Luna Segarra Alonzo¹, Cecilia Fadhel¹, Angelie Nuñez Colón¹, Imilce A. Rodríguez-Fernandez¹

¹College of Natural Sciences, Department of Biology, University of Puerto Rico, Rio Piedras

Introduction: The gut microbiota is composed of microorganisms, including intestinal bacteria, which play a fundamental role in the health and well-being of the host. Recent findings have uncovered that the gut microbiota can influence the functions of distant organs, such as the brain, through what is known as the Gut Microbiota-Brain axis. Among the bacteria that reside in the gut, there are those with anti-inflammatory and antioxidant properties that can benefit the overall health of the host. These bacteria are categorized as ‘good bacteria’ or probiotics and are defined by the World Health Organization as “live microorganisms which when administered in adequate amounts confer a health benefit on the host”. However, we still lack information on how these probiotics provide these benefits and their influence on the gut-brain axis. It has been shown in flies and mice that L. plantarum can activate the conserved transcription factor known as Nrf2 (in mammals) / CncC (in flies) in the gut and liver, respectively. This Nrf2/CncC activation by L. plantarum provided cytoprotection to the animals by activating the antioxidant response.

Objectives: This project investigates the potential brain-specific activation of the conserved transcription factor Nrf2/CncC by the probiotic bacteria Lactiplantibacillus plantarum (L. plantarum).

Methods: To achieve our goal, we are using the fruit fly Drosophila melanogaster as a model system, specifically transgenic larvae carrying an Nrf2/CncC genetic reporter. Our approach involves several key steps: (I) Culturing L. Plantarum from a glycerol stock and cultivating them in MRS Broth, (II) Collecting transgenic larvae during the 2-3rd instar stage and exposing them to L. Plantarum for 24 hours, (III) Dissecting and preserving the gut, brain, and fat body tissues in 4% formaldehyde overnight, and (IV) Performing immunohistochemistry and analyzing the tissues using fluorescence microscopy.

Results: Our preliminary data shows that larvae fed L. plantarum as a probiotic for 24 hours is sufficient to activate Nrf2/CncC in the brain optic lobe. Future functional genomics experiments will be done to understand the physiological consequences of L. plantarum-mediated Nrf2/CncC activation in the brain and whether this has a role in brain development.

Conclusions: Data coming from this project will provide additional evidence on how the gut microbiome can influence the brain and provide a benefit to the animal.

Acknowledgements: LS thanks UPRRP Honors Program, Dr. Esther Peterson lab (UPRRP) and the NIEF confocal facilities (UPR Molecular Science Building). IARF funding provided by NIH-NIGMS COBRE (5P20GM103642-10) and the Catalyzer Research Grant (#2023-00056) Puerto Rico Science, Technology & Research Trust (PRST). Thanks to W. Ludington from Carnegie Science for providing LpWF strain.