Pathogenic puzzle: NanoSIMS imaging unlocks bees’ ability to synthesize nutrients for microbes

17 Jan 2024 --- A team of Switzerland-based researchers demonstrated that honey bees synthesize nutrients for their native gut microbes. Experimentation to prove their hypothesis was complex — conducted using one of a handful of Nanoscale Secondary Ion Mass Spectrometry (NanoSIMS) instruments in Europe — but the mechanisms under analysis could play a role in reducing bees’ vulnerability to climate change, pesticides or new pathogens.

Bees are essential foot soldiers of the food system because they pollinate crops. Research about their well-being is critical to understanding how ecosystems function and mitigating the threat of food insecurity.

“We have uncovered a tight metabolic link between bees and their microbes. Bees metabolize sugars in their diet and convert them into organic acids that are exported into the gut, where the native microbiota uses them for energy,” Dr. Andrew Quinn, research scientist in the department of fundamental microbiology at the University of Lausanne and co-lead author of the study, tells Nutrition Insight. “This metabolic linkage between the host and its microbes may explain why bees have such a distinct, specific and stable microbiome.”

The research team specializes in measuring metabolite flux in complex environments at nanometer-scale resolution. They devised an experiment in which microbiota-free bees received a special diet of glucose where the natural 12C atoms of carbon in the glucose were replaced with the naturally rare 13C labeled isotopes. The bees were then colonized with a specific gut bacterium called Snodgrassella alvi (S. alvi). 

Toiling studiously for a 2D snapshot
The fixed guts were first examined using electron microscopy, followed by a NanoSIMS assessment. As a result, the scientists constructed a two-dimensional “image” of the 13C atoms in the bee’s gut, which showed that the S. alvi cells were significantly enriched at that temperature. The snapshot also reflected the 13C enrichment of the acids.

“Bees have co-evolved with their specialized gut microbes for 80–100 million years. Researchers have already found that these native microbes are critical for bee health. They protect against pathogens, help break down nutrients in the diet and produce beneficial neuroactive compounds that aid the bees’ cognitive function,” Quinn outlines. 

The image successfully captured how the bee synthesizes food for its intestinal bacteria. Bees are helping scientists understand how a host provides nutrients to bacteria to help them colonize the gut. Many other gut microorganisms could also feed on host-derived compounds. The study’s findings can help explain why bees have such a specialized and conserved gut microbiota. 

“We know that a healthy microbiota is important for health, and we also know that stresses like newly emerging pathogens and pesticides have been linked to dysbiosis in the bee gut. A lot of attention has focused on how bees change their foraging habits, but no one has closely looked at how these stresses could alter the bee’s metabolism and how that, in turn, impacts the gut microbiota,” Quinn explains.NanoSIMS technology was used to capture the nutrient sharing process between the bee and its gut bacterium S.alvi (Credit: EPFL/Alain Herzog). 

The bee’s metabolism could be crucial in reevaluating the impact of pesticides on bees, as many exert subtly detrimental effects that damage bee colonies over the long term or make them just a bit more susceptible to pathogens that can destroy the colony. Their vulnerability could result from disrupting the intricate metabolic synergy between the bee and its gut microbiota. 

Nutrient sharing
The study, published in Nature Microbiology, began by looking for evidence that the bacteria share nutrients when bees receive nothing more than sugar water. This was based on the behavior of bees who love to gorge on nutrient-rich pollen and honey but can also survive for long periods on sugar water. 

Next, they looked at the effect on the bacteria when the diet was altered. Intestinal bacteria consume dietary nutrients and waste products from other microorganisms. The researchers discovered that S.alvi still colonized the bee’s gut when only sugar was consumed and no other bacteria were present, even though it cannot metabolize sugar to grow.

By measuring metabolites, they discovered that the bee synthesizes multiple acids such as citric acid, malic acid and 3-hydroxy-3-methylglutaric acid, which are exported into the gut and were less abundant when S. alvi was present. 

The findings led them to speculate that the bee directly enables S. alvi to colonize its gut by giving it access to the necessary nutrients. Bacteria have adapted to all terrestrial environments — some have evolved to survive in the gut of animals, where they provide energy by breaking down indigestible food.

In addition, these bacteria train and regulate the immune system, protect against the invasion of pathogenic bacteria and synthesize neuroactive molecules that regulate the behavior and cognition of the host. 

“We don’t yet know whether or how changes in diet alter the secretion of metabolites from the host into the gut. However, recent publications in other animal models have shown that gut microbes, both commensal species and pathogens, can significantly benefit from host-derived compounds,” explains Quinn.The research findings provide a foundation for future research into bee metabolism. 

“These congruent findings across divergent host species suggest that the phenomenon is widespread and needs to be studied in more detail when considering metabolic exchange and dependencies between humans and their gut microbiota.”  

Meanwhile, US-based researchers successfully treated honey bees with a novel immune system booster for deadly viruses causing losses of critical pollinators on a global level. In addition, omega 3-rich ahiflower oil demonstrated promising immune-boosting properties to reverse the damage caused to the mitochondria of honey bees from exposure to neonicotinoid pesticides, according to ongoing research conducted at the Université de Moncton in Canada.

Comparing bee and human gut behavior
While bees are best known for their honey, they provide an ideal experimental model for gut microbiota research. These creatures have acquired a “remarkably” simple and stable microbiota with around twenty bacterial species. 

Researchers in the department of fundamental microbiology at the University of Lausanne have raised bees without gut bacteria and then fed them specific bacterial species that will colonize the gut. Professor Philipp Engel plans to take the research a step further by analyzing the western honey bee (Apis mellifera), which has a relatively simple system to study compared to humans and their gut microbiota. 

“Honey bees receive the lion’s share of attention because we are so familiar with them, and because of their economic value. However, concern for bee health should be focused on wild bee species suffering far more than managed honey bees,” says Quinn. 

“Our research is relevant here, too, because the bacterial genus Snodgrassella that we have studied is also found in many species of honey bees, stingless bees and bumblebees. We found that species of Snodgrassella native to bumblebees also feed on host-derived compounds when transplanted into the gut of honey bees, but further research is needed to confirm these findings in other bee species,” he concludes. 

By Inga de Jong