13 January, 2006
Auto-immune diseases and Leaky gut syndrome.
The model for the cause of auto-immune diseases (and there are at least 130 of them) is quite straight forward. Firstly there has to be a genetic predispostion. This simply means that a gene is present (or more precisely a form of a normal gene) that is recognised by the antibodies that cause the disease. Thus in Rheumatoid Arthritis the RA gene encodes for a particular variant of a normal structural protein in the joints. But the presence of the gene alone is not sufficient to cause the disease. Genetically engineered mice that have the human RA gene in their DNA and have been delivered by aseptic caesarian and kept germ-free do not develop the disease. But if bacteria are introduced to their gut they develop arthritis.
But how do the bacteria trigger the formation of the antibodies? Firstly it needs to be understood that the inside of intestines are contiguous with the outside of our bodies and are, technically speaking, not on our "insides". Our true insides lie the other side of the intestinal wall and bacteria are looking for ways to make that journey. There are more than 10 mechanisms that have been identified whereby various bacteria facilitate translocation of themselves into our true interior. For example, we produce a protein called zonulin which we use to regulate the permeability of our intestinal wall. It operates on the tight junctions (the so-called "zonula occludens") which it opens. Normally only small molecules such as simple sugars, minerals and amino acids, etc., are transported through or diffuse through the cell walls. Interestingly, people with celiac disease are genetically programmed to produce 15 times too much zonulin and this makes their intestines permeable to large molecules such as gluten. Some bacteria can produce a protein that mimics zonulin, in fact the last 20 amino acids are identical. This bacterial "zonulin" opens the tight junctions and the bacterium can slip on through. Once on the inside, it provokes an immune response. The bacterial cells are killed and their contents are spilled out. Inside, the bacteria have many structures that resemble our own and when antibodies are made to these, these same antibodies can react with any human structures that they "recognise".
RA and SLE (lupus) both involve overgrowth of the small intestine with E. coli and perhaps other Gram negative bacteria are involved in other conditions. Yersinia is thought to be involved in Ankylosing Spondylitis, for example.
The antibodies of SLE have been found to cross-react with the lac7 gene in E. coli, suggesting that this is the trigger.
The model for the cause of auto-immune diseases (and there are at least 130 of them) is quite straight forward. Firstly there has to be a genetic predispostion. This simply means that a gene is present (or more precisely a form of a normal gene) that is recognised by the antibodies that cause the disease. Thus in Rheumatoid Arthritis the RA gene encodes for a particular variant of a normal structural protein in the joints. But the presence of the gene alone is not sufficient to cause the disease. Genetically engineered mice that have the human RA gene in their DNA and have been delivered by aseptic caesarian and kept germ-free do not develop the disease. But if bacteria are introduced to their gut they develop arthritis.
But how do the bacteria trigger the formation of the antibodies? Firstly it needs to be understood that the inside of intestines are contiguous with the outside of our bodies and are, technically speaking, not on our "insides". Our true insides lie the other side of the intestinal wall and bacteria are looking for ways to make that journey. There are more than 10 mechanisms that have been identified whereby various bacteria facilitate translocation of themselves into our true interior. For example, we produce a protein called zonulin which we use to regulate the permeability of our intestinal wall. It operates on the tight junctions (the so-called "zonula occludens") which it opens. Normally only small molecules such as simple sugars, minerals and amino acids, etc., are transported through or diffuse through the cell walls. Interestingly, people with celiac disease are genetically programmed to produce 15 times too much zonulin and this makes their intestines permeable to large molecules such as gluten. Some bacteria can produce a protein that mimics zonulin, in fact the last 20 amino acids are identical. This bacterial "zonulin" opens the tight junctions and the bacterium can slip on through. Once on the inside, it provokes an immune response. The bacterial cells are killed and their contents are spilled out. Inside, the bacteria have many structures that resemble our own and when antibodies are made to these, these same antibodies can react with any human structures that they "recognise".
RA and SLE (lupus) both involve overgrowth of the small intestine with E. coli and perhaps other Gram negative bacteria are involved in other conditions. Yersinia is thought to be involved in Ankylosing Spondylitis, for example.
The antibodies of SLE have been found to cross-react with the lac7 gene in E. coli, suggesting that this is the trigger.
