Nononcogenic restoration of the intestinal barrier by E. coli-delivered human EGF.

Abstract

Although mucoactive proteins, such as epidermal growth factor (EGF), could improve clinical outcomes of intestinal ulcerative diseases, their gastrointestinal application is limited because of their proteolytic digestion or concerns about tumor promotion. In the present study, ATP-binding cassette (ABC) transporter-linked secretion of human EGF from probiotic Escherichia coli (EGF-EcN) was created to promote beneficial actions of the EGF receptor, which is notably attenuated in patients with intestinal ulcerative injuries. Preventive and postinjury treatment with EGF-EcN alleviated intestinal ulcers and other readouts of disease severity in murine intestinal ulcer models. EGF-EcN administration promoted the restitutive recovery of damaged epithelial layers, particularly via upward expansion of highly proliferating progenitor cells from the lower crypts. Along with the epithelial barrier benefit, EGF-EcN improved goblet cell-associated mucosal integrity, which controls the access of luminal microbiota to the underlying host tissues. Despite concern about the oncogenic action of EGF, EGF-EcN did not aggravate colitis-associated colon cancer; instead, it alleviated protumorigenic activities and improved barrier integrity in the lesions. All findings indicate that probiotic bacteria-based precision delivery of human EGF is a promising mucosal intervention against gastrointestinal ulcers and malignant distress through crypt-derived barrier restoration.

• Authors: Mira Yu, Juil Kim, Jung Hoon Ahn, Yuseok Moon
• Journal: JCI insight (JCI Insight) Vol. 4 Issue 16 (08 22 2019) ISSN: 2379-3708 [Electronic] United States
• PMID: 31434808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP-Binding Cassette Transporters
• Epidermal Growth Factor

Topics

• ATP-Binding Cassette Transporters (genetics, metabolism)
• Animals
• Cell Line
• Cells, Cultured
• Disease Models, Animal
• Drug Delivery Systems
• Epidermal Growth Factor (administration & dosage, therapeutic use)
• Escherichia coli (genetics, metabolism)
• Female
• Humans
• Inflammatory Bowel Diseases (diet therapy, drug therapy)
• Intestinal Mucosa (drug effects, metabolism)
• Intestinal Neoplasms (diet therapy, drug therapy)
• Mice
• Mice, Inbred C57BL
• Probiotics
• Ulcer (therapy)