Milk protein digestion and the gut microbiome influence gastrointestinal discomfort after cow milk consumption in healthy subjects

•Thirty-one bioactive peptides from milk digestion are identified in human plasma.•Subjects with gastrointestinal discomfort show lower circulating bioactive peptides.•Plasma peptides opioid agonists and antagonists affect gastrointestinal discomfort.•Milk derived-DPPIV inhibitors in plasma affect serum DPPIV activity.•Gut microbiome proteolytic activity may affect gastrointestinal discomfort.