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Prot."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The probiotic mixture Prohep has been studied as a potential therapy for liver diseases such as MASLD, MASH, and HCC. To evaluate its safety, we conducted an experiment on CD-1 mice to assess its acute, subacute, and subchronic oral toxicity. The results showed that Prohep intake did not cause any morbidity or mortality, nor did it produce adverse changes in body weight, histopathological, haematological, or biochemical parameters. Therefore, Prohep is considered safe for consumption, with LD\n                    <jats:sub>50<\/jats:sub>\n                    of Prohep being higher than 5000\u00a0mg\/kg (category 5, LD\n                    <jats:sub>50<\/jats:sub>\n                    \u2009&gt;\u20092000\u00a0mg\/kg) and no-observed-adverse-effect-level (NOAEL) of Prohep being 2800\u00a0mg\/kg. Furthermore, we investigated the ability of Prohep to modulate gut microbiota under both normal chow and high-fat diets. Based on faecal DNA sequencing results, a continuous 28-day course of Prohep supplementation is required to achieve complete reshaping of the gut microbiota composition. This 28-day supplementation window may therefore be informative for designing human dosing regimens aimed at inducing durable, clinically meaningful modulation of the gut microbiota. The modulatory effects of Prohep supplementation on gut microbiota were still observed 28 days after withdrawal. These findings provide valuable information for the pharmaceutical use of Prohep, including its safety and optimal duration of probiotic supplementation.\n                  <\/jats:p>","DOI":"10.1007\/s12602-026-11209-1","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:20:59Z","timestamp":1789114859000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety Assessment on Probiotic Mixture \u201cProhep\u201d and Longitudinal Evaluation on its Gut Microbial Modulation Ability in Mice"],"prefix":"10.1007","author":[{"given":"Fangfei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koei Ho Lam","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9258-0716","authenticated-orcid":false,"given":"Emily Kwun Kwan","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congjia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8175-7069","authenticated-orcid":false,"given":"Jetty Chung-Yung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1252-5667","authenticated-orcid":false,"family":"Felicianna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsena Jasiel","family":"Ismaiah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoi Kit Matthew","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-4346","authenticated-orcid":false,"given":"Hani","family":"El-Nezami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"11209_CR1","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.3389\/fimmu.2020.02192","volume":"11","author":"E Stavropoulou","year":"2020","unstructured":"Stavropoulou E, Bezirtzoglou E (2020) Probiotics in Medicine: A Long Debate. 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