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Predicting in vivo therapeutic efficacy of probiotics in a mouse model of Multiple Sclerosis, based on a novel in vitro Peyer’s Patch cell culture system

Gullberg, Martina (2015) MOBT01 20142
Degree Projects in Molecular Biology
Abstract
There is a great interest in trying to pin-point strain specific effects of probiotics on the immune system. The present study compared desirable immunomodulatory properties of newly isolated, novel probiotic strains of different species in a mouse Peyer’s Patch (PP) cell model in vitro, mainly focusing on their ability to affect the population of CD4+FoxP3+ regulatory T cells (Treg), and in increasing IL-10 expression. Mouse PP cells were stimulated with live probiotic lactobacilli and the immunological profile was investigated by flow cytometry. We found that only certain probiotic strains had the potential to induce Treg activation and IL-10 expression. In addition, we could also show that carefully selected combinations of strains were... (More)
There is a great interest in trying to pin-point strain specific effects of probiotics on the immune system. The present study compared desirable immunomodulatory properties of newly isolated, novel probiotic strains of different species in a mouse Peyer’s Patch (PP) cell model in vitro, mainly focusing on their ability to affect the population of CD4+FoxP3+ regulatory T cells (Treg), and in increasing IL-10 expression. Mouse PP cells were stimulated with live probiotic lactobacilli and the immunological profile was investigated by flow cytometry. We found that only certain probiotic strains had the potential to induce Treg activation and IL-10 expression. In addition, we could also show that carefully selected combinations of strains were confirmed to have synergistic potential in induction of IL-10 expressing Tregs. We also observed a correlation between in vitro data and the therapeutic potential in vivo, using a mouse model of Multiple Sclerosis. This work present a novel method for designing a probiotic mixture with optimal therapeutic potential for the treatment of patients with autoimmune diseases, and MS in particular. (Less)
Popular Abstract
The task of finding probiotic bacteria with high therapeutic potential- like looking for a needle in a haystack.

Probiotics are defined as microorganisms with beneficial effects for the host’s well-being. Each probiotic strain can colonise our intestine where they can work in unique ways to increase health. Some strains have even been shown to have the ability to decrease disease symptoms in an animal model of Multiple Sclerosis (MS). MS is an autoimmune disease where the T lymphocytes of the immune system attack the conductive myelin sheet surrounding the nerves in the central nervous system (CNS). Patients with MS, and also other autoimmune diseases, many times also have intestinal problems thought to be caused by a “leaky gut” and... (More)
The task of finding probiotic bacteria with high therapeutic potential- like looking for a needle in a haystack.

Probiotics are defined as microorganisms with beneficial effects for the host’s well-being. Each probiotic strain can colonise our intestine where they can work in unique ways to increase health. Some strains have even been shown to have the ability to decrease disease symptoms in an animal model of Multiple Sclerosis (MS). MS is an autoimmune disease where the T lymphocytes of the immune system attack the conductive myelin sheet surrounding the nerves in the central nervous system (CNS). Patients with MS, and also other autoimmune diseases, many times also have intestinal problems thought to be caused by a “leaky gut” and gut inflammation that might be connected to their autoimmune disorder.

After finding the link between autoimmune disease and the gut, there has been a lot of research on how to heal the intestine in hopes to also relieve symptoms in patients with autoimmune disease. Scientists have shown that probiotic bacteria can decrease these inflammatory processes through still pretty unknown ways. What is known is that some strains have ability to heal a “leaky gut”, and also activate an important member of the immune system; a T lymphocyte subset called the regulatory T cells (Tregs). These cells have the important task to directly or indirectly, through the release of molecules called cytokines, message the cells causing inflammation to “calm down” and stop being over-reactive, which can relieve the patient’s symptoms. The problem is that not all probiotic bacteria have the ability to activate these cells, and it proves hard to find the ones that do! It also seems like some probiotic bacteria works together to fight inflammation while other strains don’t like teamwork as much, making it a hard job to compose the most potent probiotic mixtures. A common way to test the anti-inflammatory abilities of probiotics is that mice with MS are fed the bacteria to see if they have ability to decrease disease symptoms and inflammation in the mice.

To separate the wheat from the chaff

We wanted to find a quicker, easier way to look for beneficial effects of a library of newly isolated probiotics before testing their potential to reduce inflammation in animals or humans. We took immune cells from the intestine of healthy mice and stimulated them with probiotics for a day, then we looked at the population of the Treg cells and the amount of anti-inflammatory molecules that they had produced. We took some probiotic strains that looked promising using this “screening” method and validated their therapeutical potential in mice with MS, which seemed promising. This method could prove to be an easier way to separate the wheat from the chaff when it comes to probiotics, and reduce the amount of animals needed to find them.



A win-win situation, really!




Advisor: Shahram Lavasani
Masters Degree Project 60 credits in Molecular Biology 2015
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Gullberg, Martina
supervisor
organization
course
MOBT01 20142
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
7758037
date added to LUP
2015-08-10 08:57:10
date last changed
2015-08-10 08:57:10
@misc{7758037,
  abstract     = {There is a great interest in trying to pin-point strain specific effects of probiotics on the immune system. The present study compared desirable immunomodulatory properties of newly isolated, novel probiotic strains of different species in a mouse Peyer’s Patch (PP) cell model in vitro, mainly focusing on their ability to affect the population of CD4+FoxP3+ regulatory T cells (Treg), and in increasing IL-10 expression. Mouse PP cells were stimulated with live probiotic lactobacilli and the immunological profile was investigated by flow cytometry. We found that only certain probiotic strains had the potential to induce Treg activation and IL-10 expression. In addition, we could also show that carefully selected combinations of strains were confirmed to have synergistic potential in induction of IL-10 expressing Tregs. We also observed a correlation between in vitro data and the therapeutic potential in vivo, using a mouse model of Multiple Sclerosis. This work present a novel method for designing a probiotic mixture with optimal therapeutic potential for the treatment of patients with autoimmune diseases, and MS in particular.},
  author       = {Gullberg, Martina},
  language     = {eng},
  note         = {Student Paper},
  title        = {Predicting in vivo therapeutic efficacy of probiotics in a mouse model of Multiple Sclerosis, based on a novel in vitro Peyer’s Patch cell culture system},
  year         = {2015},
}