Sex -related differences in structure, function and connectivity of central arousal and salience networks involving brainstem nuclei are involved in IBS symptom generation.

涉及脑干核的中枢唤醒和显着网络的结构、功能和连接性方面的性别相关差异参与了 IBS 症状的产生。

• 批准号: 10688180
• 负责人: JENNIFER S LABUS
• 金额: $ 23.07万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688180
• 关键词: Abdominal Pain; Address; Afferent Pathways; Anatomy; Arousal; Behavioral; Bile Acids; Biological; Biological Markers; Brain; Brain Stem; Cell Nucleus; Characteristics; Chronic; Circulation; Classification; Clinical; Consensus; Data; Data Set; Databases; Development; Diagnostic Procedure; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Emotional; Enrollment; Estrogens; Female; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Generations; Goals; Habits; Health Care Costs; Hypersensitivity; Image; Imaging Techniques; Imaging technology; Intestinal Diseases; Intestines; Investigation; Irritable Bowel Syndrome; Kynurenine; Laboratories; MRI Scans; Machine Learning; Magnetic Resonance Imaging; Measurable; Measurement; Measures; Metagenomics; Multimodal Imaging; Neuronal Plasticity; Pain; Pathway interactions; Patients; Physiological; Plasma; Play; Pontine structure; Property; Public Health; Recurrence; Reporting; Research; Resolution; Rest; Role; Sensory; Sex Differences; Shotguns; Signal Transduction; Spinal; Stimulus; Stress; Structure; Symptoms; Testing; Tryptophan; Vertebral column; Volatile Fatty Acids; blood-brain barrier crossing; comorbidity; drug development; effective therapy; expectation; female sex hormone; gut microbiome; insight; learning network; male; metabolomics; microbial; multimodality; neural network; neuromelanin; novel; patient subsets; personalized intervention; recruit; sex; structural imaging; transcriptome sequencing; treatment strategy

ABSTRACT Irritable bowel syndrome (IBS) is a highly prevalent intestinal disorder characterized by chronically recurring abdominal pain and altered bowel habit. Despite extensive research efforts over the past few decades, there is no general consensus about the pathophysiology, the role of SABV in pathophysiology, nor are there been any reliable biomarkers for guiding treatment decisions. This lack of progress is reflected in the continued excessive direct and indirect health care costs generated by these conditions, largely due to unnecessary diagnostic procedures and lack of effective therapies. Increasing evidence supports a role of dysregulations within the brain-gut microbiome (BGM) axis in IBS. Therefore, the overall goal of this proposal is to determine the sex-specific role of distinct brainstem nuclei and their bidirectional interactions with several brain networks, of the gut, and of gut microbial metabolites and female sex hormones in symptom generation in IBS. To address this goal we will first characterize sex-specific functional and structural changes in the brain and brainstem using multimodal MRI (structural, DTI, functional MRI) in IBS patients and healthy control subjects (HCs). We will use machine learning and neural network approaches to identify a CNS signature from the imaging data for IBS by leveraging both the newly enrolled IBS subjects and our large existing database of functional and structural MRI scans in IBS and HCs. We will identify sex differences in cross sectional associations between functional and structural imaging measurements, gut microbial measures (RNA sequencing, shotgun metagenomics, metabolomics) and behavioral characteristics of IBS patients, with an emphasis on estrogen and tryptophan metabolites and short chain fatty acids. The information garnered from this study is expected to identify biologically based male and female patient subgroups, to reveal novel insights into the involvement of BGM interactions in IBS pathophysiology, in particular about the involvement of the brainstem and gut microbial metabolites, and to aid in the development of more effective treatment strategies in IBS.

摘要