New research continues to add evidence for the influence of microbiota on an organism's health and behavior. Researchers are probing what is known as the microbiota-gut-brain axis, an apparent connection between microbes in the gut and the central nervous system. The communication is thought to be two-way, but elucidating the exact mechanisms is difficult given the myriad microorganisms out there, physiological differences between hosts, and challenges in tracking neuronal signals. Germ-free mice and other gnotobiotic varieties are increasingly under review, but developing alternative models in other species can provide novel opportunities to study the workings of the microbiota-gut-brain axis.
Zebrafish are proving to be popular candidates. Neurobehavioral phenotypes have been documented that correspond well to those established in mice, and they share some characteristics with humans, such as cortisol production under stress, that differ in rodents. Their use in high-throughput screening is also well established, which could speed drug testing if new targets for treating diseases or conditions are identified. In the context of microbial studies, zebrafish are uniquely valuable: they are transparent, enabling internal visualizations if researchers introduce labeled microbes, and they develop from eggs, making it easier to manipulate their innate microbial profiles. A new research article (Behav. Brain Res. 311, 219–227; 2016) and related metagenomic analysis (Data Brief 8, 938–943; 2016) highlight the use of zebrafish in microbial studies.
In particular, the researchers were interested in the relationship between the microbiome and anxiety during early development, the results of which are thought to have lasting effects into adulthood. They examined measures of anxiety in three groups of larval zebrafish: germ-free, which were carefully washed after fertilization with a series of antibiotic, iodine, and bleach solutions before being housed in sterilized water; conventionalized, which underwent the sterilization process but were held in standard fish water; and conventionally raised, receiving no special treatment. Each group had different microbial constituents (with germ-free zebrafish harboring none); despite the differences, conventionalized and conventionally raised fish responded similarly to subsequent tests. Germ-free zebrafish were considerably more carefree than germy ones. They displayed less thigmotaxis, or 'wall-hugging', during an activity assay and did not produce increased cortisol in response to an osmotic stress test. A splash of the probiotic Lactobacillus plantarum, however, calmed anxious behavior in the conventionally raised larvae.
These results demonstrate a link between microbiota and anxiety in zebrafish larvae, as has been previously documented in mice. They also establish zebrafish as a useful alternative model to rodents for consideration in future studies of the microbiota-gut-brain axis.
About this article
Cite this article
Neff, E. Zebrafish as models of microbe-modulated anxiety. Lab Anim 45, 414 (2016). https://doi.org/10.1038/laban.1154