Vitamin D 'Deficiency' - Bacterial Etiology
Vitamin D proponents use a disease deficiency model to explain low levels of 25(OH)D. Their hypothesis states low 25(OH)D causes chronic diseases; however, a pathogenesis has not been elucidated. Low serum 25(OH)D in the presence of disease can also be explained with a dysregulated vitamin D metabolism model. This hypothesis proposes that low vitamin D is the consequence of a chronic inflammatory process caused by persistent infection.
The bacterial pathogenesis theorizes that intracellular bacteria cause abnormal vitamin D endocrine function, resulting in low vitamin D. Specifically, cell wall deficient (CWD) bacteria invade nucleated cells and use strategies to avoid destruction. Excess 1,25(OH)2D is produced in an effort to up-regulate the VDR to transcribe AMPs; and 25(OH)D is rapidly metabolized in the process, resulting in a low serum level.
The resulting elevated 1,25(OH)2D causes chronic, systemic inflammation and its accompanying symptoms. Gerald J Domingue, Professor Emeritus of Tulane University School of Medicine commented, "This might translate into an etiology for chronic inflammatory diseases, when the stressed bacteria increase in numbers and overwhelm the normal biological functions of the host." [1] Gabriel Nunez, M.D., Professor of Pathology at the University of Michigan Medical School, was quoted in the university newsletter, "In our study, the presence of bacterial microbes inside the cell is what triggers the immune response." [2]
In 2007 French researchers observe that the presence of pathogenic invasive bacteria could be the link between an innate immune response to invasive bacteria and the development of the inflammation. [3] Dr. Siobhan O'Connor, assistant to the director of the National Center for Infectious Diseases, stated, "The epidemiologic, clinical, and pathologic features of many chronic inflammatory diseases are consistent with a microbial cause. Infectious agents likely determine more cancers, immune-mediated syndromes, neurodevelopmental disorders, and other chronic conditions than currently appreciated." [4]
A known effect of vitamin D is suppression of the immune system. [5] In a study of a pro-inflammatory molecule, lipopolysaccharide (LPS), Lemire found elevated 25(OH)D reduced the inflammatory cascade. [6] Low levels (below 30ng/ml) failed to inhibit the LPS inflammatory cascade but higher levels (30ng/ml) inhibited inflammatory signaling. The highest levels of inflammatory inhibition occurred at 50ng/ml. 25(OH)D can also be indirectly immuno-suppressive by being converted to excess 1,25(OH)2D.
A 2007 study concluded, "On the whole, vitamin D confers an immunosuppressive effect." [7] Theoretically, immune system suppression allows parasitic microbes to persist and proliferate in host phagocytes, successfully compete for nutritional resources, and displace commensal organisms from their niche. [8]
References:
1. Domingue GJ. Demystifying pleomorphic forms in persistence and expression of disease: Are they bacteria, and is peptidoglycan the solution? Discov Med. Sep 2010;10(52):234-46. 2. Rueter A. Microbes start immune response by sneaking inside cells. University of Michigan Health System. Apr 16, 2007. http://www2.med.umich.edu/prmc/media/newsroom/details.cfm?ID=577. Accessed May 8, 2013. 3. Rolhion N, Darfeuille-Michaud A. Adherent-invasive Escherichia coli in inflammatory bowel disease. Inflamm Bowel Dis. Oct 2007;13(10):1277-83. 4. O'Connor SM, Taylor CE, Hughes JM. Emerging infectious determinants of chronic diseases. Emerg Infect Dis. Jul 2006;12(7):1051-7. 5. Zhang Y, Leung DY, Richers BN, et al. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol. Mar 2012;188(5):2127-35. 6. Lemire J. 1,25-Dihydroxyvitamin D3--a hormone with immunomodulatory properties. Z Rheumatol. 2000;59 Suppl 1:24-7. 7. Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis. Sep 2007;66(9):1137-42. 8. Domingue G, Turner B, Schlegel JU. Cell-wall deficient bacterial variants in kidney tissue. Detection by immunofluorescence. Urology. Mar 1974;3(3):288-92.
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