Team:SDU-Denmark

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Revision as of 20:10, 30 August 2012

iGEM TEAM ::: SDU-DENMARK courtesy of NIAID

Novel approach in the fight against obesity: modulating gut microbiota by probiotic inulin producing bacteria

Obesity is associated with a low-grade inflammatory response, which is, among other things, triggered by bacterial plasma lipopolysaccharide (LPS). A high-energy diet, increases the amount of LPS-producing gut microbiota, and increased LPS levels has been observed in obese individuals. By inducing changes in the gut microbiota by prebiotics like inulin, it’s possible to decrease the plasma LPS level. This is associated with the stimulation of bifidobacterial growth. We have designed a novel approach to address this issue of plasma LPS, by probioticly induce changes in the gut flora by genetically modifying a bacteria to produce plant originated inulin. We cloned the two genes encoding sucrose:sucrose fructosyltransferase (SST) and fructose:fructose fructosyltransferase (FFT) from the Jerusalem artichoke into a bacterial chassi. The probiotic bacteria are then introduced into the gut via yoghurt and will produce inulin by using sucrose as acceptor molecules.

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-	<h2>Novel approach to carbohydrate intake restriction using bacterial machines as sucrose converters</h2>
+	<h2>Novel approach in the fight against obesity: modulating gut microbiota by probiotic inulin producing bacteria</h2>
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-	 The modern diet is rich in carbohydrates and though increasing awareness about the health problems related, obesity is still the sixth most important risk factor contributing to the overall burden of disease worldwide and therefore a large burden on society. For reasons unknown, risks like cardiovascular disease, type 2 diabetes and different types of cancers, that all can be related to obesity, do not seem to motivate a healthy diet in modern society.
+	 Obesity is associated with a low-grade inflammatory response, which is, among other things, triggered by bacterial plasma lipopolysaccharide (LPS).  A high-energy diet, increases the amount of LPS-producing gut microbiota, and increased LPS levels has been observed in obese individuals. By inducing changes in the gut microbiota by prebiotics like inulin, it’s possible to decrease the plasma LPS level. This is associated with the stimulation of bifidobacterial growth. We have designed a novel approach to address this issue of plasma LPS, by probioticly induce changes in the gut flora by genetically modifying a bacteria to produce plant originated inulin. We cloned the two genes encoding sucrose:sucrose fructosyltransferase (SST) and fructose:fructose fructosyltransferase (FFT) from the Jerusalem artichoke into a bacterial chassi. The probiotic bacteria are then introduced into the gut via yoghurt and will produce inulin by using sucrose as acceptor molecules.
-In our project we approach this problem from a new angle. Instead of changing the diet, we take a look at the mechanisms that regulate carbohydrate uptake from our daily diet. We will focus on conversion of sugars into fibers, namely inulin, that the human body is unable to digest. Apart from being indigestible inulin possesses interesting properties as a prebiotic. Inulin affect the gut microbiota by promoting ”helpful” bacteria, like bifidobacteria. Intake of short-chain inulin has been proven to lead to a significant decrease in food intake, body weight gain and fat mass development in rodents.
-The ultimate goal of the project will be to construct a probiotic microorganism, capable of producing inulin fibers and able to survive in the human gut for short periods of time. We will clone the genes coding for the plant enzymes Fructan:fructan 1-fructosyltransferase (1-FFT) and sucrose sucrose 1-fructosyltransferase (1-SST) that together make up the synthesis pathway of plant inulin in Helianthus tuberosus (degree of polymerization: 30-150) or a bacterial version of inulin synthase, possibly from Lactobacillus Reuteri (degree of polymerization: 20-10.000). Furthermore, we will look into other mechanisms that could regulate sugar uptake, like adding a cellulose synthase to our construct as well. Which would further increase the beneficial factor of the microorganism, by removing larger amounts of sugar from the diet, and contributing cellulose to the intestine which among other things, have a preventive effect on the development of colon cancer.
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