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Microorganisms Create "Leaky Gut"
There is powerful evidence that microorganisms create "leaky gut"
syndrome.
Microorganisms are associated with leaky gut in both animal and human
models.
This comes as no surprise to the those who follow the SCD diet and have had it heal their gut. Many SCD veterans see their allergies resolve and can tolerate foods that they previously could not. Most of them who have never read research studies on the topic suspected microorganisms as the culprits. The positive changes can be attributed to SCD's elimination of pathogenic microorganisms. Why then, hasn't the diet healed the leaky gut of every child who implements SCD? We now believe it us because parents frequently made the mistake of introducing advanced foods in the beginning stages of the diet. Such foods cannot be properly absorbed by a damaged gut and remain there undigested, providing nourishment for pathogenic microorganisnms Despite the fact that many improvements take place, the children's "leaky gut" did not heal completely when bad gut bacteria consumed the undigested food and were able to survive and reproduce. We recently revised our website to caution about advanced foods. To that end, we also assembled the following collection of articles in order to prevent parents from making the mistake of introducing advanced foods too soon. These articles validate our concern over the role of microorganisms in "leaky gut" syndrome.
View this article in PubMed * Riordan SM, * McIver CJ, * Thomas DH, * Duncombe VM, * Bolin TD, * Thomas MC. Dept. of Gastroenterology, Prince of Wales Hospital, Sydney, Australia. BACKGROUND: The influence of luminal bacteria on small-intestinal permeability has not been fully assessed. This study addressed this issue. METHODS: Thirty-four subjects (mean age 64 years; range 22-95 years) were investigated for possible small-intestinal bacterial overgrowth (SIBO) with culture of a small-intestinal aspirate. A lactulose/mannitol small-intestinal permeability test was performed, small-intestinal histology assessed and serum vitamin B12 concentrations measured in all subjects. Permeability was also assessed in a control group of 34 asymptomatic volunteers. RESULTS: Urinary lactulose/mannitol ratios were significantly increased in subjects with SIBO with colonic-type flora (P < 0.0005), even in the absence of villous atrophy. Urinary lactulose/mannitol ratios were increased in this group due to significantly increased urinary lactulose concentrations (P < 0.0005) rather than reduced urinary mannitol levels, after correcting for inter-subject variations in renal function. Counts of intraepithelial lymphocytes of CD8 phenotype were significantly increased in this group (P = 0.003). Although a significant correlation was found between intraepithelial lymphocyte counts and small-intestinal permeability overall (P < 0.002), these counts were not significantly different in subjects with SIBO with colonic-type flora whose permeability values were < or = > 0.028, the upper limit of normal in asymptomatic controls. Serum vitamin B12 concentrations did not differ significantly between groups (P > 0.5). Ageing did not independently influence small-intestinal permeability (P > 0.5). CONCLUSIONS: Small-intestinal permeability is increased in subjects with SIBO with colonic-type bacteria. This effect is independent of ageing and not mediated by vitamin B12 deficiency. Although counts of intraepithelial lymphocytes of CD8 phenotype are increased in this disorder, it is also unlikely that these cells play an important causative role in this process. Routine light microscopic assessment underestimates the prevalence of small-intestinal functional disturbance in this disorder. PMID: 9200287 [PubMed - indexed for MEDLINE]
Brief explanation of the following research article: Interleukin-10 gene-deficient mice are a special breed of mice that develop intestinal inflammation and a leaky gut. However, in a luminally sterile environment devoid of microorganisms, they will avoid getting a leaky gut or intestinal inflamation.
1: Inflamm Bowel Dis. 1999 Nov;5(4):262-70. * Madsen KL, * Malfair D, * Gray D, * Doyle JS, * Jewell LD, * Fedorak RN. Department of Medicine, University of Alberta, Edmonton, Canada. The normal intestinal epithelium provides a barrier relatively impermeable to luminal constituents. However, patients with inflammatory bowel disease experience enhanced intestinal permeability that correlates with the degree of injury. IL-10 gene-deficient mice were studied to determine whether increased intestinal permeability occurs as a primary defect before the onset of mucosal inflammation or is secondary to mucosal injury. At 2 weeks of age, IL-10 gene-deficient mice show an increase in ileal and colonic permeability in the absence of any histological injury. This primary permeability defect is associated with increased mucosal secretion of interferon-gamma and tumor necrosis factor-alpha, and does not involve an increase in nitric oxide synthase activity. Colonic permeability remains elevated as inflammation progresses, while ileal permeability normalizes by 6 weeks of age. IL-10 gene-deficient mice raised under germ-free conditions have no inflammation, and demonstrate normal permeability and cytokine levels. This data suggests that the intestinal permeability defect in IL-10 gene-deficient mice occurs due to a dysregulated immune response to normal enteric microflora and, furthermore, this permeability defect exists prior to the development of mucosal inflammation. PMID: 10579119 [PubMed - indexed for MEDLINE]
Below are several definitions to clarify the following research article:
Intestinal intraepithelial lymphocytes (IELs) Intestinal intraepithelial lymphocytes (IELs) make up a vast, but poorly understood population of lymphocytes. Located between epithelial cells that line the gut, they may provide a first line of defense against invading pathogens.
