{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:14:17Z","timestamp":1788444857112,"version":"build-2803163510"},"reference-count":35,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"unspecified","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"B-Crobes Laboratory Sdn. Bhd","award":["888\/UN6.INJABAR\/HK.07.01\/2024"],"award-info":[{"award-number":["888\/UN6.INJABAR\/HK.07.01\/2024"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,5,12]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Acne vulgaris is a chronic inflammatory condition primarily caused by\n                      <jats:italic>Cutibacterium acnes<\/jats:italic>\n                      , which disrupts skin homeostasis, thereby triggering immune responses and sebum metabolism. Dysbiosis is an imbalance in the skin and gut microbiota identified as a significant factor contributing to acne progression. Standard therapy often relies on antibiotics, but the long-term use has increased antibiotic resistance, including in Indonesia. Consequently, alternative methods, such as probiotics and mesenchymal stromal cell secretomes, are gaining attention for immunomodulatory and regenerative properties. These novel therapies have shown promising results in modulating the skin and gut microbiota while reducing inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>A phase 2 double-blind randomised controlled trial will be conducted using a parallel group design with four arms, namely: (1) standard therapy with oral probiotics and topical secretome (placebo), (2) standard therapy with oral probiotics (placebo) and topical secretome, (3) standard therapy with oral probiotics and topical secretome and (4) standard therapy with oral probiotics (placebo) and topical secretome (placebo). Sixty-four patients with mild to moderate acne vulgaris will be randomly allocated to these groups. Interventions will be administered over a period of 8 weeks, with outcomes to be measured at baseline and post-therapy. This study will be conducted at the Dermatology and Venereology Department of Bali Mandara General Hospital (RSBM). The primary outcome will be the reduction of comedones and inflammatory lesions, assessed using the Yolov8 method. Secondary outcomes will include gut and skin health parameters, such as tryptophan metabolites, collagen, pH, moisture, sebum levels and IL-6, to explore the relationship between microbiome balance, skin condition and inflammation in acne.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study will be conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and the International Conference on Harmonisation\u2013Good Clinical Practice guidelines. Ethical approval has been granted by the Health Research Ethics Committee of Bali Mandara Regional Hospital (Approval Reference Number: 060\/EA\/KEPK.RSBM.DINKES\/2024). All participants will provide written informed consent prior to enrolment. Data confidentiality and participant safety will be upheld throughout the trial. The results of this study will be disseminated through journals, scientific conferences and relevant academic platforms to ensure wide accessibility and to support further research and clinical application in the field of dermatology, particularly in addressing antibiotic resistance and microbiome-based acne therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial results\" xlink:href=\"NCT06925386\">NCT06925386<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-109586","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:35:29Z","timestamp":1780590929000},"page":"e109586","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Oral probiotics and topical secretome to enhance clinical outcomes and microbiome restoration in acne vulgaris: a double-blind, randomised controlled trial protocol"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct06925386","registry":"10.18810\/clinical-trials-gov","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2099-1062","authenticated-orcid":false,"given":"Keri","family":"Lestari","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia"},{"name":"Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Sumedang, West Java, Indonesia"},{"name":"Medication Therapy Adherence Clinic (MTAC), Universitas Padjadjaran, Bandung, West java, Indonesia"},{"name":"West Java Research Centre, Universitas Padjadjaran, Bandung, West Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida Ayu Manik Partha","family":"Sutema","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia"},{"name":"Clinical Pharmacy Study Program, Bali International University, Denpasar, Bali, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma Rahayu","family":"Latarissa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia"},{"name":"Medication Therapy Adherence Clinic (MTAC), Universitas Padjadjaran, Bandung, West java, Indonesia"},{"name":"West Java Research Centre, Universitas Padjadjaran, Bandung, West Java, Indonesia"},{"name":"Department of Medical Affairs, B-Crobes Laboratory, Ipoh, Perak, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok Fang","family":"Oon","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, B-Crobes Laboratory, Ipoh, Perak, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norain Mohd","family":"Tamsir","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, B-Crobes Laboratory, Ipoh, Perak, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Noor","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, B-Crobes Laboratory, Ipoh, Perak, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I Gusti Ayu Rai","family":"Widowati","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Study Program, Bali International University, Denpasar, Bali, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia Retna","family":"Sartika","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia"},{"name":"PT Prodia StemCell Indonesia, Central Jakarta, Jakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni Wayan Eka","family":"Ciptasari","sequence":"additional","affiliation":[{"name":"Ngoerah Sun Wellness and Aesthetic Center, Prof. Dr. I.G.N.G. 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