Department of General Surgery, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China.
Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China.
J Affect Disord. 2024 Sep 1;360:15-25. doi: 10.1016/j.jad.2024.05.119. Epub 2024 May 25.
This study uses a two-sample Mendelian randomization (MR) analysis to delineate the causal influence of gut microbiota on the occurrence of irritable bowel syndrome (IBS), concurrently assessing the potential mediating function of depression within this framework.
Several two-sample MR methods were used to assess the causal repercussions of gut microbiota on the onset of both IBS and depression. Following this, gut microbiota and depression, which demonstrated notable causal associations, were integrated as exposure variables in a multivariable Mendelian randomization (MVMR) framework to construct a model encompassing gut microbiota, depression, and IBS. Mediation effects were assessed by examining the indirect pathway of gut microbiota → depression → IBS.
Two-sample MR analysis unveiled a statistically significant causal association (P < 0.05) between specific bacterial group within the gut microbiota, notably p_Actinobacteria(OR = 0.829225), c_Clostridia(OR = 0.798897), s_Desulfovibrio_piger(OR = 1.163912), g_Streptococcus(OR = 1.132735), c_Actinobacteria(OR = 0.829224), and the onset of IBS. In the MVMR analysis, the relationship between depression and IBS was significant across Model 3, Model 7, Model 8, and Model 13 (P < 0.05). Assessment of mediation effects revealed that c_Clostridia and o_Clostridiales indirectly impacted IBS through depression, with masking effect ratios of 168.46 % and 168.44 %, respectively.
These findings underscore a resilient causal association between the composition of gut microbiota and the initiation of IBS. Furthermore, depression serves as a mediator for particular groups of gut bacteria, thereby contributing to the development of IBS. These observations imply that interventions targeting mental health may potentially alleviate the risk of IBS onset attributable to adverse configurations of gut microbiota.
本研究采用两样本 Mendelian 随机化（MR）分析，阐明肠道微生物群对肠易激综合征（IBS）发生的因果影响，并在此框架内评估抑郁的潜在中介作用。
采用多种两样本 MR 方法评估肠道微生物群对 IBS 和抑郁发生的因果影响。随后，将具有显著因果关联的肠道微生物群和抑郁作为暴露变量纳入多变量 Mendelian 随机化（MVMR）框架，构建包含肠道微生物群、抑郁和 IBS 的模型。通过检查肠道微生物群→抑郁→IBS 的间接途径来评估中介效应。
两样本 MR 分析揭示了肠道微生物群中特定细菌群与 IBS 发生之间存在统计学上显著的因果关联（P<0.05），其中 p_Actinobacteria（OR=0.829225）、c_Clostridia（OR=0.798897）、s_Desulfovibrio_piger（OR=1.163912）、g_Streptococcus（OR=1.132735）、c_Actinobacteria（OR=0.829224）与 IBS 的发生有关。在 MVMR 分析中，抑郁与 IBS 之间的关系在模型 3、模型 7、模型 8 和模型 13 中均具有统计学意义（P<0.05）。中介效应评估显示，c_Clostridia 和 o_Clostridiales 通过抑郁间接影响 IBS，其遮蔽效应比分别为 168.46%和 168.44%。
这些发现强调了肠道微生物群组成与 IBS 发生之间存在稳健的因果关联。此外，抑郁是特定肠道细菌群导致 IBS 发生的中介，表明针对心理健康的干预措施可能有助于降低因肠道微生物群不良构成而导致的 IBS 发病风险。
