Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients

Publication date: Available online 30 March 2017
Source:Cell Host & Microbe
Author(s): Leopoldo N. Segal, Jose C. Clemente, Yonghua Li, Chunhai Ruan, Jane Cao, Mauricio Danckers, Alison Morris, Sarah Tapyrik, Benjamin G. Wu, Philip Diaz, Gregory Calligaro, Rodney Dawson, Richard N. van Zyl-Smit, Keertan Dheda, William N. Rom, Michael D. Weiden
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.

Graphical abstract

Teaser

HIV patients on antiretroviral therapy (ART) are vulnerable to tuberculosis. Segal et al. show that short-chain fatty acids (SCFAs) produced by the increased abundance of lung anaerobic bacteria in these patients inhibit the immune response to M. tuberculosis, likely enhancing tuberculosis susceptibility.


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