Anaerobic bacterial fermentation products increase tuberculosis risk in antiretroviral-drug-treated HIV patients.

Segal, Leopoldo N.; Clemente, Jose C.; Li, Yonghua; Ruan, Chunhai; Cao, Jane; Danckers, Mauricio; Morris, Alison; Tapyrik, Sarah; Wu, Benjamin G.; Diaz, Philip; Calligaro, Gregory; Dawson, Rodney; van Zyl-Smit, Richard N.; Dheda, Keertan; Rom, William N.; Weiden, Michael D.

doi:10.1016/j.chom.2017.03.003

Cited by 160Tuberculosis Research and EpidemiologyGut microbiota and healthInfectious Diseases and Tuberculosis

Anaerobic bacterial fermentation products increase tuberculosis risk in antiretroviral-drug-treated HIV patients.

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Segal, Leopoldo N., Clemente, Jose C., Li, Yonghua, Ruan, Chunhai, Cao, Jane, Danckers, Mauricio, Morris, Alison, Tapyrik, Sarah +8 more·2017·Cell Host & Microbe

DOI 10.1016/j.chom.2017.03.003PMC PMC5465639

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Abstract

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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A large number of anaerobic bacteria originating from the oral cavity are present in the lungs of pulmonary tuberculosis patients.
“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
Bacterial metabolites (short-chain fatty acids) are associated with both oral anaerobic bacterial load (e.g., Prevotella) and T-regs response.
“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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Ruiz-Briseño, M. D. R., Ratkovich-González, S., Álvarez-Zavala, M., Magaña, A. V., González-Hernández, L. A., Ramos‐Solano, M., & Andrade-Villanueva, J. F. (2019) · Poster presentations · doi:10.1136/sextrans-2019-sti.331
Latent tuberculosis infection shapes gut microbiome and immune-metabolic interactions in people living with HIV
Devadiga, P., Batgire, J., Karandikar, K., Bhowmick, S., Birje, S., Kerkar, S. C., Nagar, V. S., Patil, D. P., Agrawal, S. R., Shastri, J. S., et al. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2721739
Antiretroviral Treatment-Induced Decrease in Immune Activation Contributes to Reduced Susceptibility to Tuberculosis in HIV-1/Mtb Co-infected Persons
Wilkinson, K., Schneider-Luftman, D., Lai, R., Barrington, C., Jhilmeet, N., Lowe, D., Kelly, G., & Wilkinson, R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2021.645446 · Cited by 7 · see citing works

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: Segal, Leopoldo N.
Li, Yonghua
Morris, Alison
Wu, Benjamin G.
Dawson, Rodney
Dheda, Keertan
Rom, William N.
Weiden, Michael D.
Venue: Cell Host & Microbe
Publisher: Elsevier BV
Published: 2017-04
Volume: 21
Issue: 4
Pages: 530-537.e4
ISSN: 1931-3128 (ISSN-L)
DOI: 10.1016/j.chom.2017.03.003
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 376 d)
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 › Surgery › 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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Anaerobic bacterial fermentation products increase tuberculosis risk in antiretroviral-drug-treated HIV patients.

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