Sex related differences in the effect of cognitive behavioral therapy on emotional arousal and salience circuits and the role of the gut microbiome

摘要 认知行为疗法(CBT)是对IBS研究最充分、最有效的治疗方法 靶向大脑-肠道-微生物组(BGM)轴，初步数据显示，这种治疗效果是 与脑干与其他脑网络的连通性降低以及相对 类杆菌类群的丰富。女性IBS患病率增加，非合并症发生率越高 胃肠道疼痛状况，以及女性IBS对各种药物的敏感性增加的较高患病率 内部和外部刺激(多感官敏感度)表明存在重要的性别差异 其中一些BGM机制。加州大学洛杉矶分校SCOR在之前的资助期间进行的研究 在女性IBS受试者中建立了CRF蓝斑系统增强的反应性， 提示去甲肾上腺素能脑干系统在IBS的病理生理学中起重要作用。在……里面 此外，我们早期的研究已经开始确定临床、功能和皮质脑机制，这些机制可能 这是这些性影响的基础。基于这些初步数据，该项目的总体目标是将CBT作为一种 探讨脑、脑干、肠道等特定疾病相关改变之间的关系 微生物组和症状结局，并确定性别差异在这些关系中的作用。我们会 使用先进的神经成像和常规护理技术对男性和女性IBS患者进行CBT或常规护理前后的研究 微生物组技术的整体SCOR测试如下：目标A.将在性别差异中识别 CBT对脑干核团和脑网络之间以及这些网络之间连接的影响 在休息时和在挑衅之后。目标B将确定CBT对肠道微生物群影响的性别差异 参数和目标C将确定CBT结果的临床、脑和肠道微生物组预测因素。

ABSTRACT Cognitive Behavioral Therapy (CBT) is the most well researched and most effective treatment for IBS that targets the brain-gut-microbiome (BGM) axis, and preliminary data show that this therapeutic effect is associated with a reduction of brainstem connectivity with other brain networks and a change in relative abundance of Bacteroides taxa. The increased prevalence of IBS in women, the higher rate of comorbid non- GI pain conditions, as well as the higher prevalence in female IBS of increased sensitivity to a variety of internal and external stimuli (multisensory sensitivity) suggest the presence of important sex differences in some of these BGM mechanisms. Research performed by the UCLA SCOR during previous funding has established an increased responsiveness of the CRF-Locus Coeruleus system in female IBS subjects, suggesting that this noradrenergic brainstem system plays an important role in IBS pathophysiology. In addition, our earlier research has begun to identify clinical, functional and cortical brain mechanisms that may underlie these sex effects. Based on these preliminary data, the overall goal of this Project is to use CBT as a probe to study the relationship between specific disease-related alterations of the brain, brainstem, the gut microbiome, and symptomatic outcome, and identify the role of sex differences in these relationships. We will study male and female IBS patients before and after CBT or usual care using the advanced neuroimaging and microbiome technologies of the overall SCOR to test the following: Aim A. will identify sex differences in the impact of CBT on the connectivity between brainstem nuclei and brain networks and between these networks at rest and after provocation. Aim B. will identify sex differences in the impact of CBT on gut microbiome parameters and Aim C will identify clinical, brain and gut microbiome predictors of CBT outcomes.