WO2008143527A1 - Probiotic bacterium - Google Patents
Probiotic bacterium Download PDFInfo
- Publication number
- WO2008143527A1 WO2008143527A1 PCT/NZ2008/000110 NZ2008000110W WO2008143527A1 WO 2008143527 A1 WO2008143527 A1 WO 2008143527A1 NZ 2008000110 W NZ2008000110 W NZ 2008000110W WO 2008143527 A1 WO2008143527 A1 WO 2008143527A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- agr
- plantarum
- lactobacillus plantarum
- probiotic
- gastrointestinal
- Prior art date
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
Definitions
- the present invention relates to a probiotic bacterium.
- the present invention broadly relates to an isolated strain of a bacterium which is particularly beneficial to the gastro-intestinal barrier of host animals.
- the gastrointestinal barrier is the tergest interface between man and his external environment. It acts as a "biological bouncer” that protects the host from the entry of bacteria and antigens, and hence, it is critical in maintaining health and wellness.
- the GIB is comprised of physical, 1 ' 2 chemical, 3 immunological 4"6 and microbiologic barriers. 7
- GIB integrity is compromised in conditions such as Inflammatory Bowel Diseases (Crohn's Disease and Ulcerative Colitis) 8 ' 9 , Irritable Bowel Syndrome 10 and some kinds of food-borne - infections 11 ' 12 .
- GIB integrity also deteriorates with aging 13 ' 14 and can be temporarily impaired during times of stress 15 .
- impaired GIB integrity is often associated with acute or chronic inflammation and diarrhoea, such as calf scours, which leads to, at best, impaired growth and reduced productivity.
- probiotics can have a positive effect on gastrointestinal health.
- probiotics There are numerous products on the market that claim to contain probiotic bacteria but few of these are backed up with robust scientific evidence. After extensive searching we found seven probiotic products containing strains of bacteria that had data regarding their efficacy published in international peer-reviewed scientific journals. These published studies are summarised in Table 1.
- VSL#3 which contains eight strains of bacteria - Lactobacillus easel, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus delbruekii subspecies bulgarius, Bifidobacterium Iongum, Bifidobacterium breve, Bifidobacterium infantis, and Streptococcus salva ⁇ us subspecies thermophilus - that is backed up by scientific research.
- the data on the efficacy of the VSL#3 probiotic mixture is summarised in Table 2.
- the inventors devised to ascertain whether they could possibly identify any probiotic bacterial strains that had a greater positive effect on GIB integrity than the commercial probiotic strains identified. To do this, we firstly compared the commercial probiotic strains to determine which had the greatest positive effect, then we used this best commercial probiotic strain as a benchmark to compare numerous potential probiotic strains.
- TEER trans-epithelial electrical resistance
- the diseases, ailments, or disorders of the GIB to which the present invention has application are those associated with deficiencies in the integrity of the GIB.
- the use of probiotic bacteria to assist with gastrointestinal health and the GIB is well known.
- the inventors have however surprisingly discovered that a particular known strain of Lactobacillus plantarum, namely Lactobacillus plantarum AGR 1526 has a significant positive effect on the integrity of the GIB.
- Lactobacillus plantarum AGR 1526 has been shown to positively effect the integrity of the GIB and perform better in this regard than known scientifically proven probiotics tested in this assay, and to exhibit a positive effect for a longer period of time that these well known probiotics, such as Lactobacillus rhamnosus HN 001
- composition to help or improve gastrointestinal health with includes L. plantarum AGR 1526 which is publicly available from DSM under accession number DSM 2648.
- L. plantarum AGR 1526 which is publicly available from DSM under accession number DSM 2648 to manufacture a composition to improve or help maintain gastrointestinal health.
- L plantarum AGR 1526 as publicly available from DSM under accession number DSM 2648 to manufacture a composition to improve or help maintain the integrity of the gastrointestinal barrier.
