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Anaerobic bacterial fermentation products increase tuberculosis risk in antiretroviral-drug-treated HIV patients.
Open accessAbstract
Despite the immune-reconstitution with antiretroviral therapy (ART), HIV-infected individuals remain highly susceptible to tuberculosis (TB) and have an enrichment of oral anaerobes in the lung. Products of bacterial anaerobic metabolism, like butyrate and other short-chain fatty acids (SCFAs), induce regulatory T cells (Tregs). We tested whether SCFAs contribute to poor TB control in a longitudinal cohort of ART-treated HIV-infected South Africans. Increase in serum SCFAs was associated with increased TB susceptibility. SCFAs inhibited IFN-γ and IL-17A production in peripheral blood mononuclear cells from HIV-infected ART-treated individuals in response to M. tuberculosis antigen stimulation. Pulmonary SCFAs correlated with increased oral anaerobes, such as Prevotella in the lung, and with M. tuberculosis antigen-induced Tregs. Metabolites from anaerobic bacterial fermentation may, therefore, increase TB susceptibility by suppressing IFN-γ and IL-17A production during the cellular immune response to M. tuberculosis.
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“Previous research has shown that a large number of anaerobic bacteria originating from the oral cavity are present in the lungs of pulmonary tuberculosis patients, and bacterial metabolites (short-chain fatty acids) were associated with both the oral anaerobic bacterial load (e.g., Prevotella) and T-regs response (Segal et al., 2017).”
From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Segal et al., 2017
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“Previous research has shown that a large number of anaerobic bacteria originating from the oral cavity are present in the lungs of pulmonary tuberculosis patients, and bacterial metabolites (short-chain fatty acids) were associated with both the oral anaerobic bacterial load (e.g., Prevotella) and T-regs response (Segal et al., 2017).”
From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Segal et al., 2017
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Metadata
- Authors
- Segal, L. N., Clemente, J. C., Li, Y., Ruan, C., Cao, J., Danckers, M., Morris, A., Tapyrik, S., Wu, B. G., Diaz, P., Calligaro, G., Dawson, R., van Zyl-Smit, R. N., Dheda, K., Rom, W. N., & Weiden, M. D.
- Affiliations
- New York University (US)
- University of Michigan (US)
- University of Pittsburgh (US)
- The Ohio State University (US)
- University of Cape Town (ZA)
- Corresponding author
- Weiden, Michael D.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 21
- Issue
- 4
- Pages
- 530-537.e4
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC5465639
- OpenAlex
- W2602210733
- Cited by
- 160
- References
- 50
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 32 · 2023: 16 · 2022: 17 · 2021: 20 · 2020: 9 · 2019: 11 · 2018: 12 · 2017: 5
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIAID (P30CA016087, K23 AI102970, K24 AI080298A)
- NIH (RO1HL090316, U24 DK097153)
- Early Detection Research Network (5U01CA086137-13)
- Clinical and Translational Science Institute (UL1 TR000038)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Keywords
- tuberculosis, HIV, antiretroviral therapy, short-chain fatty acids, butyrate, regulatory T cells, oral anaerobes, Prevotella, Mycobacterium tuberculosis, interferon-gamma, IL-17A, cell-mediated immunity, lung microbiome, tuberculosis susceptibility
- MeSH terms
- Bacteria, Anaerobic, Disease Susceptibility, Fatty Acids, Volatile, Humans, Immunologic Factors, Interferon-gamma, Leukocytes, Mononuclear, Longitudinal Studies, Lung, Mycobacterium tuberculosis, South Africa, Tuberculosis, Pulmonary, HIV Infections, Interleukin-17, Anti-Retroviral Agents, T-Lymphocytes, Regulatory
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