A peptidomic analysis of human milk digestion in the infant stomach reveals protein-specific degradation patterns.
In vitro digestion of isolated milk proteins results in milk peptides with a variety of actions. However, it remains unclear to what degree protein degradation occurs in vivo in the infant stomach and whether peptides previously annotated for bioactivity are released. This study combined nanospray LC separation with time-of-flight mass spectrometry, comprehensive structural libraries, and informatics to analyze milk from 3 human mothers and the gastric aspirates from their 4- to 12-d-old postpartum infants. Milk from the mothers contained almost 200 distinct peptides, demonstrating enzymatic degradation of milk proteins beginning either during lactation or between milk collection and feeding. In the gastric samples, 649 milk peptides were identified, demonstrating that digestion continues in the infant stomach. Most peptides in both the intact milk and gastric samples were derived from β-casein. The numbers of peptides from β-casein, lactoferrin, α-lactalbumin, lactadherin, κ-casein, serum albumin, bile salt-associated lipase, and xanthine dehydrogenase/oxidase were significantly higher in the gastric samples than in the milk samples (P < 0.05). A total of 603 peptides differed significantly in abundance between milk and gastric samples (P < 0.05). Most of the identified peptides have previously identified biologic activity. Gastric proteolysis occurs in the term infant in the first 2 wk of life, releasing biologically active milk peptides with immunomodulatory and antibacterial properties of clinical relevance to the proximal intestinal tract. Data are available via ProteomeXchange (identifier PXD000688).
Department of Food Science Foods for Health Institute, and dcdallas@ucdavis.edu.
David C
DC
Dallas
Department of Chemistry, University of California at Davis, Davis, CA.
Andrés
A
Guerrero
Department of Food Science University College Dublin Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Sciences, UCD Complex and Adaptive Systems Laboratory, University College Dublin, Dublin, Republic of Ireland; and.
Nora
N
Khaldi
Department of Pediatrics, University of California at Davis, Sacramento, CA.
Robyn
R
Borghese
Department of Food Science.
Aashish
A
Bhandari
Foods for Health Institute, and Department of Pediatrics, University of California at Davis, Sacramento, CA.
Mark A
MA
Underwood
Foods for Health Institute, and Department of Chemistry, University of California at Davis, Davis, CA.
Carlito B
CB
Lebrilla
Department of Food Science Foods for Health Institute, and.
J Bruce
JB
German
Department of Food Science Foods for Health Institute, and.
Daniela
D
Barile
D001647:Bile Acids and Salts / Q000032:analysis; D001942:Breast Feeding; D002364:Caseins / Q000032:analysis; D004063:Digestion / Q000502:physiology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000378:metabolism; D007768:Lactalbumin / Q000032:analysis; D007774:Lactation; D007781:Lactoferrin / Q000032:analysis; D008297:Male; D008894:Milk Proteins / Q000032:analysis*; D008895:Milk, Human / Q000737:chemistry*; D010455:Peptides / Q000032:analysis; D059748:Proteolysis; D012709:Serum Albumin / Q000032:analysis; D014968:Xanthine Dehydrogenase / Q000032:analysis
D001647:Bile Acids and Salts; D002364:Caseins; D008894:Milk Proteins; D010455:Peptides; D012709:Serum Albumin; D007768:Lactalbumin; D014968:Xanthine Dehydrogenase; D007781:Lactoferrin