Examining effects of native microbiota on host ageing in Caenorhabditis elegans

The gut microbiome modulates many aspects of host physiology, including the ageing process. There is a pressing need for suitable, tractable models with which to investigate how host-microbe interactions affect host ageing. Studies performed in the nematode Caenorhabditis elegans have made significant contributions to biological research but have largely been performed outside the context of the nematode's native microbiota. A growing body of evidence has demonstrated that wild C. elegans harbour a rich and diverse community of commensal microorganisms. Here, we leverage the combined model system of C. elegans and ecologically relevant symbionts to identify the pathways underlying microbiome effects on age-related phenotypes in the host. In this study, eleven ecologically relevant bacterial species were selected to model the native C. elegans microbiome. This microbial assembly, referred to as the Experimental Microbiome, was found to survive in the nematode intestine and support normal development. Colonisation with native microbiota members suppressed age-associated locomotor decline - an effect that does not involve modifications to muscle structure or function but requires the engagement of various signalling pathways in the host. The genetic components of innate immunity, iron processing, and mitochondrial homeostasis are all required for Experimental Microbiome-mediated preservation of motor function. Indeed, cultivation on the Experimental Microbiome alters mitochondrial network dynamics and occludes normal patterns of mitochondrial ageing. The Experimental Microbiome was also found to suppress age-associated proteotoxicity in a transgenic C. elegans strain expressing human amyloid beta, with protection provided by live bacteria as well as cell-free extracellular material. Altogether, this work highlights the microbiome's capacity to influence host ageing by engaging host signalling pathways and illustrates the potential of targeting host-microbe interactions to extend healthspan.