337 - Butyrate supplementation during pregnancy reduces neonatal gut injury in a murine intestinal inflammation model

Poster Number: 337
Publication Number: 337.133

Maria E. Barbian, Emory University School of Medicine, Decatur, GA, United States; Crystal Naudin, Emory University School of Medicine, Atlanta, GA, United States; Patricia W. Denning, Emory University School of Medicine, Atlanta, GA, United States; Ravi M. Patel, Children's Healthcare of Atlanta and Emory University, Atlanta, GA, United States; Subra Kugathasan, Emory University, Atlanta, GA, United States; Rheinallt Jones, Emory University School of Medicine, Atlanta, GA, United States

Background: The diet during pregnancy (antenatal diet) impacts fetal gut development. Butyrate is a short-chain fatty acid (SCFA), generated by gut bacteria, which dampens intestinal inflammation in part through upregulation of TGF-beta and down regulation of NF-kappa B. Previously, we demonstrated that butyrate supplementation during pregnancy in mice protects adult offspring from experimentally induced colitis.

Objective: In this study, we evaluated whether butyrate supplementation during pregnancy protects offspring against a murine model of neonatal intestinal injury. We hypothesize that butyrate supplementation during pregnancy increases fetal exposure to butyrate, protecting against neonatal gut injury via down regulation of intestinal inflammation.

Design/Methods: Mating pairs of C57BL/6 mice were assigned to an experimental or a control group. The experimental group received 1% butyrate in their drinking water throughout their pregnancy. Two-week-old pups were subjected to intestinal inflammation through an established gut inflammation and injury model with intraperitoneal injection of lipopolysaccharide and platelet activating factor and four hours later, were euthanized. Intestinal injury was measured in blinded fashion through histopathologic scoring. Samples of ileum were obtained for gene enrichment analysis. Colonic tissue and stool samples were collected for SCFA analysis. 
 

 

Results:

The histopathologic analysis revealed pups from the antenatal butyrate group, born to dams who received butyrate during pregnancy, have significantly lower injury scores than control pups (p-value: 0.02). Through RT-qPCR from ileum tissue samples, pups from the antenatal butyrate group had 3.5-times higher levels of TGF-beta 1 mRNA expression (p-value: 0.02) and 90-times lower levels of NF-kappa B expression (p-value: 0.04). Butyrate levels from colonic tissue of pups were evaluated and the preliminary results suggest that butyrate levels are not significantly different between the two groups. Butyrate levels from stool of pups are pending. 


Conclusion(s): Butyrate supplementation in pregnancy resulted in protection against neonatal intestinal injury among 2-week-old murine offspring. This may be secondary to decreased inflammatory tone in the gut of the offspring exposed to butyrate during fetal development as increased TGF-beta signaling dampens inflammation. There was no difference in butyrate levels within colonic tissue of 2-week-old pups, this may be due to rapid utilization of butyrate by colonic tissue. Our results highlight the powerful influence of the diet during pregnancy on gut development and future gut health.