Gut microbiome dysbiosis and alterations in kynurenine pathway of tryptophan metabolism are associated with depression in people with HIV

BACKGROUND: People with HIV have increased risk of depression and differed gut microbiome composition. While alterations in gut microbiome and kynurenine pathway of tryptophan metabolism have each been independently linked to depression in the general population, their interrelationships in people with HIV remain unclear. METHODS: People with HIV with available gut microbiome data and depression assessments were included (n = 365). We assessed the associations between gut microbiome, evidence of depression, kynurenine metabolites, inflammatory markers, clinical variables. RESULTS: Individuals with evidence of depression (n = 32) had significantly higher plasma levels of IL-6 and quinolinic acid, along with altered gut microbiome composition (dysbiosis), compared to individuals without evidence of depression (n = 333). No statistically significant correlation was found between depression-related gut microbial dysbiosis and levels of kynurenine metabolites or inflammatory markers, whereas the latter two correlated with each other. Mediation analysis further showed a borderline but not statistically significant indirect effect of kynurenine and quinolinic acid levels on depression through inflammatory marker IL-6. CONCLUSIONS: Our data show that gut microbiome dysbiosis is associated with depression in people with HIV, but not with the altered kynurenine metabolites linked to depression. These findings suggest distinct pathways linking gut microbiome dysbiosis and alterations in kynurenine pathway of tryptophan metabolism to depression.