Tryptophan metabolomic profiling in persons with and without HIV

Full tryptophan (T) profiling allows determination of T-metabolites from the serotonin, kynurenine (K) and gut-integrity/indole pathways. We assessed T-metabolites, depressive symptoms, cognitive function and sleep measures in persons with and without HIV.

Persons with HIV on ART and lifestyle-similar persons without HIV completed depressive symptoms questionnaire (PHQ-9), cognitive testing (T-score), actigraphy sleep measures and early morning fasting blood sampling for metabolomic profiling (LC-MS, UK National Phenome Centre). Statistical analysis used Mann-Whitney U tests and Spearman rank correlation.

Of 468 individuals (345 with HIV), 81% were male individuals and median age was 58 (IQR 53-63) years. Several metabolites, including K, K/T ratio, citrulline and 5-hydroxyindole-acetic-acid, differed in those with and without HIV. Median (IQR) PHQ-9 scores were 5 (1-10) and 1 (0-3) in those with and without HIV, respectively. In those with HIV, higher PHQ-9 scores were associated with higher K-pathway markers [quinolinic acid (P = 0.05), K (P = 0.02) and K/T ratio (P = 0.02)] but associations were generally weaker in those without HIV. Cognitive testing T-score [with HIV: 50 (44-54.9); without HIV: 52 (48.3-55.8)] was positively associated with higher gut-integrity/indole-markers in those with HIV [citrulline (P < 0.0001), indole-3-acetic-acid (P < 0.0001)], but less so in those without HIV. No associations between any actigraphy sleep measures and T-metabolites were observed.

K-pathway metabolites (driven by peripheral inflammatory responses) are associated with depressive symptoms and metabolites of gut health associated with cognitive function in those with HIV; these observations were less evident in those without HIV. Further understanding of these mechanisms could assist the development of future therapeutic interventions.