Background

Problematics concerning obesity

Obesity is the sixth most important risk factor contributing to the overall burden of disease worldwide, and therefore a large burden on our society. Obesity can lead to a variety of different diseases such as cardiovascular disease, type 2 diabetes, and different types of cancers. (Haslam DW, 2005) (Ya-Ni Yin, 2010)

Causes of obesity

It is not surprising that a high fat and carb diet will increase adipose tissue, since the excess calories have to be stored somewhere. But there are many factors that play a role in obesity, some known and some yet to be discovered. Obesity is associated with a low-grade inflammatory response which is, among other things, triggered by bacterial plasma lipopolysaccharide (LPS). It is shown, that a high fat diet increases the amount of LPS-producing gut microbiota, and an increased LPS level has been observed in obese individuals (Cani, 2011). When an increase in LPS happens, certain markers increase (e.g. adipose tissue F4/80-positive cells, markers of inflammation and liver triglyceride content). Decreasing the plasma LPS level is a potential strategy for fighting obesity. (Patrice D. Cani, 2007)

Our strategy to fight obesity

Figur 1 - Prebiotics such as inulin and fructooligosaccharides (FOS) can induce changes in the gut microbiota. By stimulating these changes in favor of inulin fermenting bacteria, the tight junction proteins, ZO-1 and Occludin, increase In numbers, hence lowering the plasma LPS level and the gut permability. Changing the gut microbiota also leads to secretion of some anorexigenic peptides (PYY, GLP-1 and GLP-2) and one orexigenic peptide (Ghrelin). Theese changes improve obesity and other metabolic disorders associated with obesity. (Cani, 2011)

It has been shown, that by using prebiotics to change the gut microbiota, the tight junction proteins ZO-1 and Occludin is restored and the gut permeability decreased. When changing the gut microbiota with prebiotics (inulin, and Fructooligosaccharides (FOS)) in rodents, it leads to a significant decrease in food intake, body weight gain, and fat mass development. This is associated with the secretion of two anorexigenic peptides, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Also there is a decrease in the orexigenic peptide ghrelin. These peptides modulates food intake and energy usage (Cani, 2011).By applying these prebiotics we stimulate growth of “helpful” bacteria. These bacteria have a lot of different positive effects on host health (figure ??), and is not just a single strain or group. One of the families of bacteria that are considered beneficial for humans is the bifidobacteria which can grow on inulin containing substrates. Inulin and FOS is the prebiotics used to stimulate bifidobacterial growth (Gibson GR, 1995)

Figur 2 – A figure, mapping the number of predominant bacteria in human feces and the harmful/health promoting functions of these. Note that bifidobacteria and lactobacilli is considered health promoting only. (Gibson GR, 1995)

Bifidobacteria produces acetate and lactate which lowers the pH in the intestines, making it hard for other bacteria to survive. Also the bifidobacteria can produce and excrete a metabolic end product that is inhibitory to a variety of pathogenic gram-positive and gram-negative bacteria. They protonate potentially toxic ammonia and amines to make NH4+, that cannot diffuse into the bloodstream thereby lowering the blood ammonia level. They produce vitamins (mainly from the B-group) and enzymes like casein phosphatase and lysozyme. Bifidobacteria works as immunomodulaters and promotes immunological attack against malignant cells. Bifidobacteria is used as a supplement if you are on an antibiotic therapy, to restore normal gut microbiotic flora. (Gibson GR, 1995).
To improve bifidobacterial growth in the gut we want to give them inulin-type fructans. Most bifidobacterial strains ferments fructooligosaccharide (FOS) and inulin, and when they do this in cultures they also reduce numbers of bacteroides, clostrida or coliforms (Gibson GR, 1995).

There have already been made different kinds of weight control pills containing inulin, and inulin is industrially obtained from chicory roots. The way we want to deliver our inulin to the gut microbiota is by making a bacteria that can be eaten (e.g. fermented milk products with pro-biotic lactobacillus) and then travel to the gut where it can produce inulin from sucrose (sucrose is not taken up before the gut either). Another positive aspect of the inulin production is that the bacteria should use a lot of the sugar we eat and convert it into the non-digestible fiber, hence lowering the energy we get from eating sucrose. Since sucrose consists of a fructose and glucose unit, there will be one glucose unit leftover for every added monomer of fructose to the inulin polymer. These glucose units could then be used as an added bonus to produce Cellulose, so that we could get additional fibers in our diet and get rid of the glucose.