Deciphering How Natural Host-Microbe Interactions Affect Age-Related Health in C. elegans

There is a considerable gap between human life expectancy and healthy life expectancy across the globe with a vast amount of time spent in ill health during advanced age. With a wealth of evidence that ageing and age-related diseases are associated with dysbiosis of the gut microbiota, the key to promoting lifelong health may lie in our guts. However, precise mechanisms in which the host and microbiota interact are yet to be deciphered. With mechanistic studies being ethically and technically challenging in humans, this project has utilised the nematode worm Caenorhabditis elegans due to its short lifespan, bacterivorous nature and an expanse of genetic tools available. To understand how host-microbe interactions influence age-associated stresses, the nematodes were cultured on a simplified community of 11 bacterial species, the experimental microbiome, representing those that colonise the gut of C. elegans isolated from their natural habitat.

Colonisation of the C. elegans gut microbiota by the experimental microbiome allows them to develop at the same rate as on their standard E. coli OP50 diet, although it negatively impacts lifespan and fecundity. The experimental microbiome protects C. elegans against infection by the pathogen S. aureus and this was mediated by interactions between live bacteria and the PMK-1 / p38 MAP kinase pathway and the HLH-30 / TFEB transcription factor. Furthermore, C. elegans cultured on the experimental microbiome have reduced amyloid-β toxicity and amyloid plaque formation in an Alzheimer's disease pathology model and a reduction in amyloid-β toxicity is also observed when the experimental microbiota bacteria are heat- and UV-killed.