# Effects of Vagal Dysfunction on Gastrointestinal and Inflammatory Pathways in HIV

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $847,498

## Abstract

Project summary
Chronic HIV infection produces pathologic inflammation which drives disease progression and contributes to
the development of serious co-morbid medical conditions, even in the setting of effective combination
antiretroviral therapy (CART); translocation of bacterial products across the gastrointestinal (GI) mucosa is a
major antigenic stimulus for this process. Our research focuses on how vagal dysfunction (VD), which occurs
commonly as part of HIV-associated neuropathy, affects GI and immune function in HIV. Our prior work has
shown that HIV+ individuals with VD have a high prevalence of small intestinal bacterial overgrowth (SIBO),
and that SIBO is associated with elevation of the pro-inflammatory cytokine IL-6, which predicts morbidity and
mortality in HIV. We have also demonstrated that treatment with the acetylcholinesterase inhibitor
pyridostigmine, reduces indirect markers of bacterial translocation (sCD14) and the pro-inflammatory cytokine
TNFα. The current proposal builds on this work, with the overarching goal of examining vagally-mediated GI
mechanisms which could contribute to chronic inflammation in individuals with well-controlled HIV. Specifically
we will seek to establish that small intestinal dysmotility and hypochlorhydria mediate the relationship between
VD and SIBO, and to describe the changes in the GI microbiome in PLWH with SIBO. We will also determine
whether VD is associated with elevations in IL-6 and TNFα independent of SIBO, establish to what degree the
strength of these relationships depend on the presence of HIV infection, and whether they are reversible using
pyridostigmine and/or non-invasive vagal nerve stimulation (nVNS). To achieve these aims, we will recruit 150
HIV+ participants who will undergo autonomic function tests for VD, hydrogen methane breath testing for
SIBO, Wireless Motility Capsule (WMC, Smartpill) testing for GI regional transit times and pH measurements,
oral and stool sample collection for characterization of the GI microbiome, and blood draw for quantification of
inflammatory biomarkers. HIV-negative controls (N=100) will undergo the same assessments. Then a subset
of 96 HIV+ participants will enter one of two eight-week interventional phases followed by repetition of the
same testing battery: 1) double-blind treatment with pyridostigmine vs. placebo (N=86), or 2) open label
treatment with non-invasive vagal nerve stimulation (N=10). These procedures will shed light on mechanisms
linking VD to immune dysregulation in HIV, and provide support for potential therapies.

## Key facts

- **NIH application ID:** 10356148
- **Project number:** 5R01DK122853-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Jessica Robinson-Papp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $847,498
- **Award type:** 5
- **Project period:** 2020-02-11 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356148

## Citation

> US National Institutes of Health, RePORTER application 10356148, Effects of Vagal Dysfunction on Gastrointestinal and Inflammatory Pathways in HIV (5R01DK122853-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10356148. Licensed CC0.

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