Author
MIR, SABINA - Baylor College Of Medicine | |
NAGY-SZAKAL, DOROTTYA - Baylor College Of Medicine | |
DOWD, SCOT - Molecular Research Lp (MR DNA) | |
SZIGETI, REKA - Baylor College Of Medicine | |
SMITH, CLIFTON - Children'S Nutrition Research Center (CNRC) | |
KELLERMAYER, RICHARD - Baylor College Of Medicine |
Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 7/17/2013 Publication Date: 8/10/2013 Citation: Mir, S.R., Nagy-Szakal, D., Dowd, S.E., Szigeti, R.G., Smith, C.W., Kellermayer, R. 2013. Prenatal methyl-donor supplementation augments colitis in young adult mice. PLoS One. 8(8):e73162. Interpretive Summary: Inflammatory bowel diseases have become highly prevalent in developed countries. We tested in mice if maternal exposure to diets containing micronutrients known to influence some gene expression will influence the occurrence of inflammatory bowel disease in the offspring. Our results showed that this dietary exposure during pregnancy increased the severity of bowel inflammation in the young adult offspring and changed the normal balance of bacteria in the bowel in a way that promoted bowel inflammation. These findings may be relevant for the nutritional developmental origins of inflammatory bowel diseases. Technical Abstract: Inflammatory bowel diseases 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 supplemented diets may impact predilection towards inflammatory bowel diseases in a murine dextran sulfate sodium colitis model. Prenatal methyl donor micronutrient supplementation was sufficient to modulate colonic mucosal Ppara expression and worsen dextran sulfate sodium colitis in young adulthood. The prenatal dietary exposure shifted the postnatal colonic mucosal and cecal content microbiomes. Transfer of the gut microbiome from prenatally methyl donor micronutrient 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 inflammatory bowel diseases. |