Cell Host & Microbe
Volume 21, Issue 4, 12 April 2017, Pages 530-537.e4
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Short Article
Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients

https://doi.org/10.1016/j.chom.2017.03.003Get rights and content
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Highlights

  • Increased short-chain fatty acids (SCFAs) predict TB risk in HIV patients on ART

  • SCFAs block IFN-γ and IL-17A induced by M. tuberculosis antigens

  • SCFAs induce FoxP1 and correlate with TB antigen-induced pulmonary Tregs

  • SCFAs in the lower airways are associated with increased lung anaerobic bacteria

Summary

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.

Keywords

HIV
tuberculosis
lung
dysbiosis
short-chain fatty acids
FoxP3
FoxP1

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