Latent tuberculosis infection is associated with an enrichment of short chain fatty acid producing bacteria in the stool of women living with HIV

Abstract

<title>Abstract</title> <underline><bold>Background:</bold></underline> Latent tuberculosis infection (LTBI) is common in people living with HIV (PLHIV) in high TB burden settings. Active TB is associated with specific stool taxa; however, little is known about the stool microbiota and LTBI, including in PLHIV. <underline><bold>Method</bold></underline><bold>:</bold> Within a parent study that recruited adult females with HIV from Cape Town, South Africa into predefined age categories (18-25, 35-60 years), we characterised the stool microbiota of those with [interferon-<italic>γ</italic> release assay (IGRA)- and tuberculin skin test (TST)-positive] or without (IGRA- and TST-negative) LTBI (n=25 per group). 16S rRNA DNA sequences were analysed using QIIME2, Dirichlet Multinomial Mixtures, DESeq2 and PICRUSt2. <underline><bold>Results:</bold></underline><bold> </bold>No α- or β-diversity differences occurred by LTBI status; however, LTBI-positives were <italic>Faecalibacterium-, Blautia-, Gemmiger-, Bacteroides-</italic>enriched<italic> </italic>and <italic>Moryella-, Atopobium-, Corynebacterium-, Streptococcus</italic>-depleted. Inferred metagenome data showed LTBI-negative-enriched pathways included several involved in methylglyoxal degradation, L-arginine, putrescine, 4-aminobutanoate degradation and L-arginine and ornithine degradation. Stool from LTBI-positives demonstrated differential taxa abundance based on a quantitative response to antigen stimulation (<italic>Acidaminococcus-</italic>enrichment and <italic>Megamonas</italic>-, <italic>Alistipes</italic>-, and <italic>Paraprevotella</italic>-depletion associated with higher IGRA or TST responses, respectively). In LTBI-positives, older people had different β-diversities than younger people whereas, in LTBI-negatives, no differences occurred across age groups. <underline><bold>Conclusion:</bold></underline> Amongst female PLHIV, those with LTBI had, vs. those without LTBI, <italic>Faecalibacterium</italic>, <italic>Blautia</italic>, Gemmiger, <italic>Bacteriodes</italic>-enriched, which are producers of short chain fatty acids. Taxonomic differences amongst people with LTBI occurred according to quantitative response to antigen stimulation and age. These data enhance our understanding of the microbiome’s potential role in LTBI.