Campylobacter enteritis Campylobacter enteritis is an infection in the small intestine caused by Campylobacter jejuni, a type of bacteria. Brief explanation of the following research article: Patients who developed an acute case of Campylobacter enteritis were compared to people who did not have any digestive symptoms(asymptomatic controls). They had significantly higher levels of gut permeability, as assessed by the lactulose/mannitol ratio. This shows that bacterial infections are capable of increasing the gut permeability.
http://gut.bmj.com/cgi/content/abstract/47/6/804
Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome a Division of Gastroenterology, University Hospital Nottingham, Nottingham, UK, b Department of Pathology, University Hospital Nottingham, Nottingham, UK, c Department of Public Health Medicine, University Hospital Nottingham, Nottingham, UK Correspondence to: Dr R C Spiller, Division of Gastroenterology, C Floor, South Block, University Hospital, Nottingham NG7 2UH, UK. robin.spiller@nottingham.ac.uk Accepted for publication 22 June 2000 BACKGROUND AND AIMS---Post-dysenteric irritable bowel syndrome (PD-IBS) develops in up to 25% of patients following Campylobacter enteritis. Our aim was to define the pathological basis of this subgroup of IBS. METHODS---Twenty one patients (group 1) underwent serial rectal biopsy and gut permeability testing following acute Campylobacter enteritis as did 10 PD-IBS patients (group 2) and 12 asymptomatic controls. RESULTS---In group 1, enteroendocrine cell (EC) numbers were markedly increased initially and at six and 12 weeks (p<0.001) compared with controls. Gut permeability, as assessed by the lactulose/mannitol ratio, was significantly elevated, initially and at 12 weeks (p<0.005). CD3, CD4, and CD8 lymphocyte counts in the lamina propria and intraepithelial lymphocytes (IEL) were significantly increased initially compared with controls. At visit 1, EC numbers were positively correlated with CD3 counts (r=0.6, p=0.01). At one year, seven subjects (five with persistent loose stools) had rectal biopsies which showed significantly elevated EC, CD3, and IEL counts. In group 2, EC and IEL counts were significantly increased compared with controls (p<0.001), as was gut permeability (p<0.01). CONCLUSION---Increased EC, T lymphocytes, and gut permeability are acute changes following Campylobacter enteritis which can persist for more than a year and may contribute to PD-IBS.
View this article in PubMed 1: Gastroenterology. 2002 Nov;123(5):1607-15.Click here to read Links Erratum in: Gastroenterology 2003 Jan;124(1):275. El Asmar Rahzi [corrected to El Asmar Ramzi]. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. * El Asmar R, * Panigrahi P, * Bamford P, * Berti I, * Not T, * Coppa GV, * Catassi C, * Fasano A. Department of Pediatrics and Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. BACKGROUND & AIMS: Enteric infections have been implicated in the pathogenesis of both food intolerance and autoimmune diseases secondary to the impairment of the intestinal barrier. On the basis of our recent discovery of zonulin, a modulator of small-intestinal tight junctions, we asked whether microorganisms might induce zonulin secretion and increased small-intestinal permeability. METHODS: Both ex vivo mammalian small intestines and intestinal cell monolayers were exposed to either pathogenic or nonpathogenic enterobacteria. Zonulin production and changes in paracellular permeability were monitored in Ussing chambers and micro-snapwells. Zonula occludens 1 protein redistribution after bacteria colonization was evaluated on cell monolayers. RESULTS: Small intestines exposed to enteric bacteria secreted zonulin. This secretion was independent of either the species of the small intestines or the virulence of the microorganisms tested, occurred only on the luminal aspect of the bacteria-exposed small-intestinal mucosa, and was followed by a decrease in small-intestinal tissue resistance (transepithelial electrical resistance). The transepithelial electrical resistance decrement was secondary to the zonulin-induced tight junction disassembly, as also shown by the disengagement of the protein zonula occludens 1 protein from the tight junctional complex. CONCLUSIONS: This zonulin-driven opening of the paracellular pathway may represent a defensive mechanism, which flushes out microorganisms and contributes to the host response against bacterial colonization of the small intestine. PMID: 12404235 [PubMed - indexed for MEDLINE] Yogurt is also very helpful for the leaky gut:
View this article in PubMed * Heyman M, * Terpend K, * Menard S. INSERM EMI 0212, Faculte Necker-Enfants malades, Paris, France. Non-live probiotic bacteria and their fermentation products can be used in milk-based formula intended for healthy infants. The effects of a milk formula fermented with Bifidobacterium breve and Streptococcus thermophilus and heated/dehydrated to inactivate the micro-organisms have been reported over the last few years to decrease the intestinal permeability to macromolecules in experimental animals in vivo and more recently to down-regulate inflammatory condition in vitro. Feeding guinea-pigs with such dehydrated fermented milk reinforced the intestinal barrier resistance to food proteins (HRP, beta-lactoglobulin). In addition, the products secreted by bacteria were capable of inhibiting the lipopolysaccharide (LPS)-induced TNF-alpha secretion by human peripheral mononuclear blood cells. The active secretion products were resistant to digestive enzymes and their anti-inflammatory properties were preserved after transepithelial transport across the filter-grown intestinal epithelial cell line, especially in inflammatory conditions. The binding of LPS to monocytes as well as NFkappaB nuclear translocation leading to pro-inflammatory cytokine transcription were inhibited by bacteria-culture supernatants. CONCLUSION: B. breve and S. thermophilus used as non-live micro-organisms in fermented infant formula seem to induce a reduction in macromolecular absorption and release metabolites exerting an anti-TNF-alpha effect, which persists after intestinal transport. Thus, specific lactic acid bacteria and their metabolites seem to affect positively the intestinal function. PMID: 16214764 [PubMed - indexed for MEDLINE] |