- a method of preventing, alleviating and/or treating a disease, ailment, or disorder associated with a gastrointestinal disease comprising:
- Lactobacillus plantarum AGR 1526 administering an effective amount of Lactobacillus plantarum AGR 1526 to a person or animal.
- a method of preventing, alleviating and/or treating a disease or ailment associated with a gastrointestinal disease comprising:
- composition which includes an effective amount of Lactobacillus plantarum AGR 1526 to a person or animal.
- Lactobacillus plantarum AGR 1526 as a food or drink additive.
- Lactobacillus plantarum AGR 1526 as an animal feed or drink additive.
- Lactobacillus plantarum AGR 1526 to manufacture a medicament for the prevention, alleviation and/or treatment of a disease, ailment, or disorder associated with the gastrointestinal barrier.
- Lactobacillus plantarum AGR 1526 as a probiotic.
- composition which includes Lactobacillus plantarum AGR 1526 to improve or help maintain the integrity of the gastrointestinal barrier.
- composition which includes an effective amount of Lactobacillus plantarum AGR 1526 to prevent, alleviate and/or treat a disease, ailment, or disorder associated with the gastrointestinal barrier.
- Lactobacillus plantarum AGR 1526 to reduce serum amyloid A levels in a person or animal.
- Lactobacillus plantarum AGR 1526 in the manufacture of a composition to reduce serum amyloid A levels in a person or animal.
- compositions including the present invention will be formulated for oral administration.
- isolated means removed from the natural environment in which the bacteria naturally occurs and is separated from some or all of the coexisting materials in the natural system from which the bacteria has been obtained.
- disorder refers to any abnormality in normal function.
- compositions of the present invention may be formulated in a variety of different ways without departing from the scope of the present invention. In general the type of formulation chosen will be dependent on the end application.
- the "effective amount" of Lactobacillus plantarum AGR 1526 to be delivered may vary, but can be easily determined by those skilled in the art, via routine trial and experimentation and/or by reference to existing probiotic products or literature thereon.
- the present invention may preferably include formulations suitable for direct application to grass or animal feed e.g. spray form.
- L. plantarum AGR 1526 as a probiotic bacterium provides an enhanced effect on GIB integrity over known probiotics, as well as providing the public with a useful choice.
- FIG. 1 Schematic diagram of the Endohm12 used to measure the resistance across the epithelial cell monolayer
- FIG. 4 Images of pulse-field gel electrophoresis of L plantarum strains.
- Figure 5 16s rRNA sequence of AGR 1526
- Figure 6 Images of pulse-field gel electrophoresis of AGR 1526 compared to commercial L. plantarum strains.
- TEER trans-epithelial electric resistance
- Lactobacillus plantarum had a positive effect on GIB integrity so we choose to test numerous strains of L. plantarum to determine if all strains of this species had a similar effect or if the effects were strain specific.
- the strains of L. plantarum were obtained from the German culture collection Deutsche Sammlung von Mikroorganismen (DSM).
- Agarose blocks were removed from the moulds and the cells were lysed by incubating the agarose blocks for 18 hours at 37° C in EC buffer (1 M NaCI, 6 mM Tris.CI, 100 mM EDTA, 1% (w/v) sarkosyl, pH 7.6) containing 5 mg ml '1 lysozyme.
- the agarose blocks were then incubated with proteinase K (1 mg ml "1 in 0.5 M EDTA, 1% sarkosyl, pH 8.0) for 24 hours at 37° C, and with 1 mM phenylmethylsulfonyl fluoride (PMSF) in TE 10/1 (10 mM Tris.CI, 1 mM EDTA, pH 8.0) for 2 hours at 37° C.
- PMSF phenylmethylsulfonyl fluoride
- Slices (1-2 mm) were cut from the agarose blocks with a sterile coverslip, and washed twice with gentle shaking in TE 10/0.1 (10 mM Tris.CI, 0.1 mM EDTA, pH 8.0) at room temperature. Slices were , transferred to microcentrifuge tubes, washed once at 4° C with restriction enzyme buffer, and incubated for 16-18 hours with the appropriate restriction enzyme in a total volume of 100 ⁇ l.
