Abstract 088: Modulatory Effects Of The Gut Microbiota-derived Short Chain Fatty Acids On Heart Rate And Vascular Tone In Larval Zebrafish

Abstract

Introduction: Short chain fatty acids (SCFAs), such as acetic, propionic, and butyric acid, areproduced by fermentation of dietary fibers by the gut bacteria. Deregulation in production andhandling of SCFAs is associated with cardiovascular dysfunction in humans and rodents.However, limited studies have investigated the effect of SCFAs on cardiovascular parameters inthe zebrafish (ZF), an increasingly popular model in cardiovascular and gut microbiota research. Methods: Bacterial 16s sequencing and GC-MS were performed in adult male and female Tg(NFkB:EGFP) ZF fecal samples for analysis of the gut microbiota and SCFAs respectively. Inanaesthetized ZF larvae (7-9 dpf; MS-222, 0.3mM), measurements of heart rate (HR, bpm) andvascular tone (width of dorsal aorta, pixels) were performed every 10 minutes for an hour usinglive imaging (Nikon, 4x magnification) following administration of physiologic concentrations ofacetate (27.4 μM), butyrate (2.2 μM) and propionate (1.7 μM; pH=7.5) via immersion. Results: Relative proportions of SCFAs in the ZF were similar to those previously reported in rats andhumans, with highest levels of acetic acid (27.43 μM) followed by butyric (2.19 μM) and propionic(1.65 μM) acid. At the phylum level, the observed abundances of Proteobacteria, Firmicutes, andFusobacteria were similar to those reported in rodents and humans. Administration of selectSCFAs resulted in a ~20% decrease in HR at all time points following administration of butyrate(P<0.0001), and at 40-60min following administration of acetate (P<0.05), with no effect ofpropionate. In addition, a ~25% decrease in the width of the dorsal aorta was observed at 60 minfollowing administration of butyrate (P<0.05), with no effect of acetate or propionate. Conclusion: We report a similar composition and abundances of the gut microbiota and SCFAs between ZF,rodents and humans. In addition, both butyrate and acetate produced a bradycardia in the ZF,while the observed butyrate-dependent decrease in the vascular tone may be compensatory tobradycardia. Our findings demonstrate the potential for ZF as a model to study host-microbiotainteractions in regulation of cardiovascular function.