Bad company? The pericardium microbiome in people investigated for tuberculosis pericarditis in an HIV-prevalent setting

BackgroundThe microbiome likely plays a role in tuberculosis (TB) pathogenesis. We evaluated the site-of-disease microbiome and predicted metagenome in people with presumptive tuberculous pericarditis, a major cause of mortality, and explored for the first time, the interaction between its association with C-reactive protein (CRP), a potential diagnostic biomarker and the site-of-disease microbiome in extrapulmonary TB. MethodsPeople with effusions requiring diagnostic pericardiocentesis (n=139) provided background sampling controls and pericardial fluid (PF) for 16S rRNA gene sequencing analysed using QIIME2 and PICRUSt2. Blood was collected to measure CRP. ResultsPF from people with definite (dTB, n=91), probable (pTB, n=25), and non- (nTB, n=23) tuberculous pericarditis differed in {beta}-diversity. dTBs were, vs. nTBs, Mycobacterium-, Lacticigenium-, and Kocuria-enriched. Within dTBs, HIV-positives were Mycobacterium-, Bifidobacterium-, Methylobacterium-, and Leptothrix-enriched vs. HIV-negatives and HIV-positive dTBs on ART were Mycobacterium- and Bifidobacterium-depleted vs. those not on ART. Compared to nTBs, dTBs exhibited short-chain fatty acid (SCFA) and mycobacterial metabolism microbial pathway enrichment. People with additional non-pericardial involvement had differentially PF taxa (e.g., Mycobacterium-enrichment and Streptococcus-depletion associated with pulmonary infiltrates). Mycobacterium reads were in 34% (31/91), 8% (2/25) and 17% (4/23) of dTBs, pTBs, and nTBs, respectively. {beta}-diversity differed between patients with CRP above vs. below the median value (Pseudomonas-depleted). There was no correlation between enriched taxa in dTBs and CRP. ConclusionsPF is compositionally distinct based on TB status, HIV (and ART) status and dTBs are enriched in SCFA-associated taxa. The clinical significance of these findings, including mycobacterial reads in nTBs and pTBs, requires evaluation.