Ganglioside Alters Phospholipase Trafficking, Inhibits NF-κB Assembly, and Protects Tight Junction Integrity

Authors

John J. Miklavcic, Chapman UniversityFollow
Qun Li, University of Alberta
Jordan Skolnick, Chapman University
Alan B. R. Thomson, Western University
Vera C. Mazurak, University of Alberta
Michael Tom Clandinin, University of Alberta

Document Type

Article

Publication Date

7-5-2021

Abstract

Background and Aims: Dietary gangliosides are present in human milk and consumed in low amounts from organ meats. Clinical and animal studies indicate that dietary gangliosides attenuate signaling processes that are a hallmark of inflammatory bowel disease (IBD). Gangliosides decrease pro-inflammatory markers, improve intestinal permeability, and reduce symptoms characteristic in patients with IBD. The objective of this study was to examine mechanisms by which dietary gangliosides exert beneficial effects on intestinal health.

Methods: Studies were conducted in vitro using CaCo-2 intestinal epithelial cells. Gangliosides were extracted from milk powder and incubated with differentiated CaCo-2 cells after exposure to pro-inflammatory stimuli. Gut barrier integrity was assessed by electron microscopy, epithelial barrier function was examined by measuring transepithelial electric resistance, and content of HBD-2, IL-23, NF-κB, and sPLA₂ was assessed by ELISA.

Results: Ganglioside attenuated the decrease in integrity of tight junctions induced by pro-inflammatory stimuli and improved epithelial barrier function (P < 0.05). Ganglioside decreased the basolateral secretion of sPLA₂ (P ≤ 0.05), lowered HBD-2 and IL-23 levels (P ≤ 0.05), and inhibited NF-κB activation (P ≤ 0.05).

Conclusions: In summary, the present study indicates that ganglioside GD3 improves intestinal integrity by altering sPLA₂ trafficking, and the production of pro-inflammatory mediators is mitigated by decreasing assembly of the NF-κB complex. Dietary gangliosides may have promising potential beneficial effects in IBD as decreased inflammatory signaling, improved intestinal integrity, and maintenance of epithelial barrier function have been demonstrated in vitro.

Comments

This article was originally published in Frontiers in Nutrition, volume 8, in 2021. https://doi.org/10.3389/fnut.2021.705172

Recommended Citation

Miklavcic JJ, Li Q, Skolnick J, Thomson ABR, Mazurak VC, Clandinin MT. Ganglioside Alters Phospholipase Trafficking, Inhibits NF-κB Assembly, and Protects Tight Junction Integrity. Front Nutr. 2021;8:705172. Published 2021 Jul 5. https://doi.org/10.3389/fnut.2021.705172

Peer Reviewed

1

Copyright

The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.