22 February, 2006
Some interesting work is being done in the area of leaky gut syndrome. It is beginning to be acknowledged now in bona fide research circles that bacterial translocation may be associated with the development of auto-immune diseases. Although medical science is only just beginning to catch up with the naturopaths in this regard (never thought I'd say something like that!) it is becoming clear that such problems are not all due to Candida overgrowth up the small intestine. It now seems far more likely that many of these food sensitivity and autoimmune conditions are due to overgrowth with good old E. coli. Certainly, the previously quoted cross-reaction between the lac7 gene of E. coli and the antibodies associated with lupus supports this case.
See below for one piece of the puzzle.
http://www.childrenshospitalla.org/body.cfm?id=75&action=detail&ref=131
Michelle M. Pietzak, MD
Assistant Professor
Research Interest
Bacterial Translocation of the Gastrointestinal Tract
Phone
(323) 669-2181
Fax
(323) 664-0718
Email
mpietzak@chla.usc.edu
Escherichia coli K1 Interactions with Intestinal Epithelium
Dr. Pietzak's research focuses primarily on the mechanisms by which E. coli is able to translocate across the intestinal epithelium. This pathogen is then able to disseminate systemically, causing sepsis and meningitis. E. coli is a leading cause of severe bacterial infections in premature infants, neonates, immunocompromised hosts, and children with central lines and primary intestinal diseases. Enteric pathogens may also serve as a trigger to the development of autoimmune gastrointestinal diseases, such as celiac disease and Crohn's disease, in genetically susceptible individuals. E. coli strain RS218 is the clinical isolate from the cerebrospinal fluid of an infant with E. coli meningitis. Dr. Pietzak's research focuses on investigating the mechanisms by which RS218 is able to penetrate the intestinal epithelial barrier. Enteric bacteria may contribute to the development of inflammatory bowel diseases by directly damaging the intestinal mucosa or by the translocation of whole bacteria or bacterial products. Via translocation, specific microbial components (such as E. coli OmpC) can gain access to the lamina propria and potentially activate or regulate adaptive immune responses involved in intestinal inflammation. Adherent and invasive E. coli strains have recently been reported to be associated with both Crohn's disease and ulcerative colitis. In addition, antibodies to numerous E. coli antigens, such as OmpC and S-fimbriae, have been found with increased frequency in patients with inflammatory bowel disease and immune-deficient states. Translocation of bacteria across the intestinal epithelial barrier first involves binding and invasion of the enterocyte. E. coli K1, a common enteric organism, is able to translocate the gut barrier and disseminate, causing meningitis in susceptible hosts. Dr. Pietzak has identified two virulence factors in E. coli K1, which are important in E. coli-small bowel enterocyte interactions: the S-fimbriae operon for binding and gene ibeA for invasion. Deletion of the S-fimbria operon abrogates the ability of E. coli K1 to bind, invade and translocate intestinal epithelium in vitro and in neonatal rats in vivo. Deletion of ibeA renders E. coli K1 less effective at invasion in vitro, and leads to less dissemination, sepsis and meningitis in the neonatal rat. Complementation with ibeA restores the invasive phenotype. Furthermore, the E. coli K1 parent strain induces a particular type of small bowel damage located at the villous tips where bacteria are in direct contact. The mechanism of this damage is the subject of ongoing research, which will utilize various techniques to study apoptosis of the intestinal epithelial cell in response to E. coli K1, both in vitro and in vivo. The contributions of S-fimbriae and ibeA to this particular type of small bowel injury will be examined. Further investigations regarding the importance of S-fimbriae and gene ibeA in E. coli K1 bacterial translocation may lead to novel therapeutics in both the treatment and prevention of inflammatory bowel disease.
See below for one piece of the puzzle.
http://www.childrenshospitalla.org/body.cfm?id=75&action=detail&ref=131
Michelle M. Pietzak, MD
Assistant Professor
Research Interest
Bacterial Translocation of the Gastrointestinal Tract
Phone
(323) 669-2181
Fax
(323) 664-0718
mpietzak@chla.usc.edu
Escherichia coli K1 Interactions with Intestinal Epithelium
Dr. Pietzak's research focuses primarily on the mechanisms by which E. coli is able to translocate across the intestinal epithelium. This pathogen is then able to disseminate systemically, causing sepsis and meningitis. E. coli is a leading cause of severe bacterial infections in premature infants, neonates, immunocompromised hosts, and children with central lines and primary intestinal diseases. Enteric pathogens may also serve as a trigger to the development of autoimmune gastrointestinal diseases, such as celiac disease and Crohn's disease, in genetically susceptible individuals. E. coli strain RS218 is the clinical isolate from the cerebrospinal fluid of an infant with E. coli meningitis. Dr. Pietzak's research focuses on investigating the mechanisms by which RS218 is able to penetrate the intestinal epithelial barrier. Enteric bacteria may contribute to the development of inflammatory bowel diseases by directly damaging the intestinal mucosa or by the translocation of whole bacteria or bacterial products. Via translocation, specific microbial components (such as E. coli OmpC) can gain access to the lamina propria and potentially activate or regulate adaptive immune responses involved in intestinal inflammation. Adherent and invasive E. coli strains have recently been reported to be associated with both Crohn's disease and ulcerative colitis. In addition, antibodies to numerous E. coli antigens, such as OmpC and S-fimbriae, have been found with increased frequency in patients with inflammatory bowel disease and immune-deficient states. Translocation of bacteria across the intestinal epithelial barrier first involves binding and invasion of the enterocyte. E. coli K1, a common enteric organism, is able to translocate the gut barrier and disseminate, causing meningitis in susceptible hosts. Dr. Pietzak has identified two virulence factors in E. coli K1, which are important in E. coli-small bowel enterocyte interactions: the S-fimbriae operon for binding and gene ibeA for invasion. Deletion of the S-fimbria operon abrogates the ability of E. coli K1 to bind, invade and translocate intestinal epithelium in vitro and in neonatal rats in vivo. Deletion of ibeA renders E. coli K1 less effective at invasion in vitro, and leads to less dissemination, sepsis and meningitis in the neonatal rat. Complementation with ibeA restores the invasive phenotype. Furthermore, the E. coli K1 parent strain induces a particular type of small bowel damage located at the villous tips where bacteria are in direct contact. The mechanism of this damage is the subject of ongoing research, which will utilize various techniques to study apoptosis of the intestinal epithelial cell in response to E. coli K1, both in vitro and in vivo. The contributions of S-fimbriae and ibeA to this particular type of small bowel injury will be examined. Further investigations regarding the importance of S-fimbriae and gene ibeA in E. coli K1 bacterial translocation may lead to novel therapeutics in both the treatment and prevention of inflammatory bowel disease.
