The effect of sex and HIV on the TB-induced altered sputum metabolome

Abstract

Various studies have identified TB-induced metabolome variations. However, in most of these studies, the unaccounted-for variation between individual patients is noteworthy. To investigate one potential cause of this variation, we evaluated the effect of sex on the sputum metabolomes of TB and TB/HIV co-infected individuals. Untargeted GCxGC/TOF-MS analyses were applied to the sputum of 31 TB+ and 197 TB- individuals. Univariate statistical methods were used to identify metabolites that differ significantly between TB+ and TB- individuals within each sex (male and female) 1) irrespective of HIV status and 2) for HIV+ patients. Ignoring HIV status, 21 compounds were significantly different between the TB+ and TB- individuals within the female subgroup (11% lipids; 10% carbohydrates; 1% amino acids, 5% other and 73% unannotated), and six within the male subgroup (20% lipids; 40% carbohydrates; 6% amino acids, 7% other and 27% unannotated). For the HIV+ patients (TB+ vs TB-), a total of 125 compounds were significant within the female subgroup (16% lipids; 8% carbohydrates; 12% amino acids, 6% organic acids, 8% other and 50% unannotated), and 44 within the male subgroup (17% lipids; 2% carbohydrates; 14% amino acids related, 8% organic acids, 9% other and 50% unannotated). One annotated compound, 1-oleoyl lysophosphatidic acid, was consistently identified as a TB marker, irrespective of sex or HIV status. In this cohort, sex played a definite role in how TB and TB/HIV infection perturbs the metabolome. Our findings, therefore, highlight the need for better stratified cohorts in metabolomics studies.