Methyl donor deficiency affects small-intestinal differentiation and barrier function in rats.
Dietary methyl donors and their genetic determinants are associated with Crohn's disease risk. We investigated whether a methyl-deficient diet (MDD) may affect development and functions of the small intestine in rat pups from dams subjected to the MDD during gestation and lactation. At 1 month before pregnancy, adult females were fed with either a standard food or a diet without vitamin B12, folate and choline. A global wall hypotrophy was observed in the distal small bowel (MDD animals 0·30 mm v. controls 0·58 mm; P< 0·001) with increased crypt apoptosis (3·37 v. 0·4%; P< 0·001), loss of enterocyte differentiation in the villus and a reduction in intestinal alkaline phosphatase production. Cleaved caspase-3 immunostaining (MDD animals 3·37% v. controls 0·4%, P< 0·001) and the Apostain labelling index showed increased crypt apoptosis (3·5 v. 1·4%; P= 0·018). Decreased proliferation was observed in crypts of the proximal small bowel with a reduced number of minichromosome maintenance 6 (MDD animals 52·83% v. controls 83·17%; P= 0·048) and proliferating cell nuclear antigen-positive cells (46·25 v. 59 %; P= 0·05). This lack of enterocyte differentiation in the distal small bowel was associated with an impaired expression of β-catenin and a decreased β-catenin-E-cadherin interaction. The MDD affected the intestinal barrier in the proximal small bowel by decreasing Paneth cell number after immunostaining for lysosyme (MDD animals 8·66% v. controls 21·66%) and by reducing goblet cell number and mucus production after immunostaining for mucin-2 (crypts 8·66 v. 15·33%; villus 7 v. 17%). The MDD has dual effects on the small intestine by producing dramatic effects on enterocyte differentiation and barrier function in rats.
Inserm U-954, Molecular and Cellular Pathology in Nutrition, Faculté de Médecine, CHU Nancy, Nancy-Université, 9 avenue de la Forêt de Haye, BP 184, Nancy, 54500 Vandoeuvre, France.
Aude
A
Bressenot
Inserm U-954, Molecular and Cellular Pathology in Nutrition, Faculté de Médecine, CHU Nancy, Nancy-Université, 9 avenue de la Forêt de Haye, BP 184, Nancy, 54500 Vandoeuvre, France.
Shabnam
S
Pooya
Inserm U-954, Molecular and Cellular Pathology in Nutrition, Faculté de Médecine, CHU Nancy, Nancy-Université, 9 avenue de la Forêt de Haye, BP 184, Nancy, 54500 Vandoeuvre, France.
Carine
C
Bossenmeyer-Pourie
Inserm U-954, Molecular and Cellular Pathology in Nutrition, Faculté de Médecine, CHU Nancy, Nancy-Université, 9 avenue de la Forêt de Haye, BP 184, Nancy, 54500 Vandoeuvre, France.
Guillaume
G
Gauchotte
Inserm U-954, Molecular and Cellular Pathology in Nutrition, Faculté de Médecine, CHU Nancy, Nancy-Université, 9 avenue de la Forêt de Haye, BP 184, Nancy, 54500 Vandoeuvre, France.
Adeline
A
Germain
Inserm U-954, Molecular and Cellular Pathology in Nutrition, Faculté de Médecine, CHU Nancy, Nancy-Université, 9 avenue de la Forêt de Haye, BP 184, Nancy, 54500 Vandoeuvre, France.
Jean-Baptiste
JB
Chevaux
Inserm U-954, Molecular and Cellular Pathology in Nutrition, Faculté de Médecine, CHU Nancy, Nancy-Université, 9 avenue de la Forêt de Haye, BP 184, Nancy, 54500 Vandoeuvre, France.
Florence
F
Coste
Inserm U-954, Molecular and Cellular Pathology in Nutrition, Faculté de Médecine, CHU Nancy, Nancy-Université, 9 avenue de la Forêt de Haye, BP 184, Nancy, 54500 Vandoeuvre, France.
Jean-Michel
JM
Vignaud
Inserm U-954, Molecular and Cellular Pathology in Nutrition, Faculté de Médecine, CHU Nancy, Nancy-Université, 9 avenue de la Forêt de Haye, BP 184, Nancy, 54500 Vandoeuvre, France.
Jean-Louis
JL
Guéant
Inserm U-954, Molecular and Cellular Pathology in Nutrition, Faculté de Médecine, CHU Nancy, Nancy-Université, 9 avenue de la Forêt de Haye, BP 184, Nancy, 54500 Vandoeuvre, France.
Laurent
L
Peyrin-Biroulet
D000469:Alkaline Phosphatase / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D002794:Choline / Q000378:metabolism; D002796:Choline Deficiency / Q000378:metabolism*; D020895:Enterocytes / Q000166:cytology*; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000378:metabolism*; D005786:Gene Expression Regulation; D007421:Intestine, Small / Q000473:pathology*; D009113:Muramidase / Q000378:metabolism; D019879:Paneth Cells / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014805:Vitamin B 12 / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D051176:beta Catenin; D005492:Folic Acid; D000469:Alkaline Phosphatase; D009113:Muramidase; D053148:Caspase 3; D002794:Choline; D014805:Vitamin B 12