{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:53:01Z","timestamp":1789685581664,"version":"4.0.1"},"reference-count":36,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Respiratory symptoms are prevalent in the general population, and they are associated with a decline in lung function and increased mortality. The gut\u2013lung connection suggests intestinal dysbiosis may impact lung diseases, with Akkermansia muciniphila showing promise in regulating extraintestinal diseases. However, its application in patients with respiratory symptoms lacks clinical trial evidence. In this randomized, double-blind trial, ETB-F01, containing heat-killed A. muciniphila strain EB-AMDK19, was compared with a placebo in patients experiencing respiratory symptoms for 4 to 12 weeks. The primary outcome was improvement in Breathlessness, Cough, and Sputum Scale (BCSS) score over 12 weeks. Secondary outcomes included lung function, fractional exhaled nitric oxide (FeNO), modified Medical Research Council (mMRC) dyspnea scale, St. George\u2019s Respiratory Questionnaire (SGRQ), and Visual Analog Scale (VAS) score. The primary analysis was performed in the per-protocol set, with a sensitivity analysis in the full analysis set. In the per-protocol population, 68 participants were randomly assigned to the ETB-F01 group and 65 to the placebo group. ETB-F01 had a superior efficacy over placebo in improving BCSS total scores (between-group difference = \u22120.8 (95% confidence interval, \u22121.4\u2013\u22120.3), p-value = 0.004). Specifically, there was a significant reduction in BCSS breathlessness and cough domain scores with ETB-F01. While trends toward improvement in lung function were noted, statistical significance was not achieved. No significant differences were observed in FeNO and other symptom scores (mMRC, SGRQ, and VAS). In safety profile, ETB-F01 did not cause any serious adverse events. These results suggest that ETB-F01 is safe and effective for alleviating respiratory symptoms.<\/jats:p>","DOI":"10.3390\/nu16234113","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T07:28:01Z","timestamp":1732778881000},"page":"4113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy of ETB-F01, Heat-Killed Akkermansia muciniphila Strain EB-AMDK19, in Patients with Respiratory Symptoms: A Multicenter Clinical Trial"],"prefix":"10.3390","volume":"16","author":[{"given":"Hyun Woo","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Respiratory and Critical Care, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, College of Medicine, Seoul National University, Seoul 07061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Nam","family":"Lee","sequence":"additional","affiliation":[{"name":"Enterobiome Inc., Goyang-si 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Gu","family":"Seo","sequence":"additional","affiliation":[{"name":"Enterobiome Inc., Goyang-si 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yemo","family":"Koo","sequence":"additional","affiliation":[{"name":"Enterobiome Inc., Goyang-si 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Yoon","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2536-6151","authenticated-orcid":false,"given":"Cheon Woong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Respiratory, Allergy and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong 14353, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suh-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Hospital, Seoul 07061, Republic of Korea"},{"name":"Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 07061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Ryeol","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Yongin Severance Hospital, College of Medicine, Yonsei University, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo-Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8387-4907","authenticated-orcid":false,"given":"Hye Sook","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Hospital, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"00067","DOI":"10.1183\/23120541.00067-2022","article-title":"Respiratory symptoms and their determinants in the general Spanish population: Changes over 20 years","volume":"8","author":"Miravitlles","year":"2022","journal-title":"ERJ Open Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/j.1752-699X.2009.00172.x","article-title":"Cold-related respiratory symptoms in the general population","volume":"4","author":"Harju","year":"2010","journal-title":"Clin. 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