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）是最好的研究和最有效的治疗IBS， 靶向脑-肠-微生物组（BGM）轴，初步数据显示，这种治疗效果 这与脑干与其他大脑网络的连接减少以及相对 类杆菌属的丰度。女性IBS患病率的增加， 胃肠道疼痛状况，以及女性IBS对各种 内部和外部刺激（多感官敏感性）表明存在重要的性别差异， 一些BGM机制加州大学洛杉矶分校SCOR在以前的资助期间进行的研究 在女性IBS受试者中建立了CRF-蓝斑系统的反应性增加， 提示去甲肾上腺素能脑干系统在IBS病理生理学中起重要作用。在 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， 这些性效应的基础。基于这些初步数据，本项目的总体目标是将CBT作为一种 探索研究特定疾病相关的脑、脑干、肠道改变之间的关系 微生物组和症状结果，并确定性别差异在这些关系中的作用。我们将 研究男性和女性IBS患者在CBT或常规护理之前和之后，使用先进的神经成像技术， 总体SCOR的微生物组技术，以测试以下内容：目的A.将确定性别差异， CBT对脑干核团和脑网络之间以及这些网络之间的连接的影响 在休息和挑衅后。瞄准B。将确定CBT对肠道微生物组影响的性别差异 目标C将确定CBT结果的临床，大脑和肠道微生物组预测因子。

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.