Characterising the urinary acylcarnitine and amino acid profiles of patients with HIV/TB co-infection, using LC-MS metabolomics

Abstract

This study comprises a comprehensive investigation of the urinary acylcarnitine and amino acid profiles in patients with HIV, TB, and HIV/TB co-infection using LC-MS metabolomics. It addresses a critical gap in current research by exploring the metabolic interplay in HIV/TB co-infection, a domain less extensively studied compared to the individual effects of HIV and Mtb infection. Recognising the potential of metabolomics in enhancing our understanding of HIV/TB co-infection and its immunological impact on host metabolism, this research aimed to characterise the urinary metabolome of individuals afflicted by these conditions. Such insights are pivotal for developing novel treatments and diagnostic strategies to effectively manage the HIV/TB syndemic. In this pursuit, urine samples from 9 HIV/TB co-infected, 7 HIV-only, and 41 TB-only patients, along with 32 healthy controls, were analysed. The analysis employed three targeted HPLC-MS/MS methods, allowing for the distinct assessment of urinary amino acids using the ChromSystems MassChrom® Amino Acid Analysis kit, as well as acylcarnitines and the tryptophan derivative 5-hydroxyindoleacetic acid (5-HIAA) through newly established and validated methods. The validation of these methods encompassed a thorough evaluation of selectivity, linearity, precision, and accuracy, ensuring the reliability of the findings. The results revealed significant alterations in the amino acid metabolome across all infected cohorts. Notably, there was a marked decrease in tryptophan and glycine levels, coupled with increased saccharopine and hydroxykynurenine levels. Enhanced lysine degradation via the saccharopine pathway was evident in HIV/TB co-infected and TB-only patients, as indicated by a significantly increased saccharopine/lysine ratio. While amino acid levels predominantly decreased in the HIV-only patients, an increase was observed in those with TB-only compared to healthy controls. The co-infected cohort did not exhibit a clear trend, suggesting a complex interplay of metabolic processes in the co-infection state. Although changes in acylcarnitines and 5-HIAA were not statistically significant, there were indications of generally elevated medium-chain acylcarnitines in the TB-only and HIV/TB co-infected cohorts. These findings point towards an altered net protein turnover, inflammation, lipid and amino acid catabolism, and potentially diabetic-like hyperglycaemia in the HIV/TB co-infected state, predominantly driven by Mtb infection. Furthermore, this study lays the groundwork for future research aiming to identify robust disease markers, as it suggests that the effects of HIV and Mtb infection on the amino acid metabolome are attenuated in the co-infected state. Overall, this study not only contributes to a deeper understanding of the metabolic complexities associated with HIV, TB, and their co-infection but also opens new avenues for targeted therapeutic interventions in managing these challenging infectious diseases.