Butyrate Supplementation to Pregnant Mice Elicits Cytoprotection Against Colonic Injury in Offspring

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 which 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 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 to eight-week-old offspring were subjected to dextran sulfate sodium-induced colitis. Fecal microbiome analysis was performed on 6 to 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 specific gut microbes. CONCLUSIONS: Antenatal butyrate supplementation resulted in down regulation 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 offspring.