Academic Journal
Protein substitutes used in the treatment of phenylketonuria distinctly modulate gut nutrient absorption and bacterial growth: An in vitro study.
| Τίτλος: | Protein substitutes used in the treatment of phenylketonuria distinctly modulate gut nutrient absorption and bacterial growth: An in vitro study. |
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| Συγγραφείς: | Rodrigues C; Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; Nutrition & Metabolism, CHRC, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal., Ismael S; Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; Nutrition & Metabolism, CHRC, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; Nutrition & Metabolism, CINTESIS@RISE, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal., Monteiro AR; Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Porto, Portugal., Almeida MJ; Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal., Noronha T; Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal., Maia-Santos G; Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; Nutrition & Metabolism, CHRC, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal., Fernandes I; LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Porto, Portugal., Calhau C; Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; Nutrition & Metabolism, CINTESIS@RISE, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal., MacDonald A; Dietetic Department, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, UK., Rocha JC; Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; Nutrition & Metabolism, CHRC, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; Nutrition & Metabolism, CINTESIS@RISE, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; Reference Centre of Inherited Metabolic Diseases, Unidade Local de Saúde São José, Lisboa, Portugal., Araújo JR; Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; Nutrition & Metabolism, CINTESIS@RISE, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal., Faria A; Nutrition & Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal; Nutrition & Metabolism, CHRC, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal. Electronic address: ana.faria@nms.unl.pt. |
| Πηγή: | Nutrition research (New York, N.Y.) [Nutr Res] 2026 Jul; Vol. 151, pp. 37-51. Date of Electronic Publication: 2026 Apr 28. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 8303331 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0739 (Electronic) Linking ISSN: 02715317 NLM ISO Abbreviation: Nutr Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2004- > : Tarrytown, NY : Elsevier Science Original Publication: New York : Pergamon Press, c1981- |
| Ιατρικοί όροι (MeSH): | Caseins*/pharmacology , Amino Acids*/pharmacology , Phenylketonurias*/drug therapy , Intestinal Absorption*/drug effects , Gastrointestinal Microbiome*/drug effects , Dietary Proteins*/pharmacology, Whey Proteins/pharmacology ; Glucose/metabolism ; Fatty Acids/metabolism ; Escherichia coli/growth & development ; Escherichia coli/drug effects ; Humans ; Caco-2 Cells ; Phenylalanine ; Peptide Fragments |
| Περίληψη: | Low phenylalanine (Phe) protein substitutes (PS), either l-amino acids (L-AAs) or casein glycomacropeptide with added amino acids (CGMP-AAs) are the mainstay of phenylketonuria (PKU) treatment. Given the central role of intestinal nutrient absorption and gut microbiota in metabolic regulation, this study investigated how different PS affect nutrient absorption and bacterial growth. It was hypothesized that l-AAs and CGMP-AAs would exert distinct effects. Caco-2 cells, an in vitro model of enterocytes, were used to assess the acute effects of PS and whey protein (WP) on glucose, amino acids, and fatty acids analogues uptake, as well as the longer-term effects on nutrient transporter gene expression. The growth and metabolite production of Escherichia coli, Lactobacillus paracasei, and Shigella flexneri were also assessed. l-AAs reduced glucose absorption and downregulated glucose transporter 2 (GLUT2). Although l-AAs did not affect amino acids or fatty acids absorption, they downregulated l-type amino acid transporter 1 (LAT1) and peptide transporter 1 (PEPT1). CGMP-AAs had no effect on glucose or fatty acid absorption but impaired amino acid absorption and upregulated LAT1. These findings demonstrate formulation-specific effects on nutrient absorption and transporter gene expression. All PS increased bacterial abundance, with l-AAs producing the most pronounced effect relative to CGMP-AAs. l-AAs and WP accelerated the growth rate of all bacterial species, whereas CGMP-AAs selectively promoted the growth of L. paracasei, indicating a potential prebiotic-like effect. In conclusion, PS distinctly modulate intestinal nutrient transport and bacterial growth, underscoring the importance of considering their specific metabolic impact in PKU and the need for further translational research. (Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Author declarations Anita MacDonald has received research funding and honoraria from Nutricia, Vitaflo International and Merck Serono. She is a member of the European Nutritionist Expert Panel (Biomarin), a member of Sapropterin Advisory Board (Biomarin), a member of the advisory board entitled ELEMENT (Danone-Nutricia), and a member of an advisory board for Arla and Applied Pharma Research. Catarina Rodrigues received honoraria as a speaker from PIAM, and her travel to conferences has been supported by both PIAM and PTC. Júlio César Rocha is member of the European Nutrition Expert Panel (Biomarin) and of the advisory boards of Applied Pharma Research, BioMarin, PTC and Nutricia. He has received speaker’s fees from Applied Pharma Research, Merck Serono, BioMarin, Nutricia, Vitaflo, Cambrooke, PIAM, Lifediet, and PTC. |
| Contributed Indexing: | Keywords: Bacterial growth; Caco-2 cells; Gut bacteria; Nutrient absorption; Phenylketonuria; Protein substitutes |
| Substance Nomenclature: | 0 (Caseins) 0 (Amino Acids) 0 (caseinomacropeptide) 0 (Whey Proteins) IY9XDZ35W2 (Glucose) 0 (Fatty Acids) 47E5O17Y3R (Phenylalanine) 0 (Dietary Proteins) 0 (Peptide Fragments) |
| Entry Date(s): | Date Created: 20260525 Date Completed: 20260616 Latest Revision: 20260616 |
| Update Code: | 20260617 |
| DOI: | 10.1016/j.nutres.2026.04.013 |
| PMID: | 42184731 |
| Βάση Δεδομένων: | MEDLINE |
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