- the enzymes used to differentiate strains of L plantarum were Asc ⁇ and I-Ceul (New England Biolabs, Beverly, MA).
- the slices were washed once with TE 10/1 for one hour at 4° C and loaded into the wells of a 1% agarose gel (Bio-Rad pulsed field certified agarose prepared in 0.5X Tris-borate buffer).
- the wells were sealed with agarose and the gel run in 0.5X Tris-borate buffer using a CHEF DR III pulsed-field gel electrophoresis apparatus and model 1000 mini chiller (Bio-Rad). Gels were run at 200V for 20 hours at 14° C, and with the pulse time ramped from 1 to 30 seconds for Asc ⁇ digests, and from 10 to 100 seconds for I-Ceul digests.
- Multimers of bacteriophage lambda prepared for use as pulsed-field gel molecular size standards were used to give an indication of fragment sizes.
- Gels were stained with Gelstar nucleic acid gel stain (Cambrex Bio Science, Rockland, ME), destained with water, and photographed using a Kodak Gel Logic 200 Imaging System (Eastman Kodak, Rochester, NY).
- the bacterial strains were identified based on their 16s rRNA sequences. From the isolated genomic DNA the 16s rRNA was amplified using with FD1 (5'- AGAGTTTGATCCTGGCTCAG-S 1 ) and RD1 (5'-AAGGAGGTGATCCAGCC-S') primers and PCR supermix (Invitrogen, Auckland) using a Thermo Hybaid PX2 thermocycler (Thermo Electron Corporation) and purified using a QIAquick PCR purification kit (QIAGEN). The florescent labelled DNA was prepared using PCR with Big Dye Terminator v3.1 Cycle Sequencing kit (Applied Biosystems) and purified using ethanol/EDTA precipitation.
- the DNA sequencing was carried out by the Allan Wilson Centre Genome Service at Massey University, Palmerston North, New Zealand.
- the DNA sequence contigs were aligned using the ContigExpress Vector NTI software (Invitrogen).
- the determined sequences were compared to known bacterial sequences using the NCBI Blast database.
- FIGS 1 and 2 illustrate the assay setup.
- the TEER is a function of the strength of the tight junctions between the epithelial cells of the monolayer. When the tight junctions are well formed it is more difficult for the current to pass through the monolayer of cells so the TEER increases. Conversely, when the tight junctions are compromised the current can pass more easily through the monolayer so the TEER decreases.
- Caco-2 cells (a human intestinal epithelial adenocarcinoma cell line) were grown on semi-permeable membranes for 5 days until they reached confluence and formed tight junctions between adjacent cells.
- the Caco-2 cells were grown in M199 with 10% foetal bovine serum, 1% non-essential amino acids and 1% penicillin- streptomycin solution at 37° C in 5% CO 2 .
- the monolayers were prepared the day before the TEER assay by removing the medium, washing three times with phosphate buffered saline and adding M199 with 1% non-essential amino acids, without foetal bovine serum and penicillin-streptomycin to ensure growth of the bacterial strains.
- the bacterial strains were grown overnight in MRS broth at 37 0 C in 5% CO 2 (except the E. coli K12 negative control which was grown in LB broth aerobically).
- the bacterial cells were collected by centrifugation and suspended in tissue culture media (M199 with 1% non-essential amino acids) to the required optical density at 600 nm. At this wavelength the turbidity of the solution is proportional to the bacterial cell concentration.
- the bacterial solutions were added to the top to the monolayer of Caco-2 and the TEER was measured every 2 hours for 12 hours. For each experiment three bacterial strains were tested and the following controls were included; tissue culture media without bacteria added, positive bacterial strain (L. plantarum VSL#3 for commercial strain testing and the best commercial strain for the experimental strain testing) and negative bacterial strain (E. coli K12). Each bacterial strain was tested in quadruplicate.
