# HIV-associated gut microbiome affects lung immunity and pneumococcal immune response

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $469,489

## Abstract

Summary:
Enteric commensal bacteria impact immune function not only in the intestine, but also at peripheral sites
including the lung. In mice, perturbations to the enteric microbiota, whether induced by a “germ free” state,
antibiotics, or dietary modulation, results in altered lung/peripheral immunity. These distant effects include
differential susceptibility to Streptococcus pneumonia infection and antibody response to vaccination.
Translocated microbial products, such as short chain fatty acids (SCFAs) or capsular components, can signal
to immune cell populations at peripheral sites, in some cases systemically priming the innate immune system
to enhance pathogen responses. Mechanistic pathways for these distal effects have not been tested or
reproduced in humans, neither in healthy adults nor in those with altered immunity as in HIV infection. Indeed,
even with effective Antiretroviral Therapy (ART), the incidence of pneumococcal pneumonia and secondary
bloodstream infections remain substantially higher in HIV-infected individuals, due in part to compromised
pneumococcal-specific antibody response. Potentially contributing to these complications, the gut microbiota of
HIV-infected individuals is substantially altered. In this grant proposal, we will investigate the hypothesis that
the dysbiotic gut microbiota of HIV-infected subjects contributes to suppressed innate immune activation and
phagocytic capacity of Alveolar Macrophage (AM) and enhanced regulation by adaptive immunity, thereby
impairing systemic and lung mucosal response to pneumococcal antigen. We will investigate this hypothesis
in 3 Specific Aims. In SA1, we will characterize the relationship between gut microbes and their metabolites
and immune phenotype and function of AM and T cells in the lung of HIV-infected individuals and HIV-negative
controls using an integrated multi’omic approach. We hypothesize that particular gut microbiome compositions
and their products/metabolites, will be associated with suppressed activation of pathogen response pathways
and phagocytic activity of lung AMs and regulatory phenotypes of both AMs and T cell populations. In SA2, we
will investigate the impact of fecal transplantation from HIV-positive subjects on pulmonary immune responses
to S. pneumoniae infection using gnotobiotic mice. We hypothesize that fecal transplant of stool from HIV-
infected subjects versus controls into gnotobiotic mice alters immune phenotypes in the lung that parallel those
in humans and increases severity of S. pneumoniae infection. In SA3, we will examine the relationship
between pneumococcal vaccine-specific immune responses in blood and lung of ART-treated subjects and
fecal microbiota composition. We hypothesize gut microbiota composition and translocated bacterial
products/metabolites wil correlate with pneumococcal vaccine-specific immunity in blood and lung of HIV-
infected ART-treated subjects. If an association between the gut microbiome, lung immune phenoty...

## Key facts

- **NIH application ID:** 9938610
- **Project number:** 5R01HL138639-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Thomas B. Campbell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $469,489
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938610

## Citation

> US National Institutes of Health, RePORTER application 9938610, HIV-associated gut microbiome affects lung immunity and pneumococcal immune response (5R01HL138639-04). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9938610. Licensed CC0.

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