Microbial indole signaling through AhR facilitates learning and memory behaviors in honeybees

2022 May Highlight

Microbial indole signaling through AhR facilitates learning and memory behaviors in honeybees

Germ-free mice have offered a model to investigate the roles that the gut microbiota play during development and disease. It is appreciated that the commensal microbes help to educate the immune system and without their presence the immune system is under developed. Furthermore, gut microbes contribute to the hosts metabolism. For example, microbes generate indolic compounds from tryptophan and these microbial-derived metabolites have been shown to be either protective or risk-factors for type 2 diabetes, as was shown in our feature article in September 2021. With the gut-brain axis these metabolites can also impact the brain.

As such, a recent study published by Dr. Zijing Zhang et al. in Nature Communications investigated the impact that the gut microbiota has on leaning and memory behaviors in honeybees. An olfactory learning test was used to determine the impact gut microbes have on memory. Antibiotic-treated honeybees had a reduction in the number of successful tests however, microbe-free bees were unable to pass the test suggesting that the gut microbiome affects learning and memory. This was further supported by striking transcriptional changes between the groups. Microbe-free bees had reduced expression of proteins which are key for olfaction. Interestingly, tryptophan metabolism was both up- and downregulated with the absence of gut microbes. There was an overall significant decrease in the levels of tryptophan and indole-3-acrylic acid as well as in the kynurenic acid/kynurenine ratio in microbe-free bees. Since there were alterations in tryptophan metabolism with the loss of the microbiota, the researchers looked at the genomes of  honeybee specific bacterial species to indentify potential tryptophan metabolizers. They identified that Lactobacillus apis express ArATs which suggests it can breakdown tryptophan. When microbe-free bees were recolonized with Lactobacillus there was in increase in indole derivatives and their memory was improved in the presence of tryptophan. Importantly, indole activation of the aryl hydrocarbon receptor (AhR) was shown to play a role in learning and memory behaviors. Taken together, these data demonstrates that the gut-brain axis plays a role in learning and memory via tryptophan metabolism.

Original Research: Zijing Zhang et al. (2022) Honeybee gut Lactobacillus modulates host learning and memory behaviors via regulating tryptophan metabolism. Nat Commun. DOI: 10.1038/s41467-022-29760-0