{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:08:42Z","timestamp":1789132122962,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Universities and Research","award":["2022RB7938"],"award-info":[{"award-number":["2022RB7938"]}]},{"name":"Italian Ministry of Universities and Research","award":["J53D23012360006"],"award-info":[{"award-number":["J53D23012360006"]}]},{"award":["2022RB7938"],"award-info":[{"award-number":["2022RB7938"]}],"id":[{"id":"https:\/\/ror.org\/0341vw408","id-type":"ROR","asserted-by":"publisher"}]},{"award":["J53D23012360006"],"award-info":[{"award-number":["J53D23012360006"]}],"id":[{"id":"https:\/\/ror.org\/0341vw408","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Citrus processing by-products represent a sustainable source of bioactive plant complexes with potential applications in intestinal health. This study investigated the effects of standardized food-grade orange (OE) and lemon (LE) pomace extracts and their simulated gastrointestinal digestates (DIGs) on intestinal epithelial responses and selected probiotic strains. Caco-2 cells were used to assess cytotoxicity, epithelial wound closure, and, in differentiated monolayers challenged with lipopolysaccharide (LPS), extracellular levels of SOD2, catalase, Nrf2, IL-6, IL-8, TNF-\u03b1, and IL-1\u03b2. In parallel, the effects of OE, LE, and their corresponding DIGs on the growth and cell-surface hydrophobicity of four probiotic lactic acid bacteria were evaluated. OE and LE DIGs were non-cytotoxic and promoted epithelial wound closure in a concentration- and time-dependent manner. In LPS-challenged monolayers, both DIGs counteracted alterations in extracellular oxidative stress-related proteins and reduced pro-inflammatory cytokine levels without affecting cell viability. OE and LE also produced strain-dependent effects on probiotic growth and cell-surface hydrophobicity, which were modified by gastrointestinal digestion. Overall, these findings extend previous evidence on the intestinal bioactivity of Citrus pomace-derived plant complexes and support their further investigation as sustainable food-grade ingredients for gut health applications.<\/jats:p>","DOI":"10.3390\/antiox15091161","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:24:33Z","timestamp":1789129473000},"page":"1161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Citrus Pomace-Derived Plant Complexes Enhance Caco-2 Wound Closure In Vitro and Modulate Selected Probiotic Strains"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7976-532X","authenticated-orcid":false,"given":"Mariarosaria","family":"Ingegneri","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Martina","family":"Imbesi","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Souda","family":"Belaid","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6945-7145","authenticated-orcid":false,"given":"Marta","family":"Mangano","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2437-9276","authenticated-orcid":false,"given":"Maria Neve","family":"Ombra","sequence":"additional","affiliation":[{"name":"Institute of Food Science, ISA-CNR, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5759-7499","authenticated-orcid":false,"given":"Filomena","family":"Nazzaro","sequence":"additional","affiliation":[{"name":"Institute of Food Science, ISA-CNR, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-304X","authenticated-orcid":false,"given":"Antonella","family":"Smeriglio","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4358-5224","authenticated-orcid":false,"given":"Domenico","family":"Trombetta","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2350631","DOI":"10.1002\/eji.202350631","article-title":"Epithelial-immune cell crosstalk for intestinal barrier homeostasis","volume":"54","author":"Yao","year":"2024","journal-title":"Eur. J. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Stojanovic, B., Milivojcevic Bevc, I., Dimitrijevic Stojanovic, M., Stojanovic, B.S., Jovanovic, M., Lazarevic, S., Milosevic, B., Radosavljevic, I., Tasic-Uros, D., and Markovic, N. (2025). Nrf2 as a molecular guardian of redox balance and barrier integrity in IBD. Antioxidants, 14.","DOI":"10.3390\/antiox14121407"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sun, Y., Wang, X., Li, L., Zhong, C., Zhang, Y., Yang, X., Li, M., and Yang, C. (2024). The role of gut microbiota in intestinal disease: From an oxidative stress perspective. