C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1

Publikation: Bidrag til bog/antologi/rapport/konference proceedingKonferenceabstrakt i proceedingForskning

Resumé

Introduction
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.
Method
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.

Results
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.

Discussion
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.
OriginalsprogEngelsk
TitelC. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1
Publikationsdatojun. 2018
StatusUdgivet - jun. 2018
BegivenhedInternational Scientific Conference on Probiotics, Prebiotics, Gut Microbiota and Health 2018 - Budapest, Ungarn
Varighed: 18 jun. 201821 jun. 2018

Konference

KonferenceInternational Scientific Conference on Probiotics, Prebiotics, Gut Microbiota and Health 2018
LandUngarn
ByBudapest
Periode18/06/201821/06/2018

Fingerprint

Caenorhabditis elegans
Probiotics
p38 Mitogen-Activated Protein Kinases
Methicillin-Resistant Staphylococcus aureus
Enterotoxigenic Escherichia coli
Bacteria
Lactobacillus
Immune System
Health
Clustered Regularly Interspaced Short Palindromic Repeats
Genome
Microbiota
Dietary Supplements
Nervous System
Intestines
Immunity
Mental Health
Hypersensitivity
Obesity
Diet

Citer dette

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title = "C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1",
abstract = "IntroductionA 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. MethodTo 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. Results 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. DiscussionInterestingly, 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.",
author = "Hesselager, {Marianne Overgaard} and Harders, {Rikke Hindsgaul} and M{\o}ller, {Katrine Vogt} and M{\o}rch, {Maria Grymer Metz} and Anders Olsen",
year = "2018",
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language = "English",
booktitle = "C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1",

}

Hesselager, MO, Harders, RH, Møller, KV, Mørch, MGM & Olsen, A 2018, C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1. i C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1. International Scientific Conference on Probiotics, Prebiotics, Gut Microbiota and Health 2018, Budapest, Ungarn, 18/06/2018.

C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1. / Hesselager, Marianne Overgaard; Harders, Rikke Hindsgaul; Møller, Katrine Vogt; Mørch, Maria Grymer Metz; Olsen, Anders.

C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1. 2018.

Publikation: Bidrag til bog/antologi/rapport/konference proceedingKonferenceabstrakt i proceedingForskning

TY - ABST

T1 - C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1

AU - Hesselager, Marianne Overgaard

AU - Harders, Rikke Hindsgaul

AU - Møller, Katrine Vogt

AU - Mørch, Maria Grymer Metz

AU - Olsen, Anders

PY - 2018/6

Y1 - 2018/6

N2 - IntroductionA 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. MethodTo 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. Results 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. DiscussionInterestingly, 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.

AB - IntroductionA 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. MethodTo 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. Results 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. DiscussionInterestingly, 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.

M3 - Conference abstract in proceeding

BT - C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1

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Hesselager MO, Harders RH, Møller KV, Mørch MGM, Olsen A. C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1. I C. elegans reveals probiotic secrets: L. brevis increases lifespan via the p38 MAP kinase PMK-1. 2018