Tryptophan metabolomic profiling in persons with and without HIV

Abstract

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.

The authors' abstract, as published at the source. AIDS, 2026 · DOI ↗