Landscapes of gut microbiome and metabolic signatures in vitiligo patients with co-morbid emotional distress

Background: Vitiligo is a depigmentation disorder frequently associated with emotional distress; however, the precise mechanisms underlying this co-morbidity remain unclear. Objective: This study aims to investigate whether gut dysbiosis and gut metabolites contributes to emotional distress in patients with vitiligo. Methods: Depression and anxiety were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Totally enrolled 28 vitiligo patients were diagnosed with depression or anxiety (VWD), 44 without such conditions (VTD), and 37 healthy controls (HC). Stool samples were analyzed using 16S rRNA gene sequencing and liquid chromatography triple quadrupole tandem mass spectrometry. Results: The intestinal flora of VWD group changed significantly with reduced α-diversity. The β-diversity varied among groups. Megasphaera and Anaerostipes increased in the VWD group, whereas Bilophila etc. decreased. Linear Discriminant Analysis Effect Size revealed Lachnoclostridium as a representative flora in the VWD and Faecalibacterium as a representative flora in the VTD. Metabolites such as L-glutamic acid and indole were lower in the VWD group than in the HC, while oleamide, cuminaldehyde, and taurine were higher in the VWD with VTD group. Lachnoclostridium negatively correlated with indole and L-glutamic acid. This study identified notable variations in pathways involved in the biosynthesis of phenylalanine, tyrosine, and tryptophan bile secretion, GABAergic synapses, and taurine and hypotaurine metabolism between the VWD and HC groups. Conclusion: Specific fecal microbes and metabolites may contribute to the pathogenesis of VWD. These findings provide a novel perspective for addressing emotional distress in patients with vitiligo by targeting the gut-brain-skin axis.