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This study tested the hypothesis that a leucine-rich diet could attenuate inflammation and improve gut health in a mouse model of IBD. Specifically, we investigated the effects of a leucine-rich diet on dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) SAMP1\/YitFC (SAMP) mice colonized with human gut microbiota (hGF-SAMP). hGF-SAMP mice were fed one of four different diets: standard mouse diet (CHOW), American diet (AD), leucine-rich AD (AD + AA), or leucine-rich CHOW diet (CH + AA). Body weight, myeloperoxidase (MPO) activity, gut permeability, colonoscopy scores, and histological analysis were measured. Mice on a leucine-rich CHOW diet showed a decrease in fecal MPO prior to DSS treatment as compared to those on a regular diet (p &gt; 0.05); however, after week five, prior to DSS, this effect had diminished. Following DSS treatment, there was no significant difference in gut permeability, fecal MPO activity, or body weight changes between the leucine-supplemented and control groups. These findings suggest that while a leucine-rich diet may transiently affect fecal MPO levels in hGF-SAMP mice, it does not confer protection against DSS-induced colitis symptoms or mitigate inflammation in the long term.<\/jats:p>","DOI":"10.3390\/ijms252111748","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T04:59:54Z","timestamp":1730437194000},"page":"11748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Leucine-Enriched Diet Reduces Fecal MPO but Does Not Protect Against DSS Colitis in a Mouse Model of Crohn\u2019s Disease-like Ileitis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0179-2057","authenticated-orcid":false,"given":"Drishtant","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Division of Gastroenterology & Liver Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8779-088X","authenticated-orcid":false,"given":"Paola","family":"Menghini","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Liver Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0713-5605","authenticated-orcid":false,"given":"Alexander","family":"Rodriguez-Palacios","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Liver Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"},{"name":"Mouse Models Core, Silvio O\u2019Conte Cleveland Digestive Diseases Research Core Center, Cleveland, OH 44106, USA"},{"name":"Germ-Free and Gut Microbiome Core, Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca Di","family":"Martino","sequence":"additional","affiliation":[{"name":"Case Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Cominelli","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Liver Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"},{"name":"Mouse Models Core, Silvio O\u2019Conte Cleveland Digestive Diseases Research Core Center, Cleveland, OH 44106, USA"},{"name":"Germ-Free and Gut Microbiome Core, Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8369-919X","authenticated-orcid":false,"given":"Abigail Raffner","family":"Basson","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Division of Gastroenterology & Liver Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.aninu.2020.11.003","article-title":"Mutual interaction between gut microbiota and pro-tein\/amino acid metabolism for host mucosal immunity and health","volume":"7","author":"Wu","year":"2021","journal-title":"Anim Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1136\/gutjnl-2020-323071","article-title":"Gut microbiota-derived metabolites as central regulators in metabolic disorders","volume":"70","author":"Agus","year":"2020","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Aldars-Garcia, L., Gisbert, J.P., and Chaparro, M. 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