title: Sequential release of milk protein-derived bioactive peptides in the jejunum in healthy humans.
abstract: BACKGROUND
  The digestive hydrolysis of dietary proteins leads to the release of peptides in the intestinal tract, where they may exert a variety of functions, but their characterization and quantification are difficult.
  
  
  OBJECTIVE
  We aimed to characterize and determine kinetics of the formation of peptides present in the jejunum of humans who ingested casein or whey proteins by using mass spectrometry and to look for and quantify bioactive peptides.
  
  
  METHODS
  Subjects were equipped with a double-lumen nasogastric tube that migrated to the proximal jejunum. A sample collection was performed for 6 h after the ingestion of 30 g (15)N-labeled casein (n = 7) or whey proteins (WPs; n = 6). Nitrogen flow rates were measured, and peptides were identified by using mass spectrometry.
  
  
  RESULTS
  After casein ingestion, medium-size peptides (750-1050 kDa) were released during 6 h, whereas larger peptides (1050-1800 kDa) were released from WPs in the first 3 h. A total of 356 and 146 peptides were detected and sequenced in the jejunum after casein and WP ingestion, respectively. β-casein was the most important precursor of peptides, including bioactive peptides with various activities. The amounts of β-casomorphins (β-casein 57-, 58-, 59-, and 60-66) and β-casein 108-113 released on the postprandial window were sufficient to elicit the biological action of these peptides (ie, opioid and antihypertensive, respectively).
  
  
  CONCLUSIONS
  Clear evidence is shown of the presence of bioactive peptides in the jejunum of healthy humans who ingested casein. Our findings raise the question about the physiologic conditions under which these peptides can express their bioactivity in humans. This trial was registered at clinicaltrials.gov as NCT00862329.
authors.affiliation: Institut National de la Recherche Agronomique (INRA), joint research unit (UMR) 1253 Science et Technologie du Lait et de l'Œuf, Rennes, France. rachel.boutrou@rennes.inra.fr
authors.forename: Rachel
authors.initials: R
authors.lastname: Boutrou
authors.forename: Claire
authors.initials: C
authors.lastname: Gaudichon
authors.forename: Didier
authors.initials: D
authors.lastname: Dupont
authors.forename: Julien
authors.initials: J
authors.lastname: Jardin
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Airinei
authors.forename: Agnès
authors.initials: A
authors.lastname: Marsset-Baglieri
authors.forename: Robert
authors.initials: R
authors.lastname: Benamouzig
authors.forename: Daniel
authors.initials: D
authors.lastname: Tomé
authors.forename: Joëlle
authors.initials: J
authors.lastname: Leonil
mesh_terms: D000293:Adolescent; D000328:Adult; D002364:Caseins / Q000032:analysis* / Q000378:metabolism*; D002853:Chromatography, Liquid; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage; D004063:Digestion; D004723:Endorphins / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D007700:Kinetics; D008297:Male; D062407:Meals; D008894:Milk Proteins / Q000032:analysis* / Q000378:metabolism*; D009584:Nitrogen / Q000032:analysis / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D016037:Single-Blind Method; D053719:Tandem Mass Spectrometry; D000067816:Whey Proteins; D055815:Young Adult
chemical_list: D002364:Caseins; D004044:Dietary Proteins; D004723:Endorphins; D008894:Milk Proteins; D010455:Peptides; D000067816:Whey Proteins; C021968:beta-casomorphins; D009584:Nitrogen