{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:05:05Z","timestamp":1790067905532,"version":"4.0.1"},"reference-count":42,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"InnoHK initiative of the Innovation and Technology Commission of the Hong Kong Special Administrative Region Government","id":[{"id":"https:\/\/ror.org\/04vf9tr09","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Gut microbiota dysregulation has been implicated in hair loss via the gut\u2013skin 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\u20130.98, 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 \u0394PHQ-9 (FDR-adjusted p &lt; 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\u2013brain\u2013skin axis.<\/jats:p>","DOI":"10.3390\/nu18193111","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:17:54Z","timestamp":1790065074000},"page":"3111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synbiotic HQP08 Supplementation for Hair Loss and Depressive Symptoms: An Open-Label Pilot Study of Clinical Outcomes and Gut Microbiome Changes"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5552-7534","authenticated-orcid":false,"given":"Zhilu","family":"Xu","sequence":"first","affiliation":[{"name":"Microbiota I-Center (MagIC), Hong Kong SAR, China"},{"name":"Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Raphaela I.","family":"Lau","sequence":"additional","affiliation":[{"name":"Microbiota I-Center (MagIC), Hong Kong SAR, China"},{"name":"Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Haoyu","family":"Qi","sequence":"additional","affiliation":[{"name":"Microbiota I-Center (MagIC), Hong Kong SAR, China"},{"name":"Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7706-9370","authenticated-orcid":false,"given":"Martin C. S.","family":"Wong","sequence":"additional","affiliation":[{"name":"Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Kingsley H. N.","family":"Chan","sequence":"additional","affiliation":[{"name":"Dermamier Skin and Laser Center, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4967-9985","authenticated-orcid":false,"given":"Ivan S. F.","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Jessica Y. L.","family":"Ching","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Pui Kuan","family":"Cheong","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7388-2436","authenticated-orcid":false,"given":"Francis K. L.","family":"Chan","sequence":"additional","affiliation":[{"name":"Microbiota I-Center (MagIC), Hong Kong SAR, China"},{"name":"Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Siew C.","family":"Ng","sequence":"additional","affiliation":[{"name":"Microbiota I-Center (MagIC), Hong Kong SAR, China"},{"name":"Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2473524","DOI":"10.1080\/19490976.2025.2473524","article-title":"The gut-skin axis: A bi-directional, microbiota-driven relationship with therapeutic potential","volume":"17","author":"Celiberto","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1111\/jdv.18926","article-title":"The burden of alopecia areata: A scoping review focusing on quality of life, mental health and work productivity","volume":"37","author":"Muntyanu","year":"2023","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1001\/jamadermatol.2021.5743","article-title":"Relative Efficacy of Minoxidil and the 5-\u03b1 Reductase Inhibitors in Androgenetic Alopecia Treatment of Male Patients: A Network Meta-analysis","volume":"158","author":"Gupta","year":"2022","journal-title":"JAMA Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jaad.2020.06.1009","article-title":"Oral minoxidil treatment for hair loss: A review of efficacy and safety","volume":"84","author":"Randolph","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1056\/NEJMoa2110343","article-title":"Two Phase 3 Trials of Baricitinib for Alopecia Areata","volume":"386","author":"King","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/S0140-6736(23)00222-2","article-title":"Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: A randomised, double-blind, multicentre, phase 2b\u20133 trial","volume":"401","author":"King","year":"2023","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100363","DOI":"10.1016\/j.xjidi.2025.100363","article-title":"Cutaneous and Gut Dysbiosis in Alopecia Areata: A Review","volume":"5","author":"Burma","year":"2025","journal-title":"JID Innov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1056\/NEJM199908123410706","article-title":"The biology of hair follicles","volume":"341","author":"Paus","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nm.3645","article-title":"Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition","volume":"20","author":"Xing","year":"2014","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.14309\/crj.2017.107","article-title":"Hair Growth in Two Alopecia Patients after Fecal Microbiota Transplant","volume":"4","author":"Rebello","year":"2017","journal-title":"ACG Case Rep. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1136\/gutjnl-2021-326320","article-title":"Modulation of gut microbiota impacts diet-induced and drug-induced alopecia in mice","volume":"71","author":"Lam","year":"2022","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S1473-3099(23)00685-0","article-title":"A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): A randomised, double-blind, placebo-controlled trial","volume":"24","author":"Lau","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/bioinformatics\/bty648","article-title":"Scaling read aligners to hundreds of threads on general-purpose processors","volume":"35","author":"Langmead","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","article-title":"Ultrafast and memory-efficient alignment of short DNA sequences to the human genome","volume":"10","author":"Langmead","year":"2009","journal-title":"Genome Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1038\/s41587-023-01688-w","article-title":"Extending and improving metagenomic taxonomic profiling with uncharacterized species using MetaPhlAn 4","volume":"41","author":"Beghini","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e65088","DOI":"10.7554\/eLife.65088","article-title":"Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3","volume":"10","author":"Beghini","year":"2021","journal-title":"eLife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1101\/gr.216242.116","article-title":"Microbial strain-level population structure and genetic diversity from metagenomes","volume":"27","author":"Truong","year":"2017","journal-title":"Genome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.21105\/joss.02017","article-title":"ggalluvial: Layered Grammar for Alluvial Plots","volume":"5","author":"Brunson","year":"2020","journal-title":"J. Open Source Softw."