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Use of Lactobacillus salivarius

a technology of lactobacillus and salivarius, which is applied in the field of use of lactobacillus salivarius, can solve the problems of destroying host cells and tissue function, and achieve the effects of promoting cellular activation and pathogen destruction, and eliminating the threat of bacterial bacteria

Inactive Publication Date: 2003-09-04
ENTERPRISE IRELAND +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008] Lactobacillus salivarius is a commensal microorganism originally isolated from the microbial flora within the human gastrointestinal tract. The immune system within the gastrointestinal tract cannot have a pronounced reaction to members of this flora as the resulting inflammatory activity would also destroy host cells and tissue function. Therefore, some mechanism(s) exist whereby the immune system can recognise commensal non-pathogenic members of the gastrointestinal flora as being different to pathogenic organisms. This ensures that damage to host tissues is restricted and a defensive barrier is still maintained.
[0052] Thus, UCC118 survives passage through the gastrointestinal tract, modulates the gut flora and is perceived by the mucosal immune system. The influence of this probiotic bacteria in modulating inflammatory responses within the gastrointestinal tract was examined using a murine model of enterocolitis. In addition, we examined the role of Lactobacillus salivarius subsp. salivarius UCC118 in reducing the rate of neoplastic change within the gastrointestinal tract.
[0078] The immune system has a large repertoire of specificities expressed by B and T cells. Some of these specificities will be directed to self-components. Self-recognition is normally controlled by clonal deletion and inactivation of self-reactive lymphocytes. However, there is a constant background of autoimmunity with antibodies to many proteins being found in serum. A breakdown in the self-nonself recognition system results in autoimmunity. When autoimmune disease does occur, the resulting immune response damages the tissue bearing the offending antigen. Immune complex deposition, type II hypersensitivity and cell-mediated reactions are the most important mechanisms by which immunopathological damage occurs. Examples of autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, insulin dependent diabetes mellitus, myasthenia gravis and pernicious anaemia. We have found that Lactobacillus salivarius is an immunomodulatory bacterium. Thus, consumption either as a single component or in combination with other bacteria by patients suffering from autoimmune disease may restrict organ damage and help restore normal body homeostasis.
[0082] The introduction of probiotic organisms is accomplished by the ingestion of the microorganism in a suitable carrier. It would be advantageous to provide a medium that would promote the growth of these probiotic strains in the large bowel. The addition of one or more oligosaccharides, polysaccharides, or other prebiotics enhances the growth of lactic acid bacteria in the gastrointestinal tract (Gibson, G R. Br. J. Nutr. 1998;80 (4):S209-12). Prebiotics refers to any non-viable food component that is specifically fermented in the colon by indigenous bacteria thought to be of positive value, e.g. bifidobacteria, lactobacilli. Types of prebiotics may include those which contain fructose, xylose, soya, galactose, glucose and mannose. The combined administration of a probiotic strain with one or more prebiotic compounds may enhance the growth of the administered probiotic in vivo resulting in a more pronounced health benefit, and is termed synbiotic.

Problems solved by technology

The immune system within the gastrointestinal tract cannot have a pronounced reaction to members of this flora as the resulting inflammatory activity would also destroy host cells and tissue function.

Method used

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  • Use of Lactobacillus salivarius
  • Use of Lactobacillus salivarius
  • Use of Lactobacillus salivarius

Examples

Experimental program
Comparison scheme
Effect test

example 2

[0056] Human Trial with UCC118 in patients with active Crohn's disease.

[0057] Inflammatory bowel disease (EBD) encompasses a number of inflammatory disorders of the gastrointestinal tract, including both Crohn's disease and ulcerative colitis.

[0058] Patients suffering from active Crohn's disease have been treated with UCC118. Briefly, UCC118 was consumed in a fermented milk product for 6 weeks by 22 patients. Microbiological and immunological determinations were made at week 0, week 1, week 3 and week 6. This was not a placebo-controlled trial.

[0059] A number of systemic cytokine levels were measured over the course of feeding. In particular, tumour necrosis factor a (TNF.alpha.), a proinflammatory cytokine that has been implicated in the pathogenesis of many inflammatory disease states, including inflammatory bowel disease. Current therapies for inflammatory bowel disease specifically aim to reduce TNF.alpha. levels (Present D. H., et al. New Eng. J. Med., 1999, 340, 1398). In this...

example 3

[0061] Detailed description of the in vitro demonstration of the mechanisms underlying the anti-inflammatory effects of Lactobacillus salivarius especially subspecies salivarius UCC118.

