Tryptophan metabolomic profiling in persons with and without HIV

Background: 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. Methods: 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. Results: 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. Conclusions: 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.