Short-chain fatty acids are produced by zebrafish microbiota and influence glucose homeostasis

Abstract

Increasingly, attention has been drawn to the association between gut microbiomes and host health, particularly to the production of short-chain fatty acids (SCFA) from indigestible carbohydrates by colonic microbiota. It is known that the main SCFA produced by mammalian intestinal microbiota are acetate, propionate, and butyrate. These SCFA are a significant source of nutrition, providing 10% of a human’s caloric intake, 30% for many herbivores, and up to 70% in ruminants. Additionally, they play a variety of roles in human health: influencing metabolism, inhibiting pathogen growth, and improving nutrient uptake. However, relatively little is known about the production and function of SCFA in non-mammalian vertebrates. One model for studying gut physiology, metabolism, and development is the zebrafish (Danio rerio). The ease of access to transgenic tools and gnotobiotic manipulation, coupled with its establishment as a model system for studying many SCFA-associated physiological outcomes make zebrafish an attractive model system for studying SCFA. However, no studies have tested whether SCFA synthesis occurs in zebrafish intestines. We demonstrate that bacterial communities from adult zebrafish intestines synthesize all three main SCFA in vitro, though no SCFA was detected in zebrafish intestines in vivo. Importantly, we find that treating zebrafish larvae with propionate reduces liver phosphoenolpyruvate carboxykinase 1 expression and overall glucose level, suggesting SCFA production in the intestine may play an important role in regulating glucose homeostasis. These results suggest that zebrafish may serve as an important model to understand the physiological role of SCFA in the context of host-microbe interactions.