title: Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease.
abstract: OBJECTIVE
  To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease.
  
  
  METHODS
  Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease (n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps (n = 6) and colorectal cancer (n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine (PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A (HEXA) and sialidase-3 (NEU3) were measured in intestinal mucosa using western blot and compared among subject groups.
  
  
  RESULTS
  Relative GM3 ganglioside content was 2-fold higher (P < 0.05) in intestine from patients with inflammatory bowel disease (IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue (P < 0.05). Control intestine exhibited 3-fold higher (P < 0.01) relative GD1a ganglioside content than IBD intestine. GD3 and GD1a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine (P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold (P < 0.05) and NEU3 was increased 8.3-fold (P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1a and PC.
  
  
  CONCLUSIONS
  This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.
authors.affiliation: John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
authors.forename: John J
authors.initials: JJ
authors.lastname: Miklavcic
authors.affiliation: John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
authors.forename: Tasha D L
authors.initials: TD
authors.lastname: Hart
authors.affiliation: John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
authors.forename: Gordon M
authors.initials: GM
authors.lastname: Lees
authors.affiliation: John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
authors.forename: Glen K
authors.initials: GK
authors.lastname: Shoemaker
authors.affiliation: John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
authors.forename: Kareena L
authors.initials: KL
authors.lastname: Schnabl
authors.affiliation: John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
authors.forename: Bodil M K
authors.initials: BM
authors.lastname: Larsen
authors.affiliation: John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
authors.forename: Oliver F
authors.initials: OF
authors.lastname: Bathe
authors.affiliation: John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
authors.forename: Alan B R
authors.initials: AB
authors.lastname: Thomson
authors.affiliation: John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
authors.forename: Vera C
authors.initials: VC
authors.lastname: Mazurak
authors.affiliation: John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
authors.forename: M Tom
authors.initials: MT
authors.lastname: Clandinin
mesh_terms: D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000601:surgery; D003106:Colon / Q000737:chemistry* / Q000601:surgery; D003424:Crohn Disease / Q000378:metabolism* / Q000601:surgery; D005231:Fatty Acids, Unsaturated / Q000032:analysis*; D005679:G(M3) Ganglioside / Q000032:analysis; D005732:Gangliosides / Q000032:analysis*; D006801:Humans; D007082:Ileum / Q000737:chemistry* / Q000601:surgery; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000601:surgery; D009439:Neuraminidase / Q000032:analysis; D010713:Phosphatidylcholines / Q000032:analysis; D010714:Phosphatidylethanolamines / Q000032:analysis; D054820:beta-Hexosaminidase alpha Chain / Q000032:analysis
chemical_list: D005231:Fatty Acids, Unsaturated; D005679:G(M3) Ganglioside; D005732:Gangliosides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C021298:ganglioside, GD1a; C026226:ganglioside, GD3; C465436:Neu3 protein, human; D009439:Neuraminidase; C518253:HEXA protein, human; D054820:beta-Hexosaminidase alpha Chain
keywords: Crohn disease; Fatty acid; Ganglioside; Inflammation; Inflammatory bowel disease; Lipid; Nutrition; Phospholipid; Ulcerative colitis