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

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $340,280

## Abstract

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.

## Key facts

- **NIH application ID:** 9854646
- **Project number:** 1U54DK123755-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** JENNIFER S LABUS
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,280
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854646

## Citation

> US National Institutes of Health, RePORTER application 9854646, Sex -related differences in structure, function and connectivity of central arousal and salience networks involving brainstem nuclei are involved in IBS symptom generation. (1U54DK123755-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9854646. Licensed CC0.

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