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

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

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

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.

Original languageEnglish
Pages (from-to)530-537.e4
JournalCell Host and Microbe
Volume21
Issue number4
DOIs
StatePublished - 12 Apr 2017

Keywords

  • FoxP1
  • FoxP3
  • HIV
  • dysbiosis
  • lung
  • short-chain fatty acids
  • tuberculosis

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