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1328324"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4306","DOI":"10.1007\/s10620-023-08122-w","article-title":"Intestinal barrier dysfunction in inflammatory bowel disease: Underpinning pathogenesis and therapeutics","volume":"68","author":"Dunleavy","year":"2023","journal-title":"Dig. Dis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Capaldo, C.T. (2023). Claudin barriers on the brink: How conflicting tissue and cellular priorities drive IBD pathogenesis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108562"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41575-023-00766-3","article-title":"Paracellular permeability and tight junction regulation in gut health and disease","volume":"20","author":"Horowitz","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Matar, A., Damianos, J.A., Jencks, K.J., and Camilleri, M. (2024). Intestinal barrier impairment, preservation, and repair: An update. Nutrients, 16.","DOI":"10.3390\/nu16203494"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.3748\/wjg.v29.i10.1539","article-title":"Precision medicine in inflammatory bowel disease: Individualizing the use of biologics and small molecule therapies","volume":"29","author":"Cheah","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1053\/j.gastro.2023.10.033","article-title":"Integrating evidence to guide use of biologics and small molecules for inflammatory bowel diseases","volume":"166","author":"Dulai","year":"2024","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lin, P.Y., Stern, A., Peng, H.H., Chen, J.H., and Yang, H.C. (2022). Redox and metabolic regulation of intestinal barrier function and associated disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214463"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102950","DOI":"10.1016\/j.redox.2023.102950","article-title":"The effect of iron therapy on oxidative stress and intestinal microbiota in inflammatory bowel diseases: A review on the conundrum","volume":"68","author":"Loveikyte","year":"2023","journal-title":"Redox Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/dvdy.500","article-title":"Regulation of homeostasis and regeneration in the adult intestinal epithelium by the TGF-\u03b2 superfamily","volume":"252","author":"Fink","year":"2023","journal-title":"Dev. Dyn."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4878","DOI":"10.1039\/D0FO00713G","article-title":"Synergic interactions between polyphenols and gut microbiota in mitigating inflammatory bowel diseases","volume":"11","author":"Li","year":"2020","journal-title":"Food Funct."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5658","DOI":"10.1080\/10408398.2021.1888693","article-title":"The synergistic and antagonistic antioxidant interactions of dietary phytochemical combinations","volume":"62","author":"Chen","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1146\/annurev-food-052720-100326","article-title":"Current understanding of modes of action of multicomponent bioactive phytochemicals: Potential for nutraceuticals and antimicrobials","volume":"13","author":"Wink","year":"2022","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Stevens, Y., Rymenant, E.V., Grootaert, C., Camp, J.V., Possemiers, S., Masclee, A., and Jonkers, D. (2019). The intestinal fate of citrus flavanones and their effects on gastrointestinal health. Nutrients, 11.","DOI":"10.3390\/nu11071464"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/1541-4337.12652","article-title":"Citrus flavonoids and the intestinal barrier: Interactions and effects","volume":"20","author":"Wang","year":"2021","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Barreca, D., Mandalari, G., Calderaro, A., Smeriglio, A., Trombetta, D., Felice, M.R., and Gattuso, G. (2020). Citrus flavones: An update on sources, biological functions, and health promoting properties. Plants, 9.","DOI":"10.3390\/plants9030288"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1017\/S0007114521004797","article-title":"The effects of citrus flavonoids and their metabolites on immune-mediated intestinal barrier disruption using an in vitro co-culture model","volume":"128","author":"Stevens","year":"2022","journal-title":"Br. J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kho, Z.Y., and Lal, S.K. (2018). The human gut microbiome\u2014A potential controller of wellness and disease. