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There is limited knowledge on the effects of metformin in HF-induced intestinal irregularities in male and female rats with MetS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objectives<\/jats:title>\n                <jats:p>In this study, we investigated the sex-dependent effects of metformin treatment on the gut microbiota, intestinal Tight Junction (TJ) proteins, and inflammation parameters in HF-induced MetS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Fructose was given to the male and female rats as a 20% solution in drinking water for 15\u00a0weeks. Metformin (200\u00a0mg\/kg) was administered by gastric tube once a day during the final seven weeks. Biochemical, histopathological, immunohistochemical, and bioinformatics analyses were performed. Differences were considered statistically significant at <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The metformin treatment in fructose-fed rats promoted glucose, insulin, Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR), and Triglyceride (TG) values in both sexes. The inflammation score was significantly decreased with metformin treatment in fructose-fed male and female rats (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Moreover, metformin treatment significantly decreased Interleukin-1 Beta (IL-1\u03b2) and Tumor Necrosis Factor-Alpha (TNF-\u03b1) in ileum tissue from fructose-fed males (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Intestinal immunoreactivity of Occludin and Claudin-1 was increased with metformin treatment in fructose-fed female rats. HF and metformin treatment changed the gut microbial composition. <jats:italic>Firmicutes\/Bacteroidetes<\/jats:italic> (F\/B) ratio increased with HF in females. In the disease group, <jats:italic>Bifidobacterium pseudolongum<\/jats:italic>; in the treatment group, <jats:italic>Lactobacillus helveticus<\/jats:italic> and <jats:italic>Lactobacillus reuteri<\/jats:italic> are the prominent species in both sexes. When the male and female groups were compared, <jats:italic>Akkermansia muciniphila<\/jats:italic> was prominent in the male treatment group.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In conclusion, metformin treatment promoted biochemical parameters in both sexes of fructose-fed rats. Metformin showed a sex-dependent effect on inflammation parameters, permeability factors, and gut microbiota. Metformin has partly modulatory effects on fructose-induced intestinal changes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s40199-024-00521-2","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T08:01:52Z","timestamp":1718611312000},"page":"515-535","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigation of the relationship between inflammation and microbiota in the intestinal tissue of female and male rats fed with fructose: Modulatory role of metformin"],"prefix":"10.1007","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0923-2097","authenticated-orcid":false,"given":"Azimet","family":"Yal\u00e7\u0131n Bu\u011fdayc\u0131","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saadet \u00d6zen","family":"Akarca Dizakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00fcr\u015fide Ay\u015fe","family":"Demirel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suna","family":"\u00d6mero\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Akar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mecit Orhan","family":"Uluda\u011f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"issue":"2","key":"521_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11906-018-0812-z","volume":"20","author":"MG Saklayen","year":"2018","unstructured":"Saklayen MG. 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