# Gut microbiome effects on intestinal barrier function and metabolic syndrome in HIV positive men who have sex with men

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $690,739

## Abstract

Project Summary/Abstract
Metabolic syndrome (MS), characterized by a cluster of conditions including dyslipidemia, central abdominal
obesity, insulin resistance, and high blood pressure, is prevalent in people living with HIV (PLWH), and puts
them at greater risk of cardiovascular events. MS and related metabolic derangements have been strongly
correlated with gut microbiome activity outside the context of HIV but has not been deeply explored in HIV
infected or uninfected men who have sex with men (MSM), who have a highly altered gut microbiome
composition. Intestinal dysbiosis, compromised intestinal barrier integrity and associated inflammation has
been linked with MS in certain populations, but whether this is a driving factor of high levels of MS in HIV+
MSM has not been deeply explored, even though increased bacterial translocation and associated systemic
inflammation is known to occur in PLWH. In our ongoing studies of factors that influence metabolic disease
across HIV+ and HIV negative MSM, we found elevated plasma lipopolysaccharide binding protein (LBP) to be
the most important predictor of poor metabolic health, with network analysis showing that LBP formed a hub
joining correlated microbial and immune predictors of poor metabolic health. Our results suggest a central role
of inflammatory processes linked with barrier dysfunction in the development of MS in HIV+ MSM, but further
mechanistic studies are needed to fully understand how barrier function is compromised, including a potential
role for gut bacteria and bacterial-derived metabolites, which are well known to influence barrier. One key
finding of our ongoing work was a negative correlation between plasma LBP levels and butyrate-producing
bacteria; Butyrate has a well-characterized protective influence on intestinal epithelial integrity. We also
observed a positive correlation between LBP and a microbe that degrades sialic acids on mucus glycoproteins,
which has also been linked with intestinal barrier dysfunction and inflammatory processes in PLWH previously.
Thus, we hypothesize that intestinal dysbiosis impacts gut barrier function in HIV+ MSM, and that this
promotes MS via the translocation of microbial products including LPS. To test this hypothesis, we will
perform three coordinated specific aims. In Aim 1 we will determine whether intestinal barrier dysfunction is
higher in HIV+ and negative MSM with MS compared to without MS and related to deficiency in butyrate-
production and/or activity of mucolytic bacteria in the gut microbiome. In Aims 2 and 3 we will verify the
relationship between HIV/MS-associated gut microbes and barrier dysfunction using enteroides and
gnotobiotic mice, and explore the role of microbial production of butyrate and degradation of mucus
glycoproteins in these processes. Taken together this work will produce a mechanistic understanding of the
relationship between gut microbiome dysbiosis, barrier function, and MS in HIV-infected individuals and wil...

## Key facts

- **NIH application ID:** 10674923
- **Project number:** 5R01DK131581-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Sean P Colgan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $690,739
- **Award type:** 5
- **Project period:** 2022-08-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10674923

## Citation

> US National Institutes of Health, RePORTER application 10674923, Gut microbiome effects on intestinal barrier function and metabolic syndrome in HIV positive men who have sex with men (5R01DK131581-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10674923. Licensed CC0.

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