599 - The impact of butyrate on Group B Streptococcus intestinal pathogenesis

Poster Number: 599
Publication Number: 599.411

Background: Group B Streptococcus (Streptococcus agalactiae; GBS) is a leading cause of neonatal sepsis worldwide. GBS is a pathobiont of the intestinal tract capable of translocating via the paracellular and transcellular routes leading to invasive disease. Neonatal susceptibility to invasive disease stems from immature intestinal barriers. We have previously shown that GBS intestinal colonization induces major transcriptomic changes in the colonic epithelium, specifically pertaining to intestinal barrier function and immune regulation. Butyrate, a microbial metabolite produced by fermentation of dietary fiber, bolsters intestinal barrier function and immune responses to enteric pathogens. Furthermore, maternal diet primes the neonatal intestinal environment and, more specifically, maternal butyrate treatment (mButyrate) fortifies intestinal barrier integrity in offspring.

Objective: Our aim was to determine the impact of butyrate on GBS and the intestinal epithelial barrier. We postulated that mButyrate would decrease GBS colonization and invasion via enhanced intestinal barrier function.

Design/Methods: We used GBS COH-1 serotype III ST-17 in all experiments. First, we used human intestinal epithelial cells (IEC) lines (CACO-2, T-84) to evaluate the impact of butyrate on GBS-induced cell death, GBS adhesion and invasion of IEC, and epithelial monolayer permeability. Then, we used an established mouse model of post-natal GBS acquisition to evaluate the effects of mButyrate on offspring. Briefly, pregnant dams were treated with butyrate in their drinking water [150mM] throughout pregnancy and weaning and compared to untreated dams. mButyrate (n=12) and control (n=9) pups were orally gavaged with GBS on postnatal day 10. Intestines were harvested on postnatal day 14 and processed for determination of bacterial burden. Weights were recorded 3 times weekly.

Results: In IEC, we found that butyrate significantly restores cell viability (Figure 1), reduces GBS invasion, and decreases monolayer permeability (Figure 2). mButyrate pups had decreased GBS burden in the small intestine (Figure 3) and restored weight gain post-infection.

Conclusion(s): Based on our results, butyrate offsets adverse effects of GBS in vitro and has the potential to be used as an antenatal strategy to mitigate neonatal sepsis risk.