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01835"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.jnutbio.2013.05.001","article-title":"Benefits of polyphenols on gut microbiota and implications in human health","volume":"24","author":"Cardona","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ingegneri, M., Braghini, M.R., Piccione, M., De Stefanis, C., Mandrone, M., Chiocchio, I., Poli, F., Imbesi, M., Alisi, A., and Smeriglio, A. (2024). Citrus pomace as a source of plant complexes to be used in the nutraceutical field of intestinal inflammation. Antioxidants, 13.","DOI":"10.3390\/antiox13070869"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Smeriglio, A., La Neve, A., Mangano, M., Imbesi, M., Cornara, L., and Trombetta, D. (2025). Rediscovering Citrus lumia \u2018Pyriformis\u2019: Phytochemical profile and multifunctional properties of its fresh juice. Foods, 14.","DOI":"10.3390\/foods14233997"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Russo, C., Maugeri, A., Lombardo, G.E., Musumeci, L., Barreca, D., Rapisarda, A., Cirmi, S., and Navarra, M. (2021). The second life of citrus fruit waste: A valuable source of bioactive compounds. Molecules, 26.","DOI":"10.3390\/molecules26195991"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/10408398.2021.1943647","article-title":"Citrus processing by-products: An overlooked repository of bioactive compounds","volume":"63","author":"Kaur","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/s41596-018-0119-1","article-title":"INFOGEST static in vitro simulation of gastrointestinal food digestion","volume":"14","author":"Brodkorb","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"348","DOI":"10.3748\/wjg.14.348","article-title":"Epithelial restitution and wound healing in inflammatory bowel disease","volume":"14","author":"Sturm","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, M., Shi, J., Yu, C., Zhang, X., Xu, G., Xu, Z., and Ma, Y. (2023). Emerging strategy towards mucosal healing in inflammatory bowel disease: What the future holds?. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1298186"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1136\/gutjnl-2012-302830","article-title":"Mucosal healing in inflammatory bowel diseases: A systematic review","volume":"61","author":"Neurath","year":"2012","journal-title":"Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1078\/0944-7113-00060","article-title":"Synergy and other interactions in phytomedicines","volume":"8","author":"Williamson","year":"2001","journal-title":"Phytomedicine"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sahoo, D.K., Heilmann, R.M., Paital, B., Patel, A., Yadav, V.K., Wong, D., and Jergens, A.E. (2023). Oxidative stress, hormones, and effects of natural antioxidants on intestinal inflammation in inflammatory bowel disease. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1217165"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.molmed.2023.07.008","article-title":"The NRF2\/Keap1 pathway as a therapeutic target in inflammatory bowel disease","volume":"29","author":"Geertsema","year":"2023","journal-title":"Trends Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"105243","DOI":"10.1016\/j.phrs.2020.105243","article-title":"The Nrf2 in the pathophysiology of the intestine: Molecular mechanisms and therapeutic implications for inflammatory bowel diseases","volume":"163","author":"Piotrowska","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"eadh1641","DOI":"10.1126\/scisignal.adh1641","article-title":"The NF-\u03baB signaling system in the immunopathogenesis of inflammatory bowel disease","volume":"17","author":"Mukherjee","year":"2024","journal-title":"Sci. Signal."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ozdal, T., Sela, D.A., Xiao, J., Boyacioglu, D., Chen, F., and Capanoglu, E. (2016). The reciprocal interactions between polyphenols and gut microbiota and effects on bioaccessibility. Nutrients, 8.","DOI":"10.3390\/nu8020078"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1574-6968.2006.00291.x","article-title":"Microbial adhesion to hydrocarbons: Twenty-five years of doing MATH","volume":"262","author":"Rosenberg","year":"2006","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1046\/j.1365-2672.2003.01915.x","article-title":"Adhesion and aggregation ability of probiotic strain Lactobacillus acidophilus M92","volume":"94","author":"Kos","year":"2003","journal-title":"J. Appl. Microbiol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/9\/1161\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:32:22Z","timestamp":1789129942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/9\/1161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["antiox15091161"],"URL":"https:\/\/doi.org\/10.3390\/antiox15091161","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}