Tributyltin exposure leads to increased adiposity and reduced abundance of leptogenic bacteria in the zebrafish intestine

Abstract

The chemical obesogen tributyltin (TBT) is known to promote fat storage in adipose tissue through direct action on vertebrate cells. TBT also has direct toxic effects on microorganisms, raising the possibility that TBT may also promote fat storage in vertebrates by altering their microbiota. Here we show that exposure of conventionally-reared post-embryonic zebrafish to TBT results in increased adiposity, reduced body size, and altered intestinal microbiota composition including reduced relative abundance of Plesiomonas bacteria. To test if those microbiota alterations affected host adiposity, we exposed conventionally-reared zebrafish to intestinal bacterial strains representative of TBT-altered taxa. We found that introduction of a Plesiomonas strain into conventionally-reared zebrafish was sufficient to reduce adiposity and alter intestinal microbiota composition. Using new long-term gnotobiotic zebrafish husbandry methods, we found that colonization of germ-free zebrafish with Plesiomonas was sufficient to reduce host adiposity. Together these results show the leptogenic activity of Plesiomonas on zebrafish hosts, indicating that the ability of TBT to increase adiposity in vivo may be due in part to TBT-mediated modification of the abundance of leptogenic bacteria like Plesiomonas. These findings underscore how complex reciprocal interactions between animals and their microbial and chemical environments can influence energy balance and metabolic health.IMPORTANCEObesogens are environmental chemicals that promote fat storage and are generally thought to exert this effect directly on animal cells. Using zebrafish, we show that the obesogen tributyltin can also promote fat storage by acting upon intestinal microbiota via reduction of bacteria that are sufficient to reduce fat storage.

Using zebrafish to understand reciprocal interactions between the nervous and immune systems and the microbial world

“…The zebrafish is a powerful system to test such issues, at least in early development, because of the ease and limited costs of generating axenic (also called germ-free) larvae, which can be recolonized in a controlled way [ 21 ]. These axenic or gnotobiotic larvae can then be fed with sterile chow or axenic live foods to be grown for several weeks to juvenile stage, or months to adulthood, although this becomes labor-intensive [ 22 , 23 ]. Thus, most behavioral assays on gnotobiotic zebrafish are conducted at the larval stage.…”