Similar to humans, honey bees possess a core gut microbiota that helps mitigate dietary toxins, fight pathogens, and provides a wide range of other health benefitis¹. In our recently published article in Communications Biology² we asked the question, could routine antibiotic treatment with oxytetracycline (used to prevent deadly bacterial infections, namely by Paenibacillus larvae) represent an underappreciated stressor of honey bees through damaging their health-promoting gut microbiota?

Investigating this, we sampled honey bee hives before, during, and after oxytetracycline exposure during a two-week treatment regimen. The findings demonstrated that oxytetracycline depletes several key symbionts known to regulate immune function and nutrient metabolism, such as Frischella perrera and Lactobacillus Firm-5 strains. Exposure to the drug also enriched for an antibiotic resistance efflux pump gene (tetB) in the gut microbiota of adult bees.

These findings are important as they suggest that apicultural antibiotic usage may be harming the long-term health trajectory of honey bees as well as contributing to the environmental dissemination of antimicrobial resistance elements. Corroborating previous work, functional hive markers pertaining to nutritional status, productivity, and immune status were also decreased by oxytetracycline.

As researchers interested in using beneficial microbes to counter disease, we postulated that a set of three immunostimulatory Lactobacillus strains (LX3) already shown to reduce P. larvae infectivity³ (previously shared in a post on this forum last year) could be used to mitigate some of the negative side effects of oxytetracycline. Following cessation of antibiotic treatment, a BioPatty containing LX3 plus essential nutrients was placed inside the hive once a week for four weeks.

Making the BioPatty in lab (left two photos) and top side brood chamber photos from before and after consumption by honey bees (right two photos, respectively).

In addition to significantly improving immune function, LX3 also partially mitigated antibiotic-induced microbiota dysbiosis, restored hive productivity deficits, and reduced pathogen load of P. larvae beyond that of antibiotics alone relative to the vehicle treatment group. These findings fit nicely with our previous work^3–6 suggesting the primary mechanism governing a favourable response to LX3 is through activation of host Imd pathway signalling leading to downstream production of antimicrobial peptides with microbiota-shaping properties (i.e. selective toxicity towards environmental opportunists and pathogens, but not core symbionts).

Some critics have raised concerns that we are altering the microbiota of honey bees by inserting ‘foreign’ lactobacilli strains. This would be a legitimate issue if the non-native lactobacilli in LX3 colonized the host long-term. But this is not the case and, in general, colonization is not a prerequisite for benefits to be observed from probiotic supplementation^7,8.

Honey bees support approximately 1/3^rd of the global food supply, but they are threatened by habitat loss, pesticides exposure, and infectious diseases. We can’t counter all of these issues, but ultimately, our findings could address the latter two problems. In this instance, certain probiotic lactobacilli used in conjunction with standard antibiotic therapy may help maintain healthy honey bee populations.

If implemented, this novel combination strategy could significantly reduce environmental dissemination of antibiotic resistance as well through minimizing the frequency at which antibiotics are necessitated to prevent honey bee disease outbreaks from occurring, such as American and European foulbrood diseases shown below.

Simplified schematic showing how combination therapy may reduce the frequency at which antibiotics are needed to control common but deadly honey bee pathogens.

One day, we might even be able to drop antibiotic supplementation altogether and allow the probiotic strains and natural antimicrobial activity within the bees counteract P. larvae and potentially other pathogens. However, for this to be effective, the same rigorous testing that is done in human clinical trials needs to be applied. Unfortunately, some companies might consider simply isolating a honey bee-specific Lactobacillus strain and then calling it a probiotic (without any prior evidence). Though, this is unacceptable in practice and not proof of probiotic effects. Let patience and thorough science be the markers of success before commercialization. On that front, we note that all our research on this topic is disclosed to the public and not driven by commercial interest.

Long may our fuzzy pollinator friends fly.

References

1. Kwong, W. K. & Moran, N. A. Gut microbial communities of social bees. Nat. Rev. Microbiol. 14, 374–384 (2016). doi: 10.1038/nrmicro.2016.43
2. Daisley, B. A. et al. Lactobacillus spp. attenuate antibiotic-induced immune and microbiota dysregulation in honey bees. Commun. Biol. 3, 534 (2020). doi: 10.1038/s42003-020-01259-8
3. Daisley, B. A. et al. Novel probiotic approach to counter Paenibacillus larvae infection in honey bees. ISME J. 14, 476–491 (2019). doi: 10.1038/s41396-019-0541-6
4. Daisley, B. A. et al. Neonicotinoid-induced pathogen susceptibility is mitigated by Lactobacillus plantarum immune stimulation in a Drosophila melanogaster model. Sci. Rep. 7, 2703 (2017). doi: 10.1038/s41598-017-02806-w
5. Chmiel, J. A., Daisley, B. A., Burton, J. P. & Reid, G. Deleterious effects of neonicotinoid pesticides on Drosophila melanogaster immune pathways. mBio 10, e01395-19 (2019). doi: 10.1128/mBio.01395-19
6. Daisley, B. A., Chmiel, J. A., Pitek, A. P., Thompson, G. J. & Reid, G. Missing microbes in bees: how systematic depletion of key symbionts erodes immunity. Trends Microbiol. (2020) doi: 10.1016/j.tim.2020.06.006.
7. Hill, C. et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 11, 506–514 (2014). doi: 10.1038/nrgastro.2017.75
8. Sanders, M. E., Merenstein, D. J., Reid, G., Gibson, G. R. & Rastall, R. A. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat. Rev. Gastroenterol. Hepatol. 16, 605–616 (2019). doi: 10.1038/s41575-019-0173-3

Photographs by Andrew Pitek.