Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：本研究使用两个样本的孟德尔随机化（MR）分析来描述肠道菌群对肠易激综合征（IBS）发生的因果影响，在此框架内同时评估抑郁症的潜在中介功能。
方法：使用几种双样本MR方法来评估肠道菌群对IBS和抑郁症发作的因果影响。在此之后,肠道菌群和抑郁症，这证明了显著的因果关联，在多变量孟德尔随机化（MVMR）框架中整合为暴露变量，以构建包含肠道微生物群的模型，抑郁症,和IBS。通过检查肠道微生物群→抑郁→IBS的间接途径来评估中介作用。
结果：双样本MR分析揭示了肠道微生物群内特定细菌群之间的统计学显着因果关系（P<0.05），特别是p_放线菌（OR=0.829225），c_梭菌（OR=0.798897），脱硫弧菌(OR=1.163912)，g_链球菌（OR=1.132735），c_放线菌(OR=0.829224)，和IBS的发作。在MVMR分析中，在模型3、模型7、模型8和模型13中,抑郁与IBS之间的关系显著(P<0.05)。调解效果评估显示c_Clostridia和o_Clostridiales通过抑郁间接影响IBS，掩蔽效果率为168.46%和168.44%，分别。
结论：这些发现强调了肠道微生物群组成与IBS起始之间的弹性因果关系。此外，抑郁症是特定肠道细菌群的媒介，从而促进IBS的发展。这些观察结果暗示，针对心理健康的干预措施可能会减轻肠道微生物群不利配置引起的IBS发作的风险。
方法：使用几种双样本MR方法来评估肠道菌群对IBS和抑郁症发作的因果影响。在此之后,肠道菌群和抑郁症，这证明了显著的因果关联，在多变量孟德尔随机化（MVMR）框架中整合为暴露变量，以构建包含肠道微生物群的模型，抑郁症,和IBS。通过检查肠道微生物群→抑郁→IBS的间接途径来评估中介作用。
结果：双样本MR分析揭示了肠道微生物群内特定细菌群之间的统计学显着因果关系（P<0.05），特别是p_放线菌（OR=0.829225），c_梭菌（OR=0.798897），脱硫弧菌(OR=1.163912)，g_链球菌（OR=1.132735），c_放线菌(OR=0.829224)，和IBS的发作。在MVMR分析中，在模型3、模型7、模型8和模型13中,抑郁与IBS之间的关系显著(P<0.05)。调解效果评估显示c_Clostridia和o_Clostridiales通过抑郁间接影响IBS，掩蔽效果率为168.46%和168.44%，分别。
结论：这些发现强调了肠道微生物群组成与IBS起始之间的弹性因果关系。此外，抑郁症是特定肠道细菌群的媒介，从而促进IBS的发展。这些观察结果暗示，针对心理健康的干预措施可能会减轻肠道微生物群不利配置引起的IBS发作的风险。
