Transplantation of high fat fed mouse microbiota into zebrafish larvae identifies MyD88-dependent acceleration of hyperlipidaemia by Gram positive cell wall components

Abstract

Gut dysbiosis is an important modifier of pathologies including cardiovascular disease but our understanding of the role of individual microbes is limited. Here, we have used transplantation of mouse microbiota into microbiota-deficient zebrafish embryos to study the interaction between members of a mammalian high fat diet-associated gut microbiota with a lipid rich diet challenge in a tractable model species. We find zebrafish embryos are more susceptible to hyperlipidaemia when colonised with mouse high fat-diet-associated microbiota and that this effect can be driven by individual bacterial species. Colonisation or exposure to Enterococcus faecalis activates host Myd88 signalling, an effect that is phenocopied by the Gram positive Toll-like receptor agonists peptidoglycan and lipoteichoic acid, to drive hyperlipidaemia. In contrast, we find Stenotrophomonas maltophilia increases the hyperlipidaemic potential of chicken egg yolk independent of gut colonisation. In this work, we demonstrate the applicability of zebrafish as a tractable host for the identification of gut pathobionts via microbiota transplantation and subsequent challenge with a high fat diet.

Exposure to the gut microbiota from cigarette smoke-exposed mice exacerbates cigarette smoke extract-induced inflammation in zebrafish larvae

“…Our system of using a sub-optimal dose of 1% CSE for two days to stimulate a below measurable amount of inflammation proved sensitive to positive modulation by microbiota samples from CS-exposed mouse faeces. Zebrafish have been used to as hosts for trans-species microbiota transplants ( Rawls et al, 2006 ; Cholan et al, 2021 ), and our study expands this knowledge by demonstrating sensitivity of recipient zebrafish host inflammation to a microbiota-environment interaction. These proof-of-concept data suggest that zebrafish larvae may be a feasible platform with which human microbiota-CS interactions can be screened to uncover potential missing links in microbiota-environment interactions that appear to predispose some smokers to the development of COPD ( Budden et al, 2017 , 2019 ; Bowerman et al, 2020 ).…”

Transplantation of high fat fed mouse microbiota into zebrafish larvae identifies MyD88‐dependent acceleration of hyperlipidaemia by Gram‐positive cell wall components

“…Knockdown efficacy was monitored by RT-qPCR as previously described. 35 myd88-specific primers (5 0 -3 0 ): Fw ACAGGGACTGACACCTGAGA, Rv GACGACAGG GATTAGCCGTT.…”