Butyrate supplementation to pregnant mice elicits cytoprotection against colonic injury in the offspring

• Type of Material: Article
• Authors: Maria Barbian, Emory University; Joshua A. Owens, Emory University; Crystal R. Naudin, Emory University; Patricia Denning, Emory University; Ravi Patel, Emory University; Rheinallt Jones, Emory University
• Language: English
• Date: 2021-10-06
• Publisher: SPRINGERNATURE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use
• Final Published Version (URL): http://dx.doi.org/10.1038/s41390-021-01767-1
• Title of Journal or Parent Work: PEDIATRIC RESEARCH
• Volume: 92
• Issue: 1
• Start Page: 125
• End Page: 134
• Grant/Funding Information: The Emory Integrated Core Facilities are supported by the Emory Neuroscience NINDS Core Facilities, the Georgia Clinical & Translational Science Alliance, and the Emory University School of Medicine.; MEB is supported in part by American Academy of Pediatrics Marshall Klaus Neonatal-Perinatal Research Award and Emory University Department of Pediatrics and Children’s Healthcare of Atlanta Warshaw Fellow’s Research Award. JAO is supported by the NIH through F31CA247415. CRN is supported by an American Heart Association fellowship 19POST34370006. PD is supported by NIH through 5P01HL086773. RMP is supported by NIH through K23HL128942. RMJ is supported, in part, by NIH Grant R01DK098391 and R01CA179424
• Keywords: CHAIN FATTY-ACIDS; INFLAMMATION; Life Sciences & Biomedicine; SUSCEPTIBILITY; Pediatrics; Science & Technology; MOUSE; FERMENTATION; GUT MICROBIOTA; COLITIS
• Research Categories: Health Sciences, Obstetrics and Gynecology; Biology, Molecular

Abstract

Background: Maternal diet during pregnancy can impact progeny health and disease by influencing the offspring’s gut microbiome and immune development. Gut microbial metabolism generates butyrate, a short-chain fatty acid that benefits intestinal health. Here we assess the effects of antenatal butyrate on the offspring’s gastrointestinal health. We hypothesized that antenatal butyrate supplementation will induce protection against colitis in the offspring. Methods: C57BL/6 mice received butyrate during pregnancy and a series of experiments were performed on their offspring. RNA sequencing was performed on colonic tissue of 3-week-old offspring. Six–8-week-old offspring were subjected to dextran sulfate sodium-induced colitis. Fecal microbiome analysis was performed on the 6–8-week-old offspring. Results: Antenatal butyrate supplementation dampened transcript enrichment of inflammation-associated colonic genes and prevented colonic injury in the offspring. Antenatal butyrate increased the offspring’s stool microbiome diversity and expanded the prevalence of specific gut microbes. Conclusions: Antenatal butyrate supplementation resulted in downregulation of genes in the offspring’s colon that function in inflammatory signaling. In addition, antenatal butyrate supplementation was associated with protection against colitis and an expanded fecal microbiome taxonomic diversity in the offspring. Impact: Dietary butyrate supplementation to pregnant mice led to downregulation of colonic genes involved in inflammatory signaling and cholesterol synthesis, changes in the fecal microbiome composition of the offspring, and protection against experimentally induced colitis in the offspring.These data support the mounting evidence that the maternal diet during pregnancy has enduring effects on the offspring’s long-term health and disease risk.Although further investigations are needed to identify the mechanism of butyrate’s effects on fetal gut development, the current study substantiates the approach of dietary intervention during pregnancy to optimize the long-term gastrointestinal health of the offspring.