Spp24 is associated with endocytic signalling, lipid metabolism, and discrimination of tissue integrity for ‘leaky-gut’ in inflammatory bowel disease

Valerie C. Wasinger*, Kenneth Lu, Yunki Y. Yau, Justin Nash, Jess Lee, Jeff Chang, Sudarshan Paramsothy, Nadeem O. Kaakoush, Hazel M. Mitchell, Rupert W. L. Leong

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Epithelial barrier injury allows contaminants to cross-over into the blood stream and trigger an inflammatory response, contributing to inflammatory bowel disease (IBD). Currently there is no single test that can reliably diagnose intestinal mucosal barrier function or measure impaired epithelial cell integrity associated with increasing permeability. Here, we assess the association between serum proteins and small intestinal permeability as detected by confocal laser endomicroscopy (CLE); in particular the known IBD marker—secreted phosphoprotein 24 (SPP24) and its binding partners; and use developed monoclonal antibodies to assess the role of SPP24 in mucosal healing. Sera were obtained from 28 IBD patients and non-IBD controls undergoing CLE with scores ranging from low to high permeability, as well as active ulcerative colitis from 53 patients undergoing fecal microbiota transplant therapy (FMT). Higher permeability associated with altered lipid metabolism, heightened innate immune response and junctional protein signalling in UC patients. A correlation between increasing leak and SPP24 peptide was observed. There is a strong indication of the novel role of SPP24 in gut barrier dysfunction particularly in ulcerative colitis. Its correlation to the established CLE for monitoring permeability has the potential to provide a blood based parallel to monitor and guide therapy more readily across a broad spectrum of illnesses for which ‘leak’ dominates the pathology.

Original languageEnglish
Article number12932
Pages (from-to)1-11
Number of pages11
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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