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

John J Miklavcic; Qun Li; Jordan Skolnick; Alan B R Thomson; Vera C Mazurak; Micheal Tom Clandinin

doi:10.3389/fnut.2021.705172

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

Front Nutr. 2021 Jul 5:8:705172. doi: 10.3389/fnut.2021.705172. eCollection 2021.

Authors

John J Miklavcic^{1

2}, Qun Li³, Jordan Skolnick¹, Alan B R Thomson⁴, Vera C Mazurak³, Micheal Tom Clandinin^{3

5}

Affiliations

¹ Schmid College of Science and Technology, Chapman University, Orange, CA, United States.
² School of Pharmacy, Chapman University, Irvine, CA, United States.
³ Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB, Canada.
⁴ Division of Gastroenterology, Western University, London, ON, Canada.
⁵ Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada.

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.

Keywords: crohn; immunology; inflammation; inflammatory bowel disease; intestinal permeability; nutrition; sphingolipid; ulcerative colitis.