Beyond A1 milk concerns: dietary-relevant concentrations of beta-casomorphin-7 show limited absorption but retain opioid-like activity in an intestinal cell model

Fuente: "milk OR dairy products"
Food Funct. 2026 Mar 9. doi: 10.1039/d5fo04465k. Online ahead of print.ABSTRACTMilk and dairy products are a significant source of bioactive peptides, including β-casomorphin-7 (BCM-7), a heptapeptide released from the enzymatic cleavage of the A1 variant of β-casein. While some studies have suggested that BCM-7 may have detrimental effects on gastrointestinal physiology, the European Food Safety Authority found no established cause-and-effect relationship between the oral intake of BCM-7 and non-communicable diseases. This study aimed to investigate the biological effects of BCM-7 at physiologically relevant concentrations, corresponding to the estimated exposure levels in the European population, on the mucus-producing HT29-MTX-E12 intestinal cell line. Cells were treated with BCM-7 concentrations ranging from 4 to 120 µM for 4 hours, and various endpoints were assessed, including cytotoxicity, mucus production and secretion, opioid activity, inflammation, and peptide translocation across the intestinal barrier. BCM-7 treatment did not significantly affect cell viability, metabolic activity, or membrane integrity, except for a slight increase in LDH release at the highest concentration tested. No changes in mucin gene transcription levels (MUC5AC, MUC2) or mucus secretion were observed. However, BCM-7 treatment increased the expression of the µ-opioid receptor compared to the untreated control, confirming its opioid-like properties. While the IL-8 gene mRNA level increased at 120 µM, protein secretion remained unchanged, suggesting limited inflammatory effect. BCM-7 translocation across the intestinal barrier was minimal and inversely concentration-dependent, with most peptides likely degraded by dipeptidyl peptidase-4. These findings demonstrate that physiologically relevant BCM-7 concentrations exhibit opioid-like properties but have limited impact on mucus production, inflammation, and translocation of the intact peptide across the epithelial barrier in this in vitro intestinal model. The results provide mechanistic insights into BCM-7 effects while highlighting the need for further research considering individual dietary patterns and complex milk component interactions.PMID:41801106 | DOI:10.1039/d5fo04465k