Wang Liping, Ding Yuyan, Tang Yu, Yang Mengqi, Yang Zhihui, Yang Xiao, Xia Jiazeng
Department of General Surgery, Institute of General Surgical Research, Jiangnan University Medical Center, Wuxi, China.
Department of General Surgery, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China.
BMC Neurol. 2025 Apr 30;25(1):191. doi: 10.1186/s12883-025-04207-3.
Several previous observational studies have shown that abnormal sphingomyelin metabolism may be implicated in the pathogenesis of Alzheimer's disease. To determine the causal relationship between sphingolipid abundance and gut microbiota abundance at the genetic level, we conducted a Mendelian randomization (MR) investigation.
We first used the TwoSampleMR and MRPRESSO packages for conducting two-sample MR studies. Second, we utilized random effect inverse variance weighting (IVW) as the principal method of analysis and used MR‒Egger, the weighted median, the simple mode and the weighted mode as supplementary methods. Finally, we performed tests for heterogeneity and horizontal pleiotropy. These analyses were also conducted to evaluate the impact of individual SNPs on the outcomes of our analysis. A Bonferroni-corrected threshold of p = 2.4e-4(0.05/211) was considered significant, and p values less than 0·05 were considered to be suggestive of an association.
The results showed that sphingolipid levels were suggestively associated with the abundance of 6 gut microbiota taxa. Specifically, two taxa were positively correlated with sphingolipid levels, including the family Alcaligenaceae (p = 0.006, OR 95% CI = 1.109 [1.030-1.194]) and the species Ruminococcus callidus (p = 0.034, OR 95% CI = 1.217 [1.015-1.460]). In contrast, negative correlations were observed with the abundances of 4 gut microbiota taxa, including the genus Flavonifractor (p = 0.026, OR 95% CI = 0.804 [0.663-0.974]), the genus Streptococcus (p = 0.014, OR 95% CI = 0.909 [0.842-0.981]), the species Bacteroides caccae (p = 0.037, OR 95% CI = 0.870 [0.763-0.992]), and the species Haemophilus parainfluenzae (p = 0.006, beta 95% CI = -0.269 [-0.462, -0.076]). The results presented a normal distribution, with no anomalous values, heterogeneity, or horizontal pleiotropic effects detected.
This two-sample MR study revealed a potential causal relationship between sphingomyelin levels and gut microbiota abundance.
先前的多项观察性研究表明，鞘磷脂代谢异常可能与阿尔茨海默病的发病机制有关。为了在基因水平上确定鞘脂丰度与肠道微生物群丰度之间的因果关系，我们进行了一项孟德尔随机化（MR）研究。
我们首先使用TwoSampleMR和MRPRESSO软件包进行两样本MR研究。其次，我们采用随机效应逆方差加权（IVW）作为主要分析方法，并使用MR-Egger、加权中位数、简单模式和加权模式作为补充方法。最后，我们进行了异质性和水平多效性检验。还进行了这些分析以评估单个单核苷酸多态性（SNP）对我们分析结果的影响。经Bonferroni校正的p = 2.4e-4（0.05/211）阈值被认为具有统计学意义，p值小于0.05被认为提示存在关联。
结果表明，鞘脂水平与6种肠道微生物分类群的丰度存在提示性关联。具体而言，有两个分类群与鞘脂水平呈正相关，包括产碱菌科（p = 0.006，优势比95%置信区间= 1.109 [1.030 - 1.194]）和Callidus瘤胃球菌（p = 0.034，优势比95%置信区间= 1.217 [1.015 - 1.460]）。相反，观察到与4种肠道微生物分类群的丰度呈负相关，包括黄酮分解菌属（p = 0.026，优势比95%置信区间= 0.804 [0.663 - 0.974]）、链球菌属（p = 0.014，优势比95%置信区间= 0.909 [0.842 - 0.981]）、粪便拟杆菌（p = 0.037，优势比95%置信区间= 0.870 [0.763 - 0.992]）和副流感嗜血杆菌（p = 0.006，β值95%置信区间 = -0.269 [-0.462, -0.076]）。结果呈正态分布，未检测到异常值、异质性或水平多效性效应。
这项两样本MR研究揭示了鞘磷脂水平与肠道微生物群丰度之间潜在的因果关系。
