Probiotic Lactobacillus spp. improves Drosophila memory by increasing lactate dehydrogenase levels in the brain mushroom body neurons

ABSTRACT

Probiotics are live microorganisms that offer potential benefits to their hosts and can occasionally influence behavioral responses. However, the detailed mechanisms by which probiotics affect the behavior of their hosts and the underlying biogenic effects remain unclear. Lactic acid bacteria, specifically Lactobacillus spp. are known probiotics. Drosophila melanogaster, commonly known as the fruit fly, is a well-established model organism for investigating the interaction between the host and gut microbiota in translational research. Herein, we showed that 5-day administration of Lactobacillus acidophilus (termed GMNL-185) or Lacticaseibacillus rhamnosus (termed GMNL-680) enhances olfactory-associative memory in Drosophila. Moreover, a combined diet of GMNL-185 and GMNL-680 demonstrated synergistic effects on memory functions. Live brain imaging revealed a significant increase in calcium responses to the training odor in the mushroom body β and γ lobes of flies that underwent mixed feeding with GMNL-185 and GMNL-680. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and whole-mount brain immunohistochemistry revealed significant upregulation of lactate dehydrogenase (LDH) expression in the fly brain following the mixed feeding. Notably, the genetic knockdown of Ldh in neurons, specifically in mushroom body, ameliorated the beneficial effects of mixed feeding with GMNL-185 and GMNL-680 on memory improvement. Altogether, our results demonstrate that supplementation with L. acidophilus and L. rhamnosus enhances memory functions in flies by increasing brain LDH levels.

KEYWORDS:

• Probiotics
• Lactobacillus
• Brain
• Olfactory memory
• Lactate dehydrogenase
• Drosophila melanogaster

Acknowledgments

We are grateful to the Bloomington Drosophila Research Center and Flycore (Taiwan) for providing fly stocks. We thank Yi-Hua Li for the help with the initial behavioral screening. We would also like to thank the members of Prof. Chia-Lin Wu’s laboratory for helping with manuscript preparation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

Conceptualization, S-MH, W-HT, C-HL, and C-LW; Methodology, S-MH, W-HT, C-HL, M-HC, W-PL, H-YW, P-YB, T-W, and C-LW; Validation, S-MH, M-HC, W-PL, H-YW, and P-YB; Investigation, S-MH, M-HC, W-PL, H-YW, and P-YB; Resources, W-HT and C-LW; Data curation, S-MH, M-HC, W-PL, H-YW, and P-YB; Original draft preparation, S-MH and C-LW; Review and editing, S-MH, W-HT, C-HL, and C-LW. Supervision, C-LW; Funding acquisition, C-LW. All authors have read and agreed to the published version of the manuscript.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Material. The datasets generated for this study can be found in the https://reurl.cc/G4ANrG

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2316533

Additional information

Funding

This work was funded by the grant from Ministry of Science and Technology, Taiwan (112-2311-B-182-002-MY3), grants from Chang Gung memorial hospital (CMRPD1M0301-3, CMRPD1M0761-3, and BMRPC75), grant from Science Park, Ministry of Science and Technology (109CB01), and Research Center for Emerging Viral Infections from the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Taiwan Ministry of Education.