{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:32:26Z","timestamp":1785162746107,"version":"3.55.0"},"reference-count":19,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biofermin Pharmaceutical Co., Ltd."}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>This randomized, parallel-group study aims to investigate the effects of the probiotic <jats:italic>Bifidobacterium bifidum<\/jats:italic> G9-1 (BBG9-1) on the symptoms of diarrhea or constipation in patients with type 2 diabetes mellitus (T2DM).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This study will examine 100 patients with T2DM who suffering from symptoms of diarrhea or constipation. Eligible patients will be randomly assigned 1:1 to two groups (group A, BBG9-1 group; group B, control group), after the baseline examination. Patients assigned to group A will receive probiotic BBG9-1 oral administration along with their current treatment for 12 weeks, and patients assigned to group B will continue the current treatment for 12 weeks without probiotic BBG9-1 oral administration. Subsequently, examinations similar to the baseline examinations will be performed. The primary endpoint will be a change in the Gastrointestinal Symptom Rating Scale (GSRS) total score from baseline to week 12. Secondary endpoints will include the following: change and percent change in parameters such as GSRS subdomain scores, fecal properties\/Bristol stool form scale, defecation frequency, biomarkers, gut microbiota, and macronutrients and factors that affect GSRS total score or constipation\/diarrhea subdomain scores from baseline to week 12.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>The results of this study will clarify the utility of probiotic BBG9-1 in the treatment of diarrhea or constipation in patients with T2DM.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/jrct.niph.go.jp\/en-latest-detail\/jRCTs051220127\" xlink:type=\"simple\">jRCTs051220127<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0295998","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T18:28:37Z","timestamp":1704997717000},"page":"e0295998","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Protocol of efficacy of bifidobacteria intake on gastrointestinal symptoms in symptomatic type 2 diabetes mellitus patients in abdominis: An open-label, randomized controlled trial (Binary STAR study)"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8794-0550","authenticated-orcid":true,"given":"Yoshitaka","family":"Hashimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genki","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Kitagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Hamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiaki","family":"Fukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"pone.0295998.ref001","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/S0140-6736(17)30058-2","article-title":"Type 2 diabetes","volume":"389","author":"S Chatterjee","year":"2017","journal-title":"Lancet"},{"key":"pone.0295998.ref002","doi-asserted-by":"crossref","first-page":"567","DOI":"10.17219\/acem\/67961","article-title":"Gastrointestinal complications in patients with diabetes mellitus","volume":"27","author":"AE Zawada","year":"2018","journal-title":"Adv Clin Exp Med"},{"key":"pone.0295998.ref003","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1001\/archinte.161.16.1989","article-title":"Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults","volume":"161","author":"P Bytzer","year":"2001","journal-title":"Arch Intern Med"},{"key":"pone.0295998.ref004","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s13300-016-0182-y","article-title":"A Practical Approach to Gastrointestinal Complications of Diabetes.","volume":"7","author":"A. 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