- each insert was lifted into an electrode chamber with electrodes at the top and bottom (ENDOHM-12 tissue culture chamber, World Precision Instruments, Florida, USA) using sterile tweezers and the resistance was measured using a voltohmmeter (EVOM Epithelial Tissue Voltohmmeter, World Precision Instruments, Florida, USA).
- ENDOHM-12 tissue culture chamber World Precision Instruments, Florida, USA
- sterile tweezers were used to measure the resistance across the monolayers and the resistance was measured using a voltohmmeter (EVOM Epithelial Tissue Voltohmmeter, World Precision Instruments, Florida, USA).
- a schematic diagram of the EndOhm chamber is given in Figure 3. The resistance was measured every 2 hours for 12 hours.
- change in TEER TEER ( ⁇ cm 2 ) / initial TEER ( ⁇ .cm 2 ) - 100 (%).
- the mean change in TEER was plotted against time, with the error bars showing the standard error of the mean.
- a Student's t-Test was used to compare treatments. Statistical differences between treatments were declared at a probability less than 0.05 whilst a probability below 0.1 but above 0.05 was considered to represent a trend.
- Pulse field gel electrophoresis was used to compare the L. plantarum strains to confirm that they were all different.
- Figure 4 shows the resulting images.
- AGR 1526 has a unique profile compared to the other L. plantarum strains that were tested.
- AGR 1526 16s rRNA sequencing was used.
- the 16s rRNA sequence is given in Figure 5. This was compared to other known sequences in the NCBI Blast database and it confirmed that AGR 1526 is a strain of Lactobacillus plantarum (99% match).
- the pulse-field gel electrophoresis profile of AGR 1526 in Figure 6 shows this strain is different to the three commercial L plantarum strains tested.
- Table 3 Summary of the results of the in vitro assays testing the effect of commercial probiotic strains on trans-epithelial electrical resistance (TEER).
- the three best performing commercial probiotic strains in the TEER assays were L plantarum 299, L rhamnosus HN001 and B. lactis Bb12. All three strains had a positive TEER effect (compared to control media); however, only L rhamnosus HN001 produced a statistically greater TEER va
- AGR 1526 The effect of AGR 1526 on TEER compared to L. rhamnosus HN001 and control media (no bacteria) is illustrated in Figure 8.
- AGR 1526 caused a larger average increase in TEER than L rhamnosus HN001 but this was only significantly different (P ⁇ 0.05) at 2 hours.
- the probiotic bacterium AGR 1526 (a strain of L. plantarum) performed better than the best commercial probiotic strain L. rhamnosus HN001 in the TEER assay.
- mice will be used as a model for human Inflammatory Bowel Diseases.
- the effect of AGR 1526 on key performance indices including growth rate, general health score, gut histology, immune profile and bacteria composition will be monitored.
- IL10 " ' " mice were used as a surrogate model. When raised in conventional conditions these mice spontaneously develop chronic colonic inflammation with symptoms similar to those observed in human patients with Inflammatory Bowel Diseases (IBD).
- IBD Inflammatory Bowel Diseases
- mice were randomly assigned to the following treatments according to a complete block design (15 IL10 " ' " mice (C57BL/6J background) and 8 C57BL/6J (C57) mice per group):
- mice were orally dosed daily via pipette with the probiotic bacterial strain (approximately 10 9 colony forming units (CFU)) prepared in the vehicle fluid (20% glucose in skim milk).
- CFU colony forming units
- the mice were inoculated with endogenous intestinal bacteria Enterococcus species (EF) (10 6 CFU) and complex intestinal flora (100 ml) by oral gavage to ensure consistent and more rapid development of intestinal inflammation in IL10 ⁇ mice (Roy et al. 2007).
