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Review
. 2022 Mar 15:544:111554.
doi: 10.1016/j.mce.2022.111554. Epub 2022 Jan 5.

Ceramide signaling in the gut

Ying Li  1 , Rebekah J Nicholson  2 , Scott A Summers  2
Affiliations
Review

Ceramide signaling in the gut

Ying Li et al. Mol Cell Endocrinol. .

Abstract

Sphingolipids are essential lipid components in the intestinal epithelial cells (IEC) along the intestinal tract. They play crucial roles in maintaining barrier integrity, regulating nutrient absorption, and acting as signaling molecules to regulate regeneration and differentiation of intestinal mucosa (Kurek et al., 2012). Ceramide is the central sphingolipid species and the precursor of all complex sphingolipids and other downstream simple intermediates like sphingosine (SPH), ceramide-1-phosphate (C-1-P), and sphingosine-1-phosphate (S-1-P). It is also a critical signaling molecule regulating numerous physiologic and pathologic processes. This review will summarize the metabolism of ceramides in the gut and their regulation in inflammatory bowel diseases and colorectal cancer.

Keywords: Ceramide; Colon cancer; Inflammatory bowel disease; Intestine; NAFLD.

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Conflict of interest statement

Declaration of competing interest

SAS is a founder and shareholder with Centaurus Therapeutics.

Figures

Figure. 1
Figure. 1
Ceramide production pathways in the intestinal epithelium. Schematic depiction of the major pathways controlling ceramide levels in the intestinal epithelial cells: de novo synthesis, hydrolysis of complex sphingolipids (for example, sphingomyelin hydrolysis) and the salvage pathway. SPT, serine palmitoyltransferase; 3KSR, 3-ketosphinganine reductase; CERS, ceramide synthase; DES1, dihydroceramide desaturase 1; aCDase, acid ceramidase; nCDase, neutral ceramidase; aSMase, acid sphingomyelinase; nSMase, neutral sphingomyelinase; alk-SMase, alkaline sphingomyelinase; SMS, sphingomyelin synthase; TAG, triacylglyceride.
Figure 2.
Figure 2.. Ceramide in microbiome-gut-liver axis.
(Left) Inhibition of sphingolipid de novo synthesis pathway decreases ceramides level and leads to barrier dysfunction in the IEC. Bacteria and their metabolites infiltration in the IEC cause chronic inflammation and increase the risk of NAFLD and NASH. (Right) Schematic depiction of the role ceramides played in two pathways that microbiome regulates the metabolites in the gut lumen and causes liver steatosis and NASH. LPS, lipopolysaccharide; TCA, taurocholic acid; SCFA, short-chain fatty acid; FXR, farnesoid X receptor; HIF2α, hypoxia-inducible factor 2α; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis.
See this image and copyright information in PMC

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