Bacterial Cytotoxins refer to the cytolethal distending toxin, subunit B (CdtB) that is released by Escherichia coli, Salmonella, Shigella and Campylobacter jejuni. Utilizing subunits A and C, gram-negative bacteria can bind to human cells, allowing CdtB to infiltrate the cell. Inside the cell, CdtB contributes to cytoskeletal damage, which may induce apoptosis (cell death). CdtB is the first bacterial toxin known to act in the nucleus of a target cell.
Associated With:
- Irritable bowels
- SIBO
- Gut dysbiosis
- Chronic functional bowel changes
- Localized aggressive periodontitis
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Cyrex Array 22 measures IgA, IgG and IgM antibodies against bacterial cytotoxins and cytoskeletal proteins in human blood. This is based on the scientific fact that bacteria from the colon move up to the upper gut, and their concentrations become elevated. By producing cytotoxins, these bacteria affect the delicate environment of the small intestine, and then gain entry into the cell, where, by binding to the cellular DNA, they induce apoptosis (cell death). They then find their way to the submucosa, regional lymph nodes, and into the circulation. Immune response against the bacterial cytotoxins may result in the production of IgA, IgM and IgG antibodies against them.
Due to the antigenic similarity between E. coli, Salmonella, Shigella toxins, Campylobacter jejuni and human cytoskeletal proteins such as vinculin and talin, these antibodies cross-react with the cytoskeletal proteins, causing depolymerization of and release of these proteins from the epithelial cells, with subsequent antibody production against the cytoskeletal proteins vinculin, talin, and actinin. These IgA, IgM and IgG antibodies against bacterial cytotoxins and cytoskeletal proteins are detected in the blood with high accuracy and reproducibility. Thus, bacterial over-growth can be an instigator of extra-intestinal autoimmunity (autoimmune reactivity outside of the gastrointestinal tract).
Cytotoxins are lethal xenobiotics released by commensal coliform bacteria. Bacterial cytotoxins can destroy epithelial cells of the intestinal barrier. Therefore, Cyrex also assesses antibodies to cytoskeletal proteins. Once this epithelial cell damage occurs, bacterial cytotoxins can freely enter circulation. Like systemic lipopolysaccharides, when bacterial cytotoxins enter the blood stream, they produce chronic inflammation and can permeate the blood brain barrier.
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Bacteria such as E. coli, Salmonella, Shigella and C. jejuni, are members of the bacteria that participate in diseases that involve the disruption of a mucosal or epithelial layer.
By producing cytotoxins, these bacteria affect the delicate environment of the small intestine, and then gain entry into the cell, where by binding to the cellular DNA, they induce apoptosis. They find their way to the submucosa, regional lymph nodes, and into circulation where the immune system responds by producing antibodies against them. Indeed, in vitro studies have shown that human epithelial cells are native targets of the CdtB expressed by these bacteria.
Cell infiltration by CdtB induces DNA damage which signals growth arrest at the G2/M (state of cell growth and division) interphase of the cell cycle.
The epithelium is an early line of defense in the oral cavity and the gastrointestinal system against microbial assault.
When damaged, bacteria collectively gain entry into the underlying connective tissue where microbial products can affect processes and pathways culminating in the destruction of the epithelial barrier and the underlying tissue. Antibodies against Bacterial Cytotoxins indicate gut dysbiosis with the potential for causing intestinal barrier damage.
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