- EF endogenous intestinal bacteria Enterococcus species
- complex intestinal flora 100 ml
- mice A commercial mouse diet (AIN-76A) was offered and food consumption was recorded daily. All mice were weighed and a faecal sample collected thrice weekly. Each day, mice were checked for the presence of loose stools or blood in faeces (an indication of intestinal inflammation) and the General Health Score (GHS; commonly used criteria for rating mouse wellness in a range from 1 (very ill) to 5 (healthy)) was established. At 12 weeks of age the mice were euthanized by CO 2 asphyxiation and cervical dislocation. Blood and tissue samples will be immediately collected post-mortem and rapidly frozen in liquid nitrogen or fixed in formalin and stored at room temperature until analysis.
- GHS General Health Score
- Inflammation was determined by analysis of serum amyloid A levels in plasma using a murine specific Tridelta PhaseTM range serum amyloid A kit and an Enzyme Linked lmmuno Sorbent Assay (ELISA) according to manufacturer (Tridelta Development Limited, Maynooth, . County Kildare, Ireland).
- ELISA Enzyme Linked lmmuno Sorbent Assay
- a volume of 50 ⁇ L of anti-serum amyloid A/streptavidin-horse radish peroxidase conjugate and 50 ⁇ L of diluted plasma sample or standard were added to each well that is coated with a monoclonal antibody specific for serum amyloid A. After 1 hour incubation (37°C) the plates were washed four times with 400 ⁇ L diluted wash buffer to remove all of the unbound material.
- the histological analysis of colon samples was carried out at Gribbles Veterinary Pathology in Hamilton.
- the colon tissue samples were fixed in formalin and embedded in paraffin.
- the embedded tissue samples were sliced to obtain 5 ⁇ m thick sections which were stained with haematoxylin and eosin for light microscopy examination.
- the stained sections were assessed for inflammation based on a combination of inflammatory cell infiltration (monocytes, neutrophils, eosinophils, plasmocytes, fibrin exudation and lymphangiectasis), tissue destruction (enterocyte loss, ballooning and degeneration, oedema and mucosal atrophy) and tissue repair (hyperplasia, angiogenesis, granuloma and fibrosis).
- a rating score of between 0 (no change from normal tissue) and 3 (lesions involved in most areas and all layers of the intestinal section including mucosa, muscle and omental fat) was applied to each colonic section for each aspect of inflammation (e.g. monocytes, oedema, hyperplasia etc).
- the sum of the score for inflammatory cell infiltration, tissue destruction and tissue repair was used to represent the total histological injury score for each colonic section.
- the sum of the inflammatory cell infiltration was multiplied by 2 to give more weight to this value, as this represented the main characteristic of the observed inflammation.
- the mean daily feed intakes for each treatment group for the whole experimental period are summarised in Table 1. There were no significant differences in mean daily feed intakes between mouse strains or between AGR strain-inoculated mice treatment groups over the experimental period. Additionally, there were no mouse strain effects, AGR strain treatment effects or interaction on feed intake at most times.
- the general health score was not affected by the mouse strain or the inoculation with AGR strains which means there were no noticeable indications of physical deterioration (e.g. loose stools, blood in stools, loss of hair etc).
- the histology injury score was greater in IL10 " ' " control mice (inoculated with vehicle only) compared to C57 control mice or C57 mice inoculated with the AGR strains (Table 3).
- the plasma concentration of serum amyloid A was higher in IL10 " ' " mice inoculated with the AGR strains or the vehicle only (191 ⁇ g/ml) compared to the C57 mice (as expected, not detectable).
- Serum amyloid A ( ⁇ g/ml)
- mice were significantly different for all treatments (P ⁇ 0.05).
- ND not detectable (as expected).
- the bioassays chosen for this milestone were a cell adherence assay and an immune challenge assay.
- the cell adherence assay tested the ability of the bacterial strains to adhere to intestinal cells. This property is important because it is a crucial and a prerequisite step for colonisation of the intestinal tract.
