Honeybees fed D-galactose exhibit aging signs with changes in gut microbiota and metabolism

ABSTRACT Honeybees ( Apis mellifera ), as social insects, exhibit complex social behaviors and cognitive functions. The short lifespan and stable gut microorganisms of honeybees provide certain availability as a rapid and high-flux animal model for aging research. This study explored the effect of D-galactose, a common aging inducer, on honeybees and investigated the associated effects and mechanisms, with particular focus on the potential protective role of sodium butyrate. Experimental cohorts were established as follows: conventional (CV) group, D-galactose-treated (DG) group, and sodium butyrate-treated (SB) group. The CV group was fed sucrose solution; the DG group was fed D-galactose solution; and the SB group was fed D-galactose and sodium butyrate solution. A comprehensive assessment was conducted on day 15 post-treatment, including survival analysis, starvation test, motor, learning and memory ability tests, malondialdehyde test, and Smurf test. Potential mechanisms through the microbiome and metabolome were investigated. Compared to the honeybees from the CV group, those in the DG group showed a shortened lifespan, a weaker energy storage ability, impaired motor, learning, and memory abilities, reduced weight, increased oxidation, and a disrupted gut barrier. These phenotypic changes were associated with microbial dysbiosis characterized by Lactobacillus enrichment and diminished butyrate levels. Notably, sodium butyrate supplementation extended the honeybees’ lifespan and improved their learning and memory abilities damaged by D-galactose. Our findings establish honeybees as a valuable model system for aging research and highlight the crucial role of butyrate metabolism in senescence regulation. IMPORTANCE This study presents a novel approach to investigating aging processes by establishing a D-galactose-induced aging model in honeybees. Our findings demonstrate that butyrate supplementation effectively attenuates D-galactose-induced senescence phenotypes, suggesting its potential as a therapeutic intervention for age-related decline. This research provides a unique model system for aging studies and highlights the significant role of butyrate in modulating senescence progression. The results contribute to our understanding of the molecular mechanisms underlying aging and offer new insights into potential anti-aging strategies.