A wealth of links between the gut microbiota and health is currently being discovered (i.e. obesity, diabetes, allergy, cancer, immunity, mental health and even aging) in humans, animals and plants. In order to modulate the microbiota composition and thereby influence host health, probiotics have been widely studied. Many positive effects of probiotics have been reported. However, we need to dig deeper into the host response to further our understanding of probiotics and their beneficial potential. Deciphering probiotic mechanisms of action would help unlock their potential as food and feed supplementation.
To discover new probiotic bacteria and gain further insight into their molecular mechanisms, we use Caenorhabditis elegans as model organism. C. elegans is a transparent, short-lived, self-fertilizing hermaphroditic nematode with a fully sequenced genome. It contains many of the same basic anatomical features as higher organisms, among others a nervous system, an intestinal tract and an immune system. Many human gene homologues have been identified in the C. elegans genome, allowing the study of conserved pathways, and many mutants are available or can be created easily using CRISPR. Additionally, C. elegans is particularly well suited for host-bacterial studies as their natural diet consists of bacteria.
This project is a collaboration with DuPont Nutrition Biosciences Aps, who provided 125 Lactobacillus (LAB) strains. We tested their health promoting effects in C. elegans by focusing on three different probiotic effects: 1) lifespan extension, 2) reduction of intestinal colonization of pathogenic bacteria, and 3) protection against killing by pathogens.
We established a C. elegans lifespan screening protocol and identified 15 LAB strains with life-extending effects. Via epistasis analysis, we found that an L. brevis strain increased longevity dependent on the P38 MAPK PMK-1, which is part of the innate immune system. Using a reporter strain expressing GFP-tagged PMK-1 we found that PMK-1 levels are increased following feeding with this L. brevis.
Many different pathogenic bacteria can colonize the intestine of C. elegans and eventually kill the animals. We examined two different pathogens: Methicillin-resistant Staphylococcus aureus (MRSA) and a mammalian F18 fimbriated Enterotoxigenic Escherichia coli (F18 ETEC) strain, which to our knowledge has not before been used in C. elegans pathogen assays. We found that both the MRSA and F18 ETEC bacteria were pathogenic to C. elegans and dramatically shortened their lifespan. By pre-treating worms with L. brevis before pathogen encounter, we obtained full protection against intestinal colonization by F18 ETEC. L. brevis pre-treated worms were protected against MRSA-induced killing.
Interestingly, not all LAB strains, in fact not all L. brevis strains increased lifespan and conferred protection against MRSA. Hence, the mechanisms by which L. brevis exerts probiotic effects are highly strain specific and more studies are needed to further understand their mechanism of action.
|Publication date||Jun 2018|
|Publication status||Published - Jun 2018|
|Event||International Scientific Conference on Probiotics, Prebiotics, Gut Microbiota and Health 2018 - Budapest, Hungary|
Duration: 18 Jun 2018 → 21 Jun 2018
|Conference||International Scientific Conference on Probiotics, Prebiotics, Gut Microbiota and Health 2018|
|Period||18/06/2018 → 21/06/2018|