TY - JOUR
T1 - Exploring the Immunomodulatory Potential of Human Milk
T2 - Aryl Hydrocarbon Receptor Activation and Its Impact on Neonatal Gut Health
AU - Wieser, Naomi V.
AU - Ghiboub, Mohammed
AU - Verseijden, Caroline
AU - van Goudoever, Johannes B.
AU - Schoonderwoerd, Anne
AU - de Meij, Tim G.J.
AU - Niemarkt, Hendrik J.
AU - Davids, Mark
AU - Lefèvre, Antoine
AU - Emond, Patrick
AU - Derikx, Joep P.M.
AU - Jonge, Wouter J.de
AU - Sovran, Bruno
PY - 2024/5/2
Y1 - 2024/5/2
N2 - Several metabolites of the essential amino acid tryptophan have emerged as key players in gut homeostasis through different cellular pathways, particularly through metabolites which can activate the aryl hydrocarbon receptor (AHR). This study aimed to map the metabolism of tryptophan in early life and investigate the effects of specific metabolites on epithelial cells and barrier integrity. Twenty-one tryptophan metabolites were measured in the feces of full-term and preterm neonates as well as in human milk and formula. The ability of specific AHR metabolites to regulate cytokine-induced IL8 expression and maintain barrier integrity was assessed in Caco2 cells and human fetal organoids (HFOs). Overall, higher concentrations of tryptophan metabolites were measured in the feces of full-term neonates compared to those of preterm ones. Within AHR metabolites, indole-3-lactic acid (ILA) was significantly higher in the feces of full-term neonates. Human milk contained different levels of several tryptophan metabolites compared to formula. Particularly, within the AHR metabolites, indole-3-sulfate (I3S) and indole-3-acetic acid (IAA) were significantly higher compared to formula. Fecal-derived ILA and milk-derived IAA were capable of reducing TNFα-induced IL8 expression in Caco2 cells and HFOs in an AHR-dependent manner. Furthermore, fecal-derived ILA and milk-derived IAA significantly reduced TNFα-induced barrier disruption in HFOs.
AB - Several metabolites of the essential amino acid tryptophan have emerged as key players in gut homeostasis through different cellular pathways, particularly through metabolites which can activate the aryl hydrocarbon receptor (AHR). This study aimed to map the metabolism of tryptophan in early life and investigate the effects of specific metabolites on epithelial cells and barrier integrity. Twenty-one tryptophan metabolites were measured in the feces of full-term and preterm neonates as well as in human milk and formula. The ability of specific AHR metabolites to regulate cytokine-induced IL8 expression and maintain barrier integrity was assessed in Caco2 cells and human fetal organoids (HFOs). Overall, higher concentrations of tryptophan metabolites were measured in the feces of full-term neonates compared to those of preterm ones. Within AHR metabolites, indole-3-lactic acid (ILA) was significantly higher in the feces of full-term neonates. Human milk contained different levels of several tryptophan metabolites compared to formula. Particularly, within the AHR metabolites, indole-3-sulfate (I3S) and indole-3-acetic acid (IAA) were significantly higher compared to formula. Fecal-derived ILA and milk-derived IAA were capable of reducing TNFα-induced IL8 expression in Caco2 cells and HFOs in an AHR-dependent manner. Furthermore, fecal-derived ILA and milk-derived IAA significantly reduced TNFα-induced barrier disruption in HFOs.
KW - aryl hydrocarbon receptor
KW - barrier integrity
KW - prematurity
UR - http://www.scopus.com/inward/record.url?scp=85194219556&partnerID=8YFLogxK
U2 - 10.3390/nu16101531
DO - 10.3390/nu16101531
M3 - Article
C2 - 38794769
AN - SCOPUS:85194219556
SN - 2072-6643
VL - 16
JO - Nutrients
JF - Nutrients
IS - 10
M1 - 1531
ER -
