G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.
David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Microbiome. 2021 Nov 30;9(1):236. doi: 10.1186/s40168-021-01188-6.
There is growing recognition that bidirectional signaling between the digestive tract and the brain contributes to irritable bowel syndrome (IBS). We recently showed in a large randomized controlled trial that cognitive behavioral therapy (CBT) reduces IBS symptom severity. This study investigated whether baseline brain and gut microbiome parameters predict CBT response and whether response is associated with changes in the brain-gut-microbiome (BGM) axis.
Eighty-four Rome III-diagnosed IBS patients receiving CBT were drawn from the Irritable Bowel Syndrome Outcome Study (IBSOS; ClinicalTrials.gov NCT00738920) for multimodal brain imaging and psychological assessments at baseline and after study completion. Fecal samples were collected at baseline and post-treatment from 34 CBT recipients for 16S rRNA gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acids. Clinical measures, brain functional connectivity and microstructure, and microbiome features associated with CBT response were identified by multivariate linear and negative binomial models.
At baseline, CBT responders had increased fecal serotonin levels, and increased Clostridiales and decreased Bacteroides compared to non-responders. A random forests classifier containing 11 microbial genera predicted CBT response with high accuracy (AUROC 0.96). Following treatment, CBT responders demonstrated reduced functional connectivity in regions of the sensorimotor, brainstem, salience, and default mode networks and changes in white matter in the basal ganglia and other structures. Brain changes correlated with microbiome shifts including Bacteroides expansion in responders.
Pre-treatment intestinal microbiota and serotonin levels were associated with CBT response, suggesting that peripheral signals from the microbiota can modulate central processes affected by CBT that generate abdominal symptoms in IBS. CBT response is characterized by co-correlated shifts in brain networks and gut microbiome that may reflect top-down effects of the brain on the microbiome during CBT. Video abstract.
越来越多的人认识到，消化道和大脑之间的双向信号传递有助于肠易激综合征（IBS）。我们最近在一项大型随机对照试验中表明，认知行为疗法（CBT）可降低 IBS 症状严重程度。本研究旨在探讨基线时大脑和肠道微生物组参数是否可预测 CBT 反应，以及反应是否与大脑-肠道-微生物组（BGM）轴的变化有关。
从肠易激综合征结局研究（IBSOS；ClinicalTrials.gov NCT00738920）中抽取 84 例符合罗马 III 标准的 IBS 患者，在基线和研究完成后进行多模态脑成像和心理评估。从 34 例接受 CBT 的患者中采集基线和治疗后粪便样本，进行 16S rRNA 基因测序、非靶向代谢组学和短链脂肪酸测量。通过多元线性和负二项式模型确定与 CBT 反应相关的临床指标、大脑功能连接和微观结构以及微生物组特征。
在基线时，与非反应者相比，CBT 反应者的粪便 5-羟色胺水平升高，梭状芽胞杆菌增多，拟杆菌减少。包含 11 个微生物属的随机森林分类器对 CBT 反应具有很高的准确性（AUROC 0.96）。治疗后，CBT 反应者的感觉运动、脑干、突显和默认模式网络区域的功能连接减少，基底节和其他结构的白质发生变化。大脑变化与微生物组变化相关，包括反应者中拟杆菌的扩张。
治疗前肠道微生物组和 5-羟色胺水平与 CBT 反应相关，提示来自微生物组的外周信号可以调节 CBT 影响的中枢过程，从而产生 IBS 的腹部症状。CBT 反应的特征是大脑网络和肠道微生物组的共同相关变化，这可能反映了 CBT 期间大脑对微生物组的自上而下影响。视频摘要。
