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This study evaluated the effect of two coffee by-products, coffee pulp (CP) and coffee silverskin (SK), on fructose-induced intestinal changes. Sprague\u2013Dawley rats were assigned to six groups (n = 6\/group) for 10 weeks: Control, Fructose (FRU; 20% fructose in drinking water), CP, CP + FRU, SK, and SK + FRU. CP and SK were administered by oral gavage (250 mg\/kg\/day) using corn oil as vehicle. Intestinal morphology, gene expression (RT-qPCR), and gut microbiota composition (16S rRNA sequencing) were assessed. Fructose significantly increased jejunal expression of the glucose transporters SGLT1 and GLUT2. CP and SK reversed SGLT1 and GLUT2 overexpression and reduced GLUT5 expression relative to the FRU group. Fructose also markedly increased expression of sweet taste receptors TAS1R2 and TAS1R3 and the transcription factors SREBP-1c and ChREBP. Both CP and SK normalized TAS1R2 and TAS1R3 expression, whereas SK additionally prevented SREBP-1c and ChREBP overexpression. Both by-products restored fructose-induced reductions in microbial richness and alpha diversity. CP also modified beta diversity and increased the abundance of the genus Blautia compared with FRU. In conclusion, CP and SK reversed several fructose-induced intestinal alterations, namely in the jejunal expression of sugar-sensing and absorption-related genes. Additionally, CP showed microbiota-modulating effects, whereas SK modulated the jejunal expression of key transcription factors (SREBP-1c and ChREBP) involved in carbohydrate and lipid metabolism. Overall, these findings suggest that CP and SK may represent promising candidates for mitigating fructose-induced intestinal alterations.<\/jats:p>","DOI":"10.3390\/biom16071069","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:48:28Z","timestamp":1784717308000},"page":"1069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Coffee Pulp and Silverskin Mitigate Fructose-Induced Intestinal Alterations in Rats"],"prefix":"10.3390","volume":"16","author":[{"given":"Francisca","family":"Silva","sequence":"first","affiliation":[{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal"},{"name":"Nutrition & Metabolism, Comprehensive Health Research Centre (CHRC), NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2600-8599","authenticated-orcid":false,"given":"Nelson","family":"Andrade","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal"},{"name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde\u2014Tecnologias e Processos Limpos (REQUIMTE\/LAQV), Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-7670","authenticated-orcid":false,"given":"Ilda","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8365-7934","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Marques","sequence":"additional","affiliation":[{"name":"Nutrition & Metabolism, Comprehensive Health Research Centre (CHRC), NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-1622","authenticated-orcid":false,"given":"Juliana A.","family":"Barreto-Peixoto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde\u2014Tecnologias e Processos Limpos (REQUIMTE\/LAQV), Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6767-6596","authenticated-orcid":false,"given":"Maria B. 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