Bovine milk peptide beta-casomorphin-7 alters transcriptomics profiles of gut epithelial cells


Ardıçlı S., Ardıçlı Ö., Yazıcı D., Pat Y., Babayev H., Garcia-Sanchez A., ...Daha Fazla

ALLERGY: EUROPEAN JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, cilt.79, sa.S113, ss.102-103, 2024 (SCI-Expanded)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 79 Sayı: S113
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1111/all.16298
  • Dergi Adı: ALLERGY: EUROPEAN JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, Veterinary Science Database
  • Sayfa Sayıları: ss.102-103
  • Bursa Uludağ Üniversitesi Adresli: Evet

Özet

Background: Bovine beta-casein A2 milk is becoming increasingly popular, with both producers and consumers demonstrating a rising inclination towards its production. In the beta-casein locus, alleles A1 and A2 exhibit disparity at amino acid position 67, wherein A1 codes for histidine and A2 codes for proline. The breakdown of A1 beta-casein leads to the generation of beta-casomorphin (BCM)-7, a bioactive peptide possessing morphine-like properties. The increasing preference for A2 milk is often attributed to its perceived benefits, particularly its potential to elicit fewer inflammatory responses compared to A1 milk. However, the understanding of this subject remains limited. This study aims to comprehensively examine the effects of BCM-7 and BCM-9, bioactive peptides resulting from the digestion of A1 and A2 milk, respectively, on the integrity of the gut epithelial barrier.

Method: A microfluidic gut-on-a-chip plate was employed to form a tubular barrier utilizing Caco-2 cells, enabling the assessment of the impacts of BCMs on gut epithelial cells and their barrier function. The concentrations of peptides utilized in the study were selected based on their relevance in vivo, considering the presence of these compounds in raw milk or cheese. Following cytotoxicity assessment, transepithelial electrical resistance (TER) measurement, paracellular permeability assay, wound healing assay, targeted proteomics using proximity extension assay, untargeted proteomics, and RNA sequencing were performed.

Results: Monolayer cultures did not exhibit cytotoxicity upon exposure to bovine BCM-7 and BCM-9. In addition, no significant findings were observed in the targeted proteomics assessment. Based on RNA sequencing results, alterations in the expression profile of 231 genes were identified with BCM-7 (20 ug/ml), while BCM-9 did not show any significant transcriptome changes. Among these, KLHDC7B, HOOK3, PKD1P2, G6PC1, L3MBTL1, IDI2-AS1, and DDX60L genes showed the highest upregulation (2.27 to 3.50 fold), while TFDP2, ANAPC13, and CXCL8 genes demonstrated the most significant downregulation (−2.47 to −2.61 fold). Pathway analysis highlighted pathways associated with cellular metabolism and biogenesis, encompassing signal transduction, organelle organization and biogenesis, cytoskeleton, and microtubule organization, as well as cell cycle checkpoints.

Conclusion: Taken together, while BCM-7 showed significant differences in transcriptomic profiling, BCM-9 displayed an inactive nature to Caco2 cells. Conflicts of interest: The authors did not specify any links of interest.