浆短链脂肪酸(SCFA)、肾功能和慢性肾脏疾病(CKD)风险之间的关系。在本研究中,孟德尔随机化(MR)分析被应用于获得基因决定的血浆戊酸盐(SCFA)与肾功能和CKD风险的随机关联的无混淆估计。方法:通过使用最大的全基因组关联研究(GWAS)的汇总数据进行MR,该研究对血浆戊酸盐、CKD和估计的肾小球滤过率(eGFR;分别在糖尿病和非糖尿病个体中)。采用逆方差加权法(IVW)、加权中位数法、MR-Egger法、mr -多效性残差和离群值法(PRESSO)。采用留一法进行敏感性分析。结果:血浆戊酸盐与CKD无显著相关性(IVW: β = 0.234, p = 0.744)。相比之下,血浆戊酸盐与eGFR在总人口(IVW: β = 0.049, p = 0.022)和非糖尿病人群(IVW: β = 0.058, p = 0.009)中呈正相关,但在糖尿病人群中没有(IVW: β = -0.052, p = 0.603)。所有估计的关联都不存在显著的异质性。此外,MR-PRESSO分析并没有显示出所有估计值的异常值。多效性试验的截距可忽略不计,p值不显著,也表明我们所有的估计都没有多效性的机会(p均> 0.539)。MR-Robust调整后的评分结果与IVW的估计结果相同,再次强调不存在多效性的可能性。“留一”方法的结果表明,这些链接不是由单核苷酸多态性驱动的。结论:血浆戊酸盐水平较高的个体有较好的肾功能(由eGFR定义)。这一发现在总人口和非糖尿病患者中都有发现,但在糖尿病患者中没有发现。需要进一步的研究来阐明血浆戊酸盐、肾功能和CKD之间的联系。
Higher Plasma Levels of Valerate Produced by Gut Microbiota May Have a Beneficial Impact on Renal Function.
Objective: Observational studies have evaluated the relationships among plasma short chain fatty acids (SCFA) produced by gut microbiota, renal function, and risk of chronic kidney disease (CKD). In the present study, Mendelian Randomization (MR) analysis was applied to obtain unconfounded estimates of the casual association of genetically determined plasma valerate (an SCFA) with kidney function and risk of CKD.
Method: MR was performed by using summary-level data from the largest genome-wide association studies (GWAS) conducted on plasma valerate, CKD, and estimated glomerular filtration rate (eGFR; separately in diabetic and nondiabetic individuals). Inverse variance weighted method (IVW), weighted median-based method, MR-Egger, as well as MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied. Sensitivity analysis was conducted using the leave-one-out method.
Results: No significant association was observed between plasma valerate and CKD (IVW: β = 0.234, p = 0.744). In contrast, plasma valerate was positively associated with eGFR in the total population (IVW: β = 0.049, p = 0.022) and among nondiabetic individuals (IVW: β = 0.058, p = 0.009), but not in the diabetic population (IVW: β = -0.052, p = 0.603). None of the estimated associations was subjected to significant level of heterogeneity. Furthermore, MR-PRESSO analysis did not show any chance of outlier for all estimates. The pleiotropy test, with very a negligible intercept and insignificant p value, also indicated no chance of pleiotropy for all of our estimations (all p > 0.539). The results of the MR-Robust Adjusted Profile Score were identical with the IVW estimates, highlighting again no possibility of pleiotropy. Results of the leave-one-out method demonstrated that the links were not driven by single-nucleotide polymorphisms.
Conclusions: Individuals with higher plasma valerate levels had better renal function, defined by eGFR. This finding was observed in the total population and in nondiabetic subjects, but not in those with diabetes. Further research is needed to elucidate the links among plasma valerate, kidney function, and CKD.