# Identifying Gut Microbiome Mediated Mechanisms for Diastolic Dysfunction Improvement After Bariatric Surgery

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $446,632

## Abstract

Project Summary
Sleeve gastrectomy (SG), is a type of bariatric surgery, which improves obesity-related diastolic dysfunction, a
hallmark finding of heart failure with preserved ejection fraction (HFpEF). As weight reduction through dieting
and caloric restriction fails to improve cardiac function, this suggests a mechanism for diastolic function
improvement initiated from the alteration in gastrointestinal anatomy after SG. The broad, long-term objective
of this project is to explore if gut microbial changes after SG, lead to a bile acid pool rich in farnesoid X receptor
(FXR) agonists, that mediate diastolic function improvements. In Specific Aim 1, we will test the hypothesis that
the post-SG gut microbiome increases plasma bile acid FXR agonists as a mechanism for cardiac function
improvement. Studies will be conducted utilizing fecal material transfer of SG mice as well as metagenomic
sequence analysis of SG stool from rodents and humans to determine the transferable effect of the gut
microbiome on the plasma BA pool and diastolic function. In Specific Aim 2, we will determine whether SG
plasma decreases cardiomyocyte metabolic stress via FXR activation. Human and rodent cardiomyocyte cell
lines will be engineered for regulated FXR expression to determine whether SG plasma reduces cardiac
metabolic stress through FXR agonism. In Specific Aim 3, we will determine whether SG improves diastolic
function through cardiomyocyte FXR signaling in vivo by performing surgery and assessing cardiac function in a
cardiomyocyte-specific FXR knockout mouse model. We hypothesize that SG enhances FXR signaling through
microbial-derived products to improve cardiac function. These findings will enhance our understanding of the
mechanisms for diastolic recovery after bariatric surgery to develop novel surgical and non-surgical therapies for
diastolic dysfunction and HFpEF which replicate the metabolic mechanisms generated by a SG.

## Key facts

- **NIH application ID:** 10442822
- **Project number:** 1R01HL158900-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Tammy Lyn Kindel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $446,632
- **Award type:** 1
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442822

## Citation

> US National Institutes of Health, RePORTER application 10442822, Identifying Gut Microbiome Mediated Mechanisms for Diastolic Dysfunction Improvement After Bariatric Surgery (1R01HL158900-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10442822. Licensed CC0.

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