Download Tisdag 17 jan

Presentations of examen projects in
zoophysiology Spring 2011
Library 1st floor
Thursday September 30
12.15
Mattias Bergentall (Human physiology, 45 hp)
Regulation of small intestinal permeability in mice by gut
microbes
Opponent: Lars Niklasson
ca 13.15
Reza Motalleb (Human physiology, 60 hp)
The biological response of stem cells grown on
electrospun nanofiber scaffolds
Opponent: Lisa Jönsson Bergman
Abstracts
Regulation of small intestinal permeability in mice by gut microbes
Mattias Bergentall
Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg
Laboratory, Dept. Molecular & Clinical Medicine, GU
During later years, the impact of traditionally-seen non-infectious microbes has emerged as
more pronounced than expected with effects believed to range from shaping the immune system
(according to the hygiene hypothesis) to alterations in the host metabolism (vitamin synthesis,
energy uptake) and development of the brain. Despite the fact that germ free animals (reared in
an environment completely absent of all bacteria and fungi) has been used in research for
several decades, the new culture-independent methods to investigate the composition of
microbial communities (e.g. in the intestine and other mucosal surfaces and on the skin as well
as in free nature) has enabled researchers to gain substantial insight into the microbial world
that has been largely neglected. It is now established that the gut microbiota is composed of up
to 1000 different bacterial species, their viruses and different fungi.
Intestinal permeability is part of basic physiology and dysregulation is implicated in
numerous human diseases (inflammatory bowel diseases (IBD), allergic reactions, diarrhea,
asthma, low grade metabolic inflammation, etc.), furthermore it is used as an indicator of well
being in farmed fish. Permeability, the flow of substances across a porous wall, in the intestine
can mainly be divided in two fundamentally different parts; transcellular (through cells, across
both apical and basolateral cell membrane) and paracellular (in the spaces between cells). The
former is based on simple diffusion (small uncharged molecules) and endocytosis or carriermediated transport whereas the latter is regulated ultimately by structures that connect proximal
cells to each other (tight junctions, TJ’s).
Tight junctions are big multi protein complexes consisting of different transmembrane
proteins which form the actual cell-cell junction and adapter proteins that connect the
transmembrane proteins to the cytoskeleton inside each cell, which is necessary to create the
strong physical strength needed to resist shear forces and keep an epithelial lining intact. In all,
some 30 proteins are involved in forming TJ’s and it is thought that the protein composition
regulates the tightness of the cell-cell junction. Another way of regulating the TJ tightness is by
contraction of the acto-myosin ring to which the TJ’s are attached.
Germ free (GF) mice have been shown to be protected from diet induced obesity, which is in
part caused by a metabolic inflammation probably driven by endotoxin (lipopolysaccharide)
derived from the gut microbiota, and from inflammatory bowel diseases which are characterized
partly by an increased intestinal permeability. We therefore hypothesized that GF mice could
have obtained these protective traits, at least partly, by having a reduced intestinal permeability.
We have previously seen that two important TJ proteins are differentially expressed in
conventionally raised (CR) mice compared with GF. In this report, intestinal permeability was
investigated, and found to be higher in CR mice, by measuring the flux of a fluorescent marker
across the epithelium in Ussing chambers. Once this is established, future work will include
finding the responsible microbes, in order to eliminate or reduce them, which could potentially
reduce IBD symptoms and obesity if administered to patients.