Journal Article

Prenatal Methyl-Donor Supplementation Augments Colitis in Young Adult Mice

Nagy-Szakal, Dorottya, Dowd, Scot E., Mir, Sabina A., Kellermayer, Richard, Smith, C. Wayne, Szigeti, Reka G.

2013

Overview

Inflammatory bowel diseases (IBD) have become highly prevalent in developed countries. Environmentally triggered exaggerated immune responses against the intestinal microbiome are thought to mediate the disorders. The potential dietary origins of the disease group have been implicated. However, the effects of environmental influences on prenatal developmental programming in respect to orchestrating postnatal microbiome composition and predilection towards mammalian colitis have not been examined. We tested how transient prenatal exposure to methyl donor micronutrient (MD) supplemented diets may impact predilection towards IBD in a murine dextran sulfate sodium (DSS) colitis model. Prenatal MD supplementation was sufficient to modulate colonic mucosal Ppara expression (3.2 fold increase; p=0.022) and worsen DSS colitis in young adulthood. The prenatal dietary exposure shifted the postnatal colonic mucosal and cecal content microbiomes. Transfer of the gut microbiome from prenatally MD supplemented young adult animals into germ free mice resulted in increased colitis susceptibility in the recipients compared to controls. Therefore, the prenatal dietary intervention induced the postnatal nurturing of a colitogenic microbiome. Our results show that prenatal nutritional programming can modulate the mammalian host to harbor a colitogenic microbiome. These findings may be relevant for the nutritional developmental origins of IBD.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aging / Agriculture / Animals / Animals, Newborn / Bacteria / Cecum / Colitis / Colitis - chemically induced / Colitis - microbiology / Colitis - pathology / Deoxyribonucleic acid / Developed countries / Dextran / Dextran sulfate / Diet / Dietary supplements / Dietary Supplements - adverse effects / Disease / DNA / DNA methylation / Environmental effects / Epigenetics / Exposure / Farms / Feces - microbiology / Female / Gastroenterology / Gene expression / Hepatology / Hospitals / Hypotheses / Immune response / Inflammatory bowel disease / Inflammatory bowel diseases / Intestinal microflora / Intestinal Mucosa - microbiology / Intestinal Mucosa - pathology / Intestine / Laboratory animals / Male / Mammals / Medical research / Medicine / Methylation / Mice, Inbred C57BL / Microbiota / Mortality / Mucosa / Nutrition research / Origins / Pediatrics / PPAR alpha - metabolism / Pregnancy / Prenatal experience / Prenatal exposure / Prenatal Exposure Delayed Effects - pathology / Sodium / Sulfates / Vitamin B