# Glycomic Modulation of Gut Microbiome During HIV Infection

> **NIH NIH R01** · WISTAR INSTITUTE · 2021 · $806,565

## Abstract

PROJECT SUMMARY: An emerging paradigm suggests that gut glycosylation is a key force in maintaining a
homeostatic relationship between the gut and its microbiota. Nevertheless, it is unclear how host glycosylation
machinery contributes to HIV-associated microbial translocation and inflammation. Our published data show that
the host circulating glycome is altered in HIV+ individuals, and that these changes persist despite antiretroviral
therapy (ART). In particular, we observe a persistent HIV-associated loss of sialic acid (hypo-sialylation) from
plasma glycoproteins. This suggested to us that HIV infection may also be associated with glycomic alterations
in other body compartments, including the gut. We therefore used ileum and sigmoid colon biopsies from 20
HIV+ ART-suppressed individuals and found that gut glycomic patterns are indeed associated with distinct
microbial compositions, markers of inflammation, and HIV persistence. In particular, we found that: (1) Increased
levels of mucosal-associated, hypo-sialylated O glycans correlated with a dysbiotic and less diverse gut
microbiome, higher plasma levels of inflammatory markers, and higher levels of ileum-associated HIV DNA.
These data are intriguing because non-HIV studies show that sialic acid catabolism (removal, via sialidase)
drives microbial dysbiosis/translocation and intestinal inflammation. (2) Increased levels of fucosylated glycans
correlated with higher microbiome diversity, lower dysbiosis, and lower inflammation. These correlations are
consistent with reports, in the general population, that gut fucosylation sustains host-commensal symbiosis and
prevents gut inflammation by suppressing bacterial virulence genes. We hypothesize that HIV infection causes
persistent gut glycomic alterations – mainly hypo-sialylation and lack of proper fucosylation (dys-fucosylation) –
that alter microbiome composition, leading to microbial translocation, inflammation, and HIV persistence.
In Aim 1A, we will determine the impact of SIV infection on the gut glycome and the effects of this impact on
microbiome composition and function, inflammation, and viral persistence, using longitudinal samples from 18
pig-tailed macaques. We will also test the mechanistic hypothesis that enhanced activity of gut sialidase, and/or
increased expression of fucose-regulated bacterial virulence genes, contribute to SIV-associated microbial
translocation. In Aim 1B, we will determine the impact of ART-treated HIV infection on the gut glycome, using
cross-sectional samples from 40 HIV+ ART-suppressed individuals and well-matched HIV- controls. In Aim 2
and based on non-HIV studies demonstrating that sialidase inhibitor or L-fucose reduces microbial translocation
and gut inflammation, we will test the hypothesis that treatment with sialidase inhibitor or L-fucose would reduce
SIV-mediated microbial translocation and inflammation using SIV+ ART+ macaques. Our work aims to create a
new paradigm, namely that host glycosyla...

## Key facts

- **NIH application ID:** 10077287
- **Project number:** 5R01DK123733-02
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Mohamed Abdel Mohsen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $806,565
- **Award type:** 5
- **Project period:** 2019-12-24 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077287

## Citation

> US National Institutes of Health, RePORTER application 10077287, Glycomic Modulation of Gut Microbiome During HIV Infection (5R01DK123733-02). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10077287. Licensed CC0.

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