EXOPOLYSACCHARIDE-PRODUCING GUT BACTERIA MODULATE HOST AGEING

Abstract

Introduction: New theories of ageing recognized gut microbiota as one of twelve hallmarks of ageing (1). Recent data conducted on Caenorhabditis elegans imply a potential role of Lactobacillus species and other commensal bacteria in regulation of ageing highlighting TFEB/HLH-30-dependent autophagy, p38 MAPK/PMK-1 signalling and mitochondrial function as activated longevity-associated mechanisms (2,3). Here, we explore the potential of bacterial polysaccharides loosely attached to bacterial cell wall (exopolysaccharides), considering it is still unknown which bacterial molecules could activate longevity signalling pathways. Materials & Methods: Caenorhabditis elegans was used as ageing model. Evaluation of worm’s lifespan and locomotion rate were performed by feeding worms with six exopolysaccharide-producing lactobacilli. Worms fed with two selected strains were subjected to RNAseq analysis. Identified upregulated genes were confirmed by qPCR and expression of their mammalian orthologs checked in human HepG2 cell. Results: Two strains of lactobacilli showed the most pronounced effect on worms’ lifespan. RNAseq analysis identified core gene signature associate with exopolysaccharide-induced longevity. The expression of identified fmo-2, gsto-1, nlp-29, and clec-47 genes were confirmed by qPCR, while upregulation of FMO-5 was confirmed in HepG2 cells. Conclusion: Overall, our results imply that bacteria-derived exopolysaccharides could stimulate longevity- promoting flavin-containing monooxygenase 2 to regulate lifespan in Caenorhabditis elegans