},{"key":"ref_21","unstructured":"R Core Team (2026). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/bioinformatics\/bty633","article-title":"ape 5.0: An environment for modern phylogenetics and evolutionary analyses in R","volume":"35","author":"Paradis","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1093\/bioinformatics\/btq706","article-title":"phangorn: Phylogenetic analysis in R","volume":"27","author":"Schliep","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_24","unstructured":"Oksanen, J., Simpson, G., Blanchet, F.G., Kindt, R., Legendre, P., Minchin, P., Hara, R., Solymos, P., Stevens, H., and Sz\u00f6cs, E. (Vegan Community Ecology Package, 2022). Vegan Community Ecology Package, Version 2.6."},{"key":"ref_25","first-page":"1","article-title":"ggplot2: Elegant Graphics for Data Analysis","volume":"35","year":"2010","journal-title":"J. Stat. Softw. Book Rev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fu, H., Xu, T., Zhao, W., Jiang, L., and Shan, S. (2024). Roles of gut microbiota in androgenetic alopecia: Insights from Mendelian randomization analysis. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1360445"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/ame2.12414","article-title":"Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma (PRP)","volume":"7","author":"Zhang","year":"2024","journal-title":"Anim. Model. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"De Pessemier, B., Grine, L., Debaere, M., Maes, A., Paetzold, B., and Callewaert, C. (2021). Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions. Microorganisms, 9.","DOI":"10.3390\/microorganisms9020353"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nrgastro.2014.66","article-title":"The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic","volume":"11","author":"Hill","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41575-020-0344-2","article-title":"The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics","volume":"17","author":"Swanson","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.cell.2018.08.041","article-title":"Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features","volume":"174","author":"Zmora","year":"2018","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.chom.2016.09.001","article-title":"Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on Individualized Features of the Resident Microbiome","volume":"20","author":"Bottacini","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-018-0092-4","article-title":"An exclusive metabolic niche enables strain engraftment in the gut microbiota","volume":"557","author":"Shepherd","year":"2018","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.chom.2019.03.007","article-title":"Adaptive Evolution Within Gut Microbiomes of Healthy People","volume":"25","author":"Zhao","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e0018423","DOI":"10.1128\/mmbr.00184-23","article-title":"Vitamin biosynthesis in the gut: Interplay between mammalian host and its resident microbiota","volume":"89","author":"Tarracchini","year":"2025","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kennedy, D.O. (2016). B Vitamins and the Brain: Mechanisms, Dose and Efficacy\u2014A Review. Nutrients, 8.","DOI":"10.3390\/nu8020068"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100790","DOI":"10.1016\/j.bbih.2024.100790","article-title":"Vitamin-mediated interaction between the gut microbiome and mitochondria in depression: A systematic review-based integrated perspective","volume":"38","author":"Bisle","year":"2024","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1159\/000485080","article-title":"Immune Privilege Collapse and Alopecia Development: Is Stress a Factor","volume":"4","author":"Azzawi","year":"2018","journal-title":"Ski. Appendage Disord."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Shafiei-Jahani, P., Li, X., Akbari, A., Haniff, E., Ziprick, M., Carlisle, R., Goh, C., Holland, V., and Akbari, O. (2026). Hair follicle immune privilege in autoimmune and immune-mediated alopecias: Paths toward reestablishing immune tolerance. Front Med., 13.","DOI":"10.3389\/fmed.2026.1805170"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/j.1365-2982.2011.01796.x","article-title":"The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication","volume":"23","author":"Bercik","year":"2011","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1053\/j.gastro.2017.05.003","article-title":"Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients with Irritable Bowel Syndrome","volume":"153","author":"Hall","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.bbi.2024.12.028","article-title":"Bifidobacterium longum CECT 30763 improves depressive- and anxiety-like behavior in a social defeat mouse model through the immune and dopaminergic systems","volume":"125","author":"Tamayo","year":"2025","journal-title":"Brain Behav. Immun."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3111\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:33:12Z","timestamp":1790065992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":42,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["nu18193111"],"URL":"https:\/\/doi.org\/10.3390\/nu18193111","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]}}}