title: Methyl deficient diet aggravates experimental colitis in rats.
abstract: Inflammatory bowel diseases (IBD) result from complex interactions between environmental and genetic factors. Low blood levels of vitamin B12 and folate and genetic variants of related target enzymes are associated with IBD risk, in population studies. To investigate the underlying mechanisms, we evaluated the effects of a methyl-deficient diet (MDD, folate, vitamin B12 and choline) in an experimental model of colitis induced by dextran sodium sulphate (DSS), in rat pups from dams subjected to the MDD during gestation and lactation. Four groups were considered (n = 12-16 per group): C DSS(-) (control/DSS(-)), D DSS(-) (deficient/DSS(-)), C DSS(+) (control/DSS(+)) and D DSS(+) (deficient/DSS(+)). Changes in apoptosis, oxidant stress and pro-inflammatory pathways were studied within colonic mucosa. In rat pups, the MDD produced a decreased plasma concentration of vitamin B12 and folate and an increased homocysteine (7.8 ± 0.9 versus 22.6 ± 1.2 μmol/l, P < 0.001). The DSS-induced colitis was dramatically more severe in the D DSS(+) group compared with each other group, with no change in superoxide dismutase and glutathione peroxidase activity, but decreased expression of caspase-3 and Bax, and increased Bcl-2 levels. The mRNA levels of tumour necrosis factor (TNF)-α and protein levels of p38, cytosolic phospolipase A2 and cyclooxygenase 2 were significantly increased in the D DSS(+) pups and were accompanied by a decrease in the protein level of tissue inhibitor of metalloproteinases (TIMP)3, a negative regulator of TNF-α. MDD may cause an overexpression of pro-inflammatory pathways, indicating an aggravating effect of folate and/or vitamin B12 deficiency in experimental IBD. These findings suggest paying attention to vitamin B12 and folate deficits, frequently reported in IBD patients.
authors.affiliation: Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.forename: Amandine
authors.initials: A
authors.lastname: George
authors.forename: Florence
authors.initials: F
authors.lastname: Coste
authors.forename: Aude
authors.initials: A
authors.lastname: Bressenot
authors.forename: Carine
authors.initials: C
authors.lastname: Bossenmeyer-Pourie
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Alberto
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: Bernard
authors.initials: B
authors.lastname: Namour
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis; D002796:Choline Deficiency; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016264:Dextran Sulfate / Q000494:pharmacology; D004032:Diet; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency; D005979:Glutathione Peroxidase / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D054467:Phospholipases A2 / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014805:Vitamin B 12 / Q000097:blood; D014806:Vitamin B 12 Deficiency; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D006710:Homocysteine; D016264:Dextran Sulfate; D005492:Folic Acid; D005979:Glutathione Peroxidase; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; D054467:Phospholipases A2; D053148:Caspase 3; D014805:Vitamin B 12