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[Preprint]. 2024 Apr 27:2024.04.26.24306431.
doi: 10.1101/2024.04.26.24306431.

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

Georgina Nyawo, Charissa Naidoo, Benjamin G Wu, Benjamin Kwok, Jose C Clemente, Yonghua Li, Stephanie Minnies, Byron Reeve, Suventha Moodley, Thadathilankal-Jess John, Sumanth Karamchand, Shivani Singh, Alfonso Pecararo, Anton Doubell, Charles Kyriakakis, Robin Warren, Leopoldo N Segal, Grant Theron

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

Georgina Nyawo et al. medRxiv. .

Update in

Abstract

Background: The 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.

Methods: People 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.

Results: PF from people with definite (dTB, n=91), probable (pTB, n=25), and non- (nTB, n=23) tuberculous pericarditis differed in β-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. β-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.

Conclusions: PF 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.

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