Repeated aluminum ingestion alters human intestinal structure: focus on advanced 3D tissue models.

Giulia De Negri Atanasio, Lorenzo Dondero, Francesca Tardanico, Giorgia Allaria, Erica Lertora, Giacomo Rosa, Chiara Barisione, Caterina Ivaldo, Francesca Rispo, Tommaso Filippini, Ilaria Demori, Sara Ferrando, Maria Cristina Gagliani, Katia Cortese, Mario Passalacqua, Jan Markus, Silvia Letasiova, Elena Grasselli

Journal: Pflugers Archiv : European journal of physiology 2026;478(7):

PMID: 42420558

Full Text on Springer View on PubMed

Abstract

Aluminum (Al³⁺) is a widespread environmental metal with potential effects on the intestinal epithelium. In this study, we evaluated the impact of dietary concentrations of aluminum on barrier integrity, histological organization, and gene expression in a 3D human intestinal tissue model. Tissues were exposed to increasing concentrations of aluminum (0, 5, 20, and 50 ppm) for 12 days to mimic environmental chronic exposure through ingestion. Transepithelial electrical resistance (TEER) measurements revealed a significant decrease only at the highest dose (50 ppm) on day 12, indicating a damage to the epithelial permeability. This was supported by a marked downregulation of OCLN and CLDN-5 expression, key genes involved in tight junction integrity. Aluminum permeation across the tissue was confirmed via Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES), indicating dose-dependent penetration. Furthermore, gene expression analysis showed significant upregulation of MT-1E and MT-2 A (markers of cellular response to metal exposure) while MT-1 A remained unchanged. The present data demonstrate that repeated exposure to 50 ppm of Al3+ impacts intestinal barrier function and alters the tissue organization in the human intestinal epithelium.

Address: Department of Earth, Environment and Life Science, University of Genoa, Genova, Italy.; Interuniversity Center for the Promotion of 3R Principles in Teaching and Research (Centro 3R), Pisa, Italy.; Department of Earth, Environment and Life Science, University of Genoa, Genova, Italy.; Angel Consulting srl, Via San Senatore 14, Milano, 20122, Italy.; Department of Earth, Environment and Life Science, University of Genoa, Genova, Italy.; National Biodiversity Future Center (NFBC), Piazza Marina, 61, Palermo, 90133, Italy.; Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, Viale Benedetto XV,6, Genoa, 16132, Italy.; IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, Genoa, 16132, Italy.; Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), Department of Biomedical, Metabolic and Neural Sciences, Section of Public Health, University of Modena and Reggio Emilia, Modena, Italy.; School of Public Health, University of California Berkeley, Berkeley, CA, USA.; Department of Pharmacy, University of Genoa, Genova, Italy.; Department of Experimental Medicine, University of Genoa, Genoa, Italy.; Interuniversity Center for the Promotion of 3R Principles in Teaching and Research (Centro 3R), Pisa, Italy.; Department of Experimental Medicine, University of Genoa, Genoa, Italy.; MatTek Now Part of Sartorius, Bratislava, Slovakia.; Department of Earth, Environment and Life Science, University of Genoa, Genova, Italy. [email protected].; Interuniversity Center for the Promotion of 3R Principles in Teaching and Research (Centro 3R), Pisa, Italy. [email protected].; National Center for the Development of New Technologies in Agriculture (Agritech), Napoli, Italy. [email protected].; Istituto Nazionale Biostrutture e Biosistemi (INBB), Roma, 00136, Italy. [email protected].

DOI: 10.1007/s00424-026-03191-y

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https://dx.doi.org/10.1007/s00424-026-03191-y

MeSH Terms: Humans, Aluminum, Intestinal Mucosa, Intestinal Barrier Function, Tight Junctions, Occludin, Permeability