Chronotropic and vasoactive properties of the gut bacterial short chain fatty acids in larval zebrafish.

Short-chain fatty acids (SCFAs) by the gut bacteria have been associated with cardiovascular dysfunction in humans and rodents. However, studies exploring effects of SCFAs on cardiovascular parameters in the zebrafish, an increasingly popular model in cardiovascular research, remain limited. Here, we performed fecal bacterial 16S sequencing and gas chromatography/mass spectrometry (GC-MS) to determine the composition and abundances of gut microbiota and SCFAs in adult zebrafish. Following this, the acute effects of major SCFAs on heart rate and vascular tone were measured in anaesthetized zebrafish larvae using fecal concentrations of butyrate, acetate, and propionate. Lastly, we investigated if co-incubation with butyrate may lessen the effects of angiotensin II (Ang II) and phenylephrine (PE) on vascular tone in anaesthetized zebrafish larvae. We found that the abundance in Proteobacteria , Firmicutes , and Fusobacteria phyla in the adult zebrafish resembled those reported in rodents and humans. SCFA levels with highest concentration of acetate (27.43µM), followed by butyrate (2.19µM) and propionate (1.65µM) were observed in the fecal samples of adult zebrafish. Immersion in butyrate and acetate produced a ~20% decrease in heart rate (HR), respectively, with no observed effects of propionate. Butyrate alone also produced a ~25% decrease in the cross-sectional width of the dorsal aorta (DA) at 60 min (* P<0.05), suggesting compensatory vasoconstriction, with no effects of either acetate or propionate. In addition, butyrate significantly alleviated the decrease in DA cross-sectional width produced by both Ang II and PE. We demonstrate the potential for zebrafish in investigation of host-microbiota interactions in cardiovascular health.