Jining No. 1 People's Hospital, Jining, Shandong, China.
Clinical Laboratory Department, Jiangnan University Medical Center, JUMC, Wuxi, Jiangsu, China.
Sci Rep. 2024 Nov 9;14(1):27418. doi: 10.1038/s41598-024-78996-x.
Immune system regulation is a key indicator of the gut microbiota (GM) influencing disease development. The causal role of the GM in Guillain-Barré syndrome (GBS) and whether it can be mediated by immune cells is unknown. Genome-wide association study (GWAS) summary statistics for the GM were obtained from the Dutch Microbiota Project (n = 7,738) and the FINRISK 2002 (FR02) cohort (n = 5,959). Inverse variance weighting method (IVW) were used as the main method to evaluate the causal relationship between GM and GBS. Subsequently, the mediating effects of 731 immune traits were evaluated. Additionally, we also executed the Bayesian Weighting algorithm for verification. Mendelian randomization (MR) analysis determined the protective effect of the pyrimidine deoxyribonucleoside degradation superpathway on GBS (IVW: P = 0.0019, OR = 0.4508). It is worth noting that in the causal effects of pyrimidine deoxyribonucleoside degradation superpathway on GBS, the mediated proportions of herpesvirus entry mediator (HVEM) ( HVEM on CM CD4 + , HVEM on naive CD4 + , HVEM on CD45RA - CD4 + , HVEM on CM CD8br) in the T cell maturation stage on GBS were -0.0398, -0.0452, -0.0414, -0.0425, accounting for 5.00%, 5.67%, 5.19% and 5.34% of the total effect. 11 types of intestinal bacteria might be involved in the pyrimidine deoxyriboside degradation superpathway, including Staphylococcus A fleurettii, AR31,CAG-274 sp000432155, Photobacterium, Acetobacteraceae, Dysgonomonadaceae, NK4A144,Leptospirae, CAG-81 sp000435795, Leptospirales and CAG-873 sp001701165. This study suggests that there is a causal relationship between pyrimidine deoxyribonucleoside degradation superpathway and GBS, which may be mediated by HVEM on CD4 + and CD8 + T cells. As a bidirectional molecular switch, HVEM plays an important role in T cell regulation. 11 intestinal flora were found to be involved in pyrimidine deoxyribonucleoside degradation superpathway, and their changes may be related to the occurrence of GBS. However, extensive research is still warranted before microbiome sequencing can be used for prevention and targeted treatment of GBS.
免疫系统调节是肠道微生物群（GM）影响疾病发展的一个关键指标。GM 在格林-巴利综合征（GBS）中的因果作用以及它是否可以通过免疫细胞介导尚不清楚。从荷兰微生物组计划（n=7738）和 FINRISK 2002（FR02）队列（n=5959）获得了 GM 的全基因组关联研究（GWAS）汇总统计数据。使用逆方差加权法（IVW）作为评估 GM 与 GBS 之间因果关系的主要方法。随后，评估了 731 种免疫特征的中介效应。此外，我们还执行了贝叶斯加权算法进行验证。孟德尔随机化（MR）分析确定嘧啶脱氧核苷降解超级途径对 GBS 的保护作用（IVW：P=0.0019，OR=0.4508）。值得注意的是，在嘧啶脱氧核苷降解超级途径对 GBS 的因果效应中，HVEM（CM CD4+上的 HVEM、幼稚 CD4+上的 HVEM、CD45RA-CD4+上的 HVEM、CM CD8br 上的 HVEM）在 T 细胞成熟阶段对 GBS 的中介比例分别为-0.0398、-0.0452、-0.0414、-0.0425，占总效应的 5.00%、5.67%、5.19%和 5.34%。11 种肠道细菌可能参与嘧啶脱氧核糖苷降解超级途径，包括金黄色葡萄球菌A fleurettii、AR31、CAG-274 sp000432155、Photobacterium、Acetobacteraceae、Dysgonomonadaceae、NK4A144、Leptospirae、CAG-81 sp000435795、Leptospirales 和 CAG-873 sp001701165。本研究表明，嘧啶脱氧核糖核苷降解超级途径与 GBS 之间存在因果关系，可能由 CD4+和 CD8+T 细胞上的 HVEM 介导。作为双向分子开关，HVEM 在 T 细胞调节中起着重要作用。发现 11 种肠道菌群参与嘧啶脱氧核糖核苷降解超级途径，其变化可能与 GBS 的发生有关。然而，在微生物组测序可用于 GBS 的预防和靶向治疗之前，仍需要广泛的研究。
