Host-microbe interactions regulate mitochondrial function and lipid metabolism in Caenorhabditis elegans

Alterations in microbiome composition are strongly linked with metabolic dysfunction and obesity. Recent research has demonstrated that the well-characterised model organism Caenorhabditis elegans selectively associates with distinct microorganisms from its natural environment, forming a rich and diverse microbiome. As a result, C. elegans has emerged as a cost-effective, simple and experimentally tractable model for host-microbiome interactions.

This work leveraged this system to investigate the physiological impact of the natural C. elegans microbiome, modelled with a representative 11-member experimental microbiome, focusing on metabolic processes, mitochondrial functions and motility. This community selectively colonised the host intestine and supported development, but slightly reduced lifespan, fecundity and body size. The experimental microbiome preserved age-related motility rates without affecting muscular structure or neuromuscular transmission. Instead, this phenotype was associated with mitochondrial network fragmentation and the preservation of age-related ATP levels in the body wall muscles. Respirometric analysis using a set of novel, low-cost respirometric protocols showed that the experimental microbiome also elevated mitochondrial respiration. These mitochondrial phenotypes were accompanied by reduced fatty acid biosynthetic activity, higher lipid catabolic activity, alterations in the age-dependent expression of the mitochondrial β oxidation gene acdh-1, and drastically reduced neutral lipid storage. Motility analyses suggested that a subset of these metabolic changes were involved in the preservation of age-related motility rates, specifically via the mitoUPR regulator ATFS-1, the mitochondrial fission regulator DRP-1, and the mitochondrial β oxidation enzyme ACDH-1.

This work illustrates a complex relationship between the natural C. elegans microbiome and host metabolism, inducing mitochondrial fragmentation without functional impairment and maintaining age-related motility through specific mitochondrial processes. We propose that these changes may enhance mitochondrial β-oxidation, improving muscular bioenergetics

and thus preserving age-related motility rates.