{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:08:30Z","timestamp":1785146910910,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Ultra-processed foods expose consumers to heat-induced contaminants like 5-hydroxymethylfurfural (5-HMF), which impairs intestinal homeostasis via oxidative stress and inflammation. This study quantified 5-HMF in bakery products and evaluated blueberry polyphenols\u2019 capacity to attenuate 5-HMF-induced cellular stress in an in vitro Caco-2 intestinal model. 5-HMF levels in commercial bakery products were determined using a colorimetric assay and HPLC-UV. Differentiated Caco-2 cells were exposed to 5-HMF (0.4 mM) for 48 h, alone or co-treated with blueberry juice (15 \u00b5g\/mL of phenol equivalents). ROS production, lipid accumulation, gene expression of antioxidant, lipid, and inflammatory markers, and NF-\u03baB\/ERK signaling pathways were analyzed. HPLC-UV accurately quantified 5-HMF in bakery products (exceeding 2 mg\/100 g), revealing systematic overestimation by the colorimetric method. In Caco-2 cells, 5-HMF significantly increased ROS, lipid accumulation, inflammatory cytokines (NLRP3, IL1B, and IL18), and activated NF-\u03baB and p-ERK. Co-treatment with blueberry juice reduced ROS and lipids, upregulated the NRF2 antioxidant pathway, and drastically suppressed NF-\u03baB -mediated inflammation. 5-HMF induced markers of metabolic dysfunction, oxidative stress, and inflammation in the intestinal epithelial model. Polyphenol-rich blueberry juice attenuated 5-HMF-induced alterations at the tested concentration, suggesting a potential protective nutritional strategy against epithelial stress associated with food-processing contaminants.<\/jats:p>","DOI":"10.3390\/ijms27156665","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"6665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Dietary 5-Hydroxymethylfurfural-Induced Intestinal Epithelial Stress by Blueberry Polyphenols"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0881-4036","authenticated-orcid":false,"given":"Rosario","family":"Mare","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9293-1433","authenticated-orcid":false,"given":"Francesca Rita","family":"Noto","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0441-6710","authenticated-orcid":false,"given":"Martina","family":"Rago","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-3949","authenticated-orcid":false,"given":"Kardelen","family":"Aslan","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Galluccio","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Unit, Renato Dulbecco Hospital, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2475-3624","authenticated-orcid":false,"given":"Luana Carmen","family":"Mirabello","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7926-2981","authenticated-orcid":false,"given":"Ilenia","family":"Lio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7644-1337","authenticated-orcid":false,"given":"Samantha","family":"Maurotti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fclhan","family":"Samur","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Pujia","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"},{"name":"Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7048-5830","authenticated-orcid":false,"given":"Tiziana","family":"Montalcini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"},{"name":"Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.chroma.2006.09.023","article-title":"Analysis of 5-hydroxymethylfurfural in foods by gas chromatography-mass spectrometry","volume":"1135","author":"Teixido","year":"2006","journal-title":"J. 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