[0062] A number of methodologies have been utilised for these studies including ELISAs (extracellular protein determination), flow cytometry (intracellular protein determination) and cDNA expression arrays (mRNA expression). In particular, examination of the expression of tumour necrosis factor .alpha. has been targeted, due to its clinical importance, and suppression of the production of this cytokine, following exposure to UCC118, has been noted using all three methodologies.

[0063] Using a transwell assay system, with epithelial cells and peripheral blood mononuclear cells, extracellular cytokine levels were measured by ELISAs. Following co-incubation with UCC118, the amount of TNF.alpha. produced was significantly reduced compared to control cultures. Furthermore, IL-1RA and IFN.gamma. levels dropp...

example 4

[0067] Test for anti-inflammatory bacterial strains

[0068] A number of lactic acid bacteria, which have been isolated from the human gastrointestinal tract, were examined in this novel assay system for anti-inflammatory effect. All bacterial strains were taken from -20.degree. C. glycerol stocks and incubated anaerobically overnight in MRS broth and washed in antibiotic containing medium. Epithelial cell monolayers were grown for 6 weeks prior to the addition of PBMCs and bacterial cells.

[0069] The results of these stimulations can be observed in FIG. 8. Relative to control cultures, two bacterial strains suppressed TNF.alpha. production. The two strains Lactobacillus salivarius strain UCC118, which suppressed production of TNF.alpha., is the subject of WO-A-9835014. The Bifidobacterium longum infantis strain UCC 35624 is the subject of a PCT Application filed concurrently with the present application.

[0070] Inflammation

[0071] Inflammation is the term used to describe the local accum...

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Abstract

Lactobacillus salivarius is useful in the prophylaxis or treatment of undesirable inflammatory activity, especially gastrointestinal inflammatory activity such as inflammatory bowel disease or irritable bowel syndrome. The inflammatory activity may also be due to cancer. The Lactobacillus salivarius is of human origin isolated from resected and washed human gastrointestinal tract. One such strain is UCC 118 described in WO-A-9835014.

Description

[0001] The invention relates to the use of strains of Lactobacillus salivarius.[0002] The defence mechanisms to protect the human gastrointestinal tract from colonisation by intestinal bacteria are highly complex and involve both immunological and non-immunological aspects (V. J. McCracken and H. R. Gaskins, `Probiotics a critical review`, Horizon Scientific Press, UK, 1999, p. 278.). Innate defence mechanisms include the low pH of the stomach, bile salts, peristalsis, mucin layers and anti-microbial compounds such as lysozyme (D. C. Savage, `Microbial Ecology of the Gut`, Academic Press, London, 1997, p.278.). Immunological mechanisms include specialised lymphoid aggregates, underlying M cells, called peyers patches which are distributed throughout the small intestine and colon (M. F. Kagnoff. Gastroenterol. 1993, 105, 1275). Luminal antigens presented at these sites result in stimulation of appropriate T and B cell subsets with establishment of cytokine networks and secretion of a...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A23L1/30A23C9/123A61K9/14A61K9/20A61K9/48A61K39/00A61K45/00A61K47/02A61K47/04A61K47/06A61K47/08A61K47/18A61K47/26A61K47/42A61K47/44A61K47/46A61P1/00A61P1/04A61P1/12A61P19/02A61P29/00A61P31/04A61P31/12A61P35/00A61P37/04A61P37/06A61P43/00C12N1/20C12R1/01C12R1/225
CPCA23C9/1234A23L1/3014A23V2002/00A23Y2220/77A61K39/09A61K2039/52Y10S435/822C12N1/20C12R1/01A61K2039/542Y10S435/853A23V2200/3204A23V2200/324A23L33/135A61P1/00A61P1/04A61P1/12A61P19/02A61P19/04A61P29/00A61P31/04A61P31/12A61P31/14A61P35/00A61P37/00A61P37/02A61P37/04A61P37/06A61P43/00C12R2001/01C12N1/205A23V2400/179
Inventor COLLINS, JOHN KEVINO'SULLIVAN, GERALD CHRISTOPHERO'MAHONY, LIAMSHANAHAN, FERGUS
Owner ENTERPRISE IRELAND
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