Synbiotic HQP08 Supplementation for Hair Loss and Depressive Symptoms: An Open-Label Pilot Study of Clinical Outcomes and Gut Microbiome Changes.

Background: Gut microbiota dysregulation has been implicated in hair loss via the gut-skin axis, but human interventional data are limited. We previously showed that Bifidobacterium longum HK003 reverses alopecia-like phenotypes in mice. Methods: We conducted an open-label, single-arm pilot study to evaluate an HK003-containing synbiotic (HQP08) in 32 adults with self-reported hair loss over 8 weeks. The primary endpoint was the proportion of participants reporting improvement on the Patient Global Impression of Change (PGI-C) scale at week 8. Secondary outcomes included changes in hair loss severity, 60 s hair count, depressive symptoms (PHQ-9), safety, and gut microbiome composition (Chinese Clinical Trial Registry ChiCTR2500112698). Results: At week 8, 62.5% (20/32) of participants reported PGI-C improvement. Significant reductions were observed in hair loss severity (p = 0.0008), 60 s hair count (p = 0.0048), and PHQ-9 scores (p = 0.002). Younger age was associated with PGI-C response (OR per year 0.86, 95% CI: 0.73-0.98, p = 0.037). Metagenomic analysis identified engraftment of B. longum HK003-like profiles in a subset of participants at week 12. Changes in microbial pathways related to thiamine metabolism, vitamin B12 salvage, and lipopolysaccharide biosynthesis were associated with ΔPHQ-9 (FDR-adjusted p < 0.05), but not with hair-related endpoints. No serious adverse events occurred. Conclusions: This first-in-human pilot study suggests that HQP08 was well tolerated and was associated with within-participant changes in hair-loss measurements and PHQ-9 scores. Randomized controlled trials are warranted to confirm efficacy and further elucidate mechanisms within the gut-brain-skin axis.