# The role of brain-gut microbiome interactions in mediating IBS and constipation symptoms during menses and menopause

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $482,048

## Abstract

ABSTRACT
Irritable bowel syndrome (IBS) and chronic (functional) constipation have a worldwide prevalence of 11.2% and
14%, respectively and are more common in women than men. However, the pathophysiology of IBS and
normal transit constipation (the largest subtype of chronic constipation) is incompletely understood and this
likely contributes to the fact that treatments are only efficacious in a subset of patients. Significant sex-related
differences include increased severity of gastrointestinal (GI) symptoms in women compared to men and
during menopause and in the premenses and menses phase of the menstrual cycle which are states of
depleted or declining estrogen. Based on previous studies and our preliminary data, our general hypotheses
are: 1) IBS symptom severity in female IBS increases during times of low or declining estrogen states, namely
in menopause and mid to late-luteal phase of the menstrual cycle, and is due to reduced estrogen-dependent
corticolimbic inhibition of emotional arousal networks, resulting in enhanced visceral perception. Alterations in
circulating gut microbial metabolites, in particular tryptophan, estrogen, and bile acids affecting brain stem
nuclei may play an additional role, and 2) The increased prevalence and severity of normal transit constipation
in women (in the absence of changes in transit or defecation), is due to altered perception of normal, non-
noxious afferent signals from the colon resulting from altered central processing. This is due to widespread
changes in sensorimotor, salience, and emotional arousal networks and is in part related to increased input
from ascending arousal systems originating in brainstem nuclei. Changes in the activity of and ascending
projections from these brainstem nuclei may be related in part to the influence of gut microbial metabolites and
of estrogen. We will test these hypotheses in two specific aims in which we will measure the relative
abundance of gut microbial taxa (16S rRNA), total microbial gene content (shotgun metagenomics), plasma
and fecal metabolites (commercial metabolomic platform), and multimodal brain MRI (functional resting state
connectivity and pain threat evoked responses) in female subjects: 1) Compare GI symptoms and BGM
interactions in premenopausal and postmenopausal female IBS and healthy controls (HCs) and 2) Compare
BGM interactions in premenopausal females with normal transit constipation with slow transit constipation and
HCs. We anticipate that our findings will identify novel endophenotypes that can lead to the development of
novel treatment approaches.

## Key facts

- **NIH application ID:** 9854645
- **Project number:** 1U54DK123755-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Lin Chang
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $482,048
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854645

## Citation

> US National Institutes of Health, RePORTER application 9854645, The role of brain-gut microbiome interactions in mediating IBS and constipation symptoms during menses and menopause (1U54DK123755-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9854645. Licensed CC0.

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