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in the gut-skin axis. The worm can be used to measure how probiotics improve gut health and provides the perfect bridge between animal models and cell models. As an invertebrate, C. elegans offers a sustainable option for testing products, consuming less energy, water, and resources than rodents. In addition, C. elegans is a more ethical model as it encounters no regulatory or ethical restrictions. C. elegans studies can significantly enrich and compliment data from other models and in vitro experiments.
Microscopic nematodes as a model for discovery C. elegans is a free-living nematode that feeds on bacteria in rotting vegetation. Through the extensive achievements of research groups across the world, C. elegans has become a powerful model system to study diverse aspects of biology such as programmed cell death, gene silencing, and neuronal function among others. C. elegans also became the first model
organism in which single gene mutations were found that slowed ageing, and thereby has become a powerful model for ageing studies. It has emerged to be extremely useful for nutraceutical discoveries. C. elegans is a great model for whole
organism physiology meaning interactions taking place between different organs or the gut-skin axis can be monitored. Researchers can look at movement, gut integrity, and metabolic health, as well as a cuticle formed from an epidermal layer that mirrors several functions of human skin. The integrity of the cuticle can be monitored as the worms age to see if probiotics have the desired beneficial effects. Due to the worm’s short yet well-defined
life cycle of three days and short lifespan of around three weeks, it is very well suited to study the biology of ageing and testing age- related skin problems. C. elegans is inexpensive to maintain, grows rapidly, and is genetically uniform, making it an excellent choice for large- scale experiments. In addition, large test populations can be
used, addressing the heterogeneous nature of ageing. Researchers can deliver ageing data within a couple of weeks versus several months. In vivo data with functional endpoints can be provided in just fourteen days to de-risk probiotic compound development and accelerate research. This approach helps the transition from in vitro studies to human studies, by testing probiotics earlier in a whole organism, without regulatory requirements.
Benefits of using C. elegans in probiotic research The worm’s translatability to humans, with up to 60-80% gene homology with cell types and organs found in humans, enables rational predictions of what could happen in humans treated with the same probiotic product. Importantly, C. elegans can be associated with a single strain of bacteria, making it straightforward to assess the effects of a single probiotic strain on development, movement, and ageing. Furthermore, genetic manipulation in
PERSONAL CARE November 2024 Worm picking
both C. elegans and the bacterial strain can provide valuable insights into the underlying mechanisms. Targeted mutations of genes in either the worm or the bacteria can be used to explore specific pathways potentially modulated by the probiotic. This approach can identify key genes and functions essential for the probiotic's efficacy. Once a specific probiotic strain's efficacy is
linked to the genes responsible for a particular function, researchers can leverage this knowledge to efficiently screen and identify other promising strains with similar genetic composition. This targeted screening strategy streamlines the identification of potentially efficacious probiotic candidates and can speed up research. C. elegans can serve as a powerful screening
tool for identifying novel probiotic strains with specific functionalities. The rapid life cycle and ease of manipulation in C. elegans enables researchers to efficiently evaluate large bacterial libraries for their potential health benefits. This approach can accelerate the discovery and development of new probiotic products addressing various skin-related health concerns. C. elegans opens new perspectives in
developing assays to investigate the cytotoxicity of new bioactive molecules or microbial pathogenicity and host defence mechanisms and gives new strategies to understand the mode of action (specific chemical, virulence factor). C. elegans allows a microorganism to be assessed in a whole animal with an integrated point of view, considering the gene expression using transcriptomic and proteomic approaches as well as metabolomics and physiology of the entire organism. While the bacterial communities that can colonise the C. elegans digestive tract contain a smaller number relative to humans, this feature enables the comprehensive study of simplified mock communities to understand the foundational mechanisms that govern host–microbe interactions. C. elegans offers a highly controlled and
reproducible experimental system. Its short life cycle, well-defined anatomy, and ease of cultivation allow for consistent results across replicate experiments. This is particularly advantageous in probiotic research, where complex interactions between the host and numerous microbial factors can occur. The standardized nature of the C. elegans model minimizes variables, facilitating robust and reliable data generation.
Using C. elegans in practice The short life cycle of C. elegans means that research can be done on ageing very quickly and by testing the bioactive ingredients of natural products, researchers can identify the effectiveness and mechanisms of action in products. The genetics of C. elegans combined with
the genetics in the probiotic strain can be used to understand which genes are important for positive effects on health. A study used C. elegans to identify the mechanism of a probiotic strain that suppresses age-dependent neurodegeneration. The data generated suggests that disrupted lipid metabolism contributes to neurodegeneration and that dietary intervention with Lacticaseibacillus rhamnosus HA-114 restores lipid homeostasis and energy balance through mitochondrial β-oxidation.9 Another study investigated probiotic
interventions affecting stress and longevity involving the potential therapeutic value of Lactococcus lactis and Leuconostoc mesenteroides isolated from organic basil using a C. elegans model.10
The results emphasised
the potential probiotic applicability of these biomarkers for predicting early health responses. To develop a model to understand skin
ageing, a recent study developed two methods to assess C. elegans’ cuticle, which forms the barrier between the animal and its environment, and is formed from a layer of epidermal cells. It found that with age the cuticle stiffens and that collagen mutations alter the integrity of the cuticle by significantly changing its elasticity.11 Using this approach, probiotics that slow ageing can be assessed for their ability to maintain integrity of the C. elegans equivalent of skin.
Conclusion As ageing becomes an ever-increasing problem around the world, age-related health issues are on the rise. There is growing evidence that there is an important relationship between the gut microbiome and skin health, with gut microbiome dysregulation a common symptom in many skin-related diseases. This has led to the nutraceutical industry
developing treatments for age-related skin problems through the use of probiotics. To test those probiotics, there is a need for a more ethical and sustainable whole-body organism that can speed up time to result and help researchers fully understand the mode of action of bacterial strains. C. elegans emerges as a powerful tool not
only for probiotic development, but also for the creation of ingredients in pharmaceuticals and nutraceuticals. The tiny nematode worm has
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