TY - JOUR
T1 - Hypoxia-Driven Changes in a Human Intestinal Organoid Model and the Protective Effects of Hydrolyzed Whey
AU - de Lange, Ilse H.
AU - van Gorp, Charlotte
AU - Massy, Kimberly R. I.
AU - Kessels, Lilian
AU - Kloosterboer, Nico
AU - Bj?rnshave, Ann
AU - Stampe Ostenfeld, Marie
AU - Damoiseaux, Jan G. M. C.
AU - Derikx, Joep P. M.
AU - van Gemert, Wim G.
AU - Wolfs, Tim G. A. M.
N1 - Funding Information: This work was funded by the NUTRIM Graduate Programme (I.H.d.L.), Arla Foods Ingredients Group P/S and Kinderonderzoeksfonds Limburg (T.G.A.M.W.). Funding Information: This study was financially supported, and whey protein fractions were provided by Arla Foods Ingredients, Viby J., Denmark. Arla Food Ingredients was not involved in the experimental design, (statistical) analysis, or data presentation. Publisher Copyright: © 2023 by the authors.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Many whey proteins, peptides and protein-derived amino acids have been suggested to improve gut health through their anti-oxidant, anti-microbial, barrier-protective and immune-modulating effects. Interestingly, although the degree of hydrolysis influences peptide composition and, thereby, biological function, this important aspect is often overlooked. In the current study, we aimed to investigate the effects of whey protein fractions with different degrees of enzymatic hydrolysis on the intestinal epithelium in health and disease with a novel 2D human intestinal organoid (HIO) monolayer model. In addition, we aimed to assess the anti-microbial activity and immune effects of the whey protein fractions. Human intestinal organoids were cultured from adult small intestines, and a model enabling apical administration of nutritional components during hypoxia-induced intestinal inflammation and normoxia (control) in crypt-like and villus-like HIO was established. Subsequently, the potential beneficial effects of whey protein isolate (WPI) and two whey protein hydrolysates with a 27.7% degree of hydrolysis (DH28) and a 50.9% degree of hydrolysis (DH51) were assessed. In addition, possible immune modulatory effects on human peripheral immune cells and anti-microbial activity on four microbial strains of the whey protein fractions were investigated. Exposure to DH28 prevented paracellular barrier loss of crypt-like HIO following hypoxia-induced intestinal inflammation with a concomitant decrease in hypoxia inducible factor 1 alpha (HIF1α) mRNA expression. WPI increased Treg numbers and Treg expression of cluster of differentiation 25 (CD25) and CD69 and reduced CD4+ T cell proliferation, whereas no anti-microbial effects were observed. The observed biological effects were differentially mediated by diverse whey protein fractions, indicating that (degree of) hydrolysis influences their biological effects. Moreover, these new insights may provide opportunities to improve immune tolerance and promote intestinal health.
AB - Many whey proteins, peptides and protein-derived amino acids have been suggested to improve gut health through their anti-oxidant, anti-microbial, barrier-protective and immune-modulating effects. Interestingly, although the degree of hydrolysis influences peptide composition and, thereby, biological function, this important aspect is often overlooked. In the current study, we aimed to investigate the effects of whey protein fractions with different degrees of enzymatic hydrolysis on the intestinal epithelium in health and disease with a novel 2D human intestinal organoid (HIO) monolayer model. In addition, we aimed to assess the anti-microbial activity and immune effects of the whey protein fractions. Human intestinal organoids were cultured from adult small intestines, and a model enabling apical administration of nutritional components during hypoxia-induced intestinal inflammation and normoxia (control) in crypt-like and villus-like HIO was established. Subsequently, the potential beneficial effects of whey protein isolate (WPI) and two whey protein hydrolysates with a 27.7% degree of hydrolysis (DH28) and a 50.9% degree of hydrolysis (DH51) were assessed. In addition, possible immune modulatory effects on human peripheral immune cells and anti-microbial activity on four microbial strains of the whey protein fractions were investigated. Exposure to DH28 prevented paracellular barrier loss of crypt-like HIO following hypoxia-induced intestinal inflammation with a concomitant decrease in hypoxia inducible factor 1 alpha (HIF1α) mRNA expression. WPI increased Treg numbers and Treg expression of cluster of differentiation 25 (CD25) and CD69 and reduced CD4+ T cell proliferation, whereas no anti-microbial effects were observed. The observed biological effects were differentially mediated by diverse whey protein fractions, indicating that (degree of) hydrolysis influences their biological effects. Moreover, these new insights may provide opportunities to improve immune tolerance and promote intestinal health.
KW - gut organoid
KW - hypoxia
KW - intestinal barrier function
KW - necrotizing enterocolitis
KW - whey protein
UR - http://www.scopus.com/inward/record.url?scp=85146814415&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/nu15020393
DO - https://doi.org/10.3390/nu15020393
M3 - Article
C2 - 36678267
SN - 2072-6643
VL - 15
JO - NUTRIENTS
JF - NUTRIENTS
IS - 2
M1 - 393
ER -