Breaking down the microbiology world one bite at a time
Honeybee’s learning and memory rely on gut bacteria
Bacteria can be good or bad, but contrary to popular beliefs, most are good. Some of these good bacteria are actually a major component of our and other species bodies. Gut microbiomes, in almost every species, have evolved to have essential roles in species survival. Cows, for example, have special symbiont bacteria that allow them to digest and retrieve nutrients from foods that are otherwise indigestible by mammals, such as grass (cellulose). It is also widely established now that a healthy gut microbiome is crucial for good health and plays major roles in modulating metabolism and immune functions in mammals and other species.
Recently, studies are also demonstrating a functional connection between the neurological functions and mammalian microbiomes. One example of this phenomenon is demonstrated by the gut microbiome’s role in tryptophan metabolism producing serotonin, a molecule responsible for controlling our mood and sleep in the brain. In this case, loss of the healthy gut microbiome could lower serotonin levels and consequently lead to poor mood and sleep over time.
This brain-gut connection prompted Zheng et al. (2022) to wonder if this gut microbiome- brain connection extends to the host’s social behaviors and cognition as well. To investigate this exciting question, they used honeybees as a model organism as these have a small, specialized gut microbiome (easy to manipulate) and form highly social and interactive communities. Honeybee’s gut microbiome is already known to play defined roles in immune homeostasis, metabolism and pathogen resistance. Their gut microbiome is also involved in communication between bees and kin recognition.
Zheng et al. exposed honeybees to antibiotic treatments and returned them to the hives to observe changes in their behavior/ health compared to untreated bees (Figure 1). They found that antibiotic exposure, which disturbed gut microbiome, made the bees less fertile and they produced less offspring. Interestingly, they also seemed to suffer from malnutrition. This then raised the question of why the bees were malnutritioned and if it had something to do with their neurological functions, particularly relating to their memory and olfactory learning.
They therefore chose to explore these traits further as they are important for many of their social behaviors, such as labor division, kin recognition, and mating. As hypothesized, bees with disrupted gut microbiomes performed worse compared to bees with healthy microbiomes in a olfactory learning task where they had to associate a particular odor with a sugar reward (Figure 2). And none of the bees with disrupted microbiomes could remember odor-reward association in a later memory task. This depicts how the gut microbiome affected the bees’ learning and memory abilities.
They further explored this qualitative in-field observation by using quantitative genetic approaches to determine changes at a genetic level. They found the bees with healthy gut microbiomes had distinct brain gene expression profiles from the bees with disturbed microbiomes. In particular, disturbed gut microbiomes downregulated the expression of many genes important for honeybee learning and memory.
Next, they wanted to determine the mechanism of how these gut microbes influence memory, so they performed a metabolic analysis to compare the differences between the antibiotic-treated and untreated bees. The different gut microbes altered the tryptophan metabolism, an essential amino acid for proper growth & development.
In particular, there are two tryptophan breakdown pathways as seen in figure 3, one mediated by gut microbe enzymes (ArAT enzyme, conserved in some gut microbe species) which produces indole derivatives (known to be important for maintaining intestinal health) and another mediated by host enzymes which produces Kyn (associated with neurodegenerative diseases). Overall, their study shows that healthy gut microbes expressing ArAT enzyme, which in the case of honeybees was Lactobacillus apis, promote tryptophan breakdown through the indole pathway and limit the Kyn pathway which produces harmful metabolites for neurological function.
Now that they knew that the tryptophan metabolism was modulated by Lactobacillus apis, they wanted to know how this led to behavioral changes between the two groups of bees. They observed that the indole derivatives produced were ligands of an intestinal transcription factor, AhR; that is the two fit together like a jigsaw puzzle and result in the activation of other important functions, like memory and learning (Figure 3). They confirmed this by treating a group of healthy gut microbiome bees with an AhR-antagonist (a molecule which would inhibit AhR activation and function) and observed worsened performance at the olfactory learning and memory task (Figure 2).
These results are quite fascinating as they reveal an additional critical role the gut microbiome and individual bacteria can play in the host. While this study demonstrated the role of gut bacteria in regulating memory and learning in bees, it potentially could also have some parallels in mammals. For instance, we also have gut microbes regulating tryptophan metabolism, which could potentially have important roles in our neurological functions. Next, it would be quite interesting to explore the role of the mammalian gut microbiome in learning and memory.
Featured image: By Ivar Leidus – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=50535031