• Open Access

Methyl deficient diet aggravates experimental colitis in rats

Authors

  • Min Chen,

    1. Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France
    2. Department of Gastroenterology, Zhongnan Hospital, Hubei Provincial Center for Clinical Study of Intestinal Diseases, the Key Laboratory of Allergy and Immune-related Diseases, Wuhan University School of Medicine, Wuhan, China
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    • These authors contributed equally.

  • Laurent Peyrin-Biroulet,

    1. Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France
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    • These authors contributed equally.

  • Amandine George,

    1. Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France
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  • Florence Coste,

    1. Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France
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  • Aude Bressenot,

    1. Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France
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  • Carine Bossenmeyer-Pourie,

    1. Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France
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  • Jean-Marc Alberto,

    1. Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France
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  • Bing Xia,

    1. Department of Gastroenterology, Zhongnan Hospital, Hubei Provincial Center for Clinical Study of Intestinal Diseases, the Key Laboratory of Allergy and Immune-related Diseases, Wuhan University School of Medicine, Wuhan, China
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  • Bernard Namour,

    1. Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France
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  • Jean-Louis Guéant

    Corresponding author
    1. Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France
      Prof. Jean-Louis GUÉANT, Inserm U-954, Nutrition-Genetics-Environment, Faculté de Médecine, 9 avenue de la Forêt de Haye, B.P. 184, 54500, Nancy-Vandœuvre, France. Tel.: +(33) 3 83 68 39 92 Fax: +(33) 3 83 68 32 79 E-mail: jean-louis.gueant@medecine.uhp-nancy.fr
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Prof. Jean-Louis GUÉANT, Inserm U-954, Nutrition-Genetics-Environment, Faculté de Médecine, 9 avenue de la Forêt de Haye, B.P. 184, 54500, Nancy-Vandœuvre, France. Tel.: +(33) 3 83 68 39 92 Fax: +(33) 3 83 68 32 79 E-mail: jean-louis.gueant@medecine.uhp-nancy.fr

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.

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