Metabolism of sphingolipids in the gut and its relation to inflammation and cancer development

Abstract

Sphingolipids are abundant in the microvillar membrane of intestinal epithelial cells where they are essential for structural integrity and may act as receptors for toxins, virus and bacteria. Metabolism of dietary and membrane sphingolipids in the intestine generates ceramide, sphingosine, sphingosine-1-phosphate, and ceramide-1-phosphate, via the action of alkaline sphingomyelinase, neutral ceramidase, sphingosine-1-kinase, and ceramide-1-kinase. These intermediary metabolites act as bioactive lipid messengers, influencing numerous cellular functions including growth, differentiation and apoptosis of both epithelial and immunocompetent cells in the gastrointestinal tract, and also the progress of inflammation and responsiveness of the mucosal cells to pathogens. This review summarizes background and recent progress in the metabolism of dietary and endogenous sphingolipids in the gut and its pathophysiological implications.

Effects of Dietary Plant-Origin Glucosylceramide on Bowel Inflammation in DSS-Treated Mice

“…Sphingoid bases hydrolyzed from complex sphingolipid or de novo synthesis are converted to sphingosine-1-phosphate, which then accelerate inflammatory reaction via sphingosine-1-phosphate receptors 10,28 .…”

Potential health benefits of sphingolipids in milk and dairy products

“…Most research is centered on some cancers and neurological pathologies. Ceramides and sphingosine, the digestion products of sphingolipids, affect cell growth, differentiation and apoptosis, suggesting that their release may affect the behavior of normal or transformed cells, especially in the intestine (Duan and Nilsson, 2009). Dietary sphingolipids may be the key link connecting diet, inflammation and cancer (Canela et al, 2016).…”

Nutraceutical Properties of Milk Fat Globular Membrane

“…As a consequence, many dietary treatments have been tested specifically for their ability to inhibit colon cancer. Previous studies have demonstrated that purified sphingolipids, such as sphingomyelin, are protective against colon cancer in animal models (Duan and Nilsson 2009;El Alwani et al 2006). Sphingolipids are composed of a ceramide core, which in turn, is composed of a sphingosine backbone with a fatty acid covalently bonded via an amide linkage.…”

“…While the mechanism of how gut barrier dysfunction occurs is unclear, pro-inflammatory cytokines, such as, IL-4, IL-13, IFN-, and TNF-α, have been reported to increase the permeability of intestinal epithelia (Fink 2003;Lewis and McKay 2009;Yajima et al 2009). Several studies suggest that various milk sphingolipids, including sphingomyelin and gangliosides, positively affect the gut by exhibiting a protective effect against colon cancer (Dillehay et al 1994;Duan and Nilsson 2009;Nilsson and Duan 2006;Schmelz et al 1996;Schmelz et al 2000), and other studies have linked sphingolipids and other milk fat fractions containing phospholipids and gangliosides to the inhibition of a pro-inflammatory response and gut barrier protection (Dalbeth et al 2009;El Alwani et al 2006;Park et al 2007;Park et al 2005;. One source of a variety of dietary sphingolipids is MFGM.…”