- the bacterial cultures (L. rhamnosus HN001 , AGR1526) were grown overnight in 4OmL of MRS broth at 37°C with 5% CO2. The cultures were mixed and then aliquoted into lots of 1OmL in sterile tubes. The tubes were centrifuged (20 minutes at maximum speed) to collect the bacterial cell pellets and the supernatant was removed. The pellets were resuspend to an approximate cell concentration of 10 8 CFU/mL in the following test solutions:
- the number of viable bacterial cells was determined after 2 and 4 hours in triplicate using standard enumeration techniques. These time points were chosen to represent the amount of time it would take the bacterial strains to pass through the upper gastrointestinal system to the intestinal tract. The concentrations of pepsin and bile and the pH values were chosen to represent the range of these variables (high and low concentrations) found in the human gastrointestinal system.
- HEp-2 epithelial larynx cell line commonly used in adherence assays because they rapidly grow to confluence (complete layer of cells; 48 hours).
- Caco-2 cells are a human colon epithelial cell line that better represents the intestinal barrier but take longer to grow (5 to 7 days to grow to confluence and 15 to 20 days to differentiate).
- the epithelial cells were grown in the presence of foetal calf serum and antibiotics in 24-well tissue culture plates at 37°C with 5% CO 2 .
- the antibiotics were removed from the epithelial cells by washing with pre-warmed phosphate buffered saline (PBS) to allow the survival and growth of the test bacterial strains, and the cells were bathed in either DMEM with 1% non-essential amino acids for HEp-2 cells or M199 with 1% non-essential for Caco-2 cells.
- Bacterial strains to be assessed were grown overnight in MRS broth and approximately 10 7 (10 ⁇ l) were added to each well with each strain being assessed in triplicate. After 3 hours incubation at 37°C (5% CO 2 ) bacteria were removed from one 24-well tissue culture plate and the epithelial cells were washed gently (x5) with pre-warmed PBS.
- Bacterial separation from epithelial cells was mediated by adding 1ml of a 1% solution of Triton X-100 to each well and stirring for 10 minutes. Bacteria were quantified by using standard enumeration techniques. To assess adherence over 6 hours, non-adherent bacteria were removed after 3 hours and the epithelial cells were washed gently (x5) with PBS as described previously. Fresh media was then added to each well and the tissue culture plate incubated for a further 3 hours prior to enumeration.
- the ability of the bacterial strains to adhere to epithelial cells was determined using undifferentiated and differentiated Caco-2 cells ( Figure 4) and HEp-2 cells ( Figure 5).
- AGR1526 was the better strain at adhering (higher number of viable cells attached) and remained attached (lower drop in viable cells attached between 3 and 6 hours) to the epithelial cells.
- AGR1526, and L rhamnosus HN001 adhered to the epithelial cells to a similar extent.
- the HEp-2 model is often used due to its ease of growth, the Caco-2 model is more reliable as it is a human colon epithelial cell line.
- AGR1526 was the best at tolerating the conditions that mimicked the gastrointestinal tract and at adhering and remaining attached to intestinal epithelial cells.
- the calves were allocated to a treatment group which received a composition including AGR1526 in phosphate buffered saline (PBS, pH7.3).
- the untreated control group received the diluent solution (phosphate buffered saline, as placebo).
- the animals were weaned off calf milk replacer with concurrent removal of the treatments, from day 42 to day 48 of the trial.
- the plasma concentration of serum amyloid A was measured using an ELISA assay substantially the same as that used in the mouse trial described above.
- the plasma concentration of serum amyloid A measured in the treatment and control groups are shown in Figure 14. As can be seen, the serum amyloid A concentrations in the calves treated with the AGR1526 containing composition were lower (P ⁇ 0.05) than that of the control group.
- AGR 1526 Potential uses for AGR 1526 include, but are not limited to:
- GIB integrity during illness e.g. Inflammatory Bowel Diseases, Irritable Bowel Syndrome
- infection e.g. food poisoning
- ⁇ Inclusion in feed or as a feed additive for livestock e.g. cattle, pigs, sheep
- livestock e.g. cattle, pigs, sheep
- Lactobacillus casei strain GG reverses increased intestinal permeability induced by cow milk in suckling rats. Gastroenterology 105:1643-1650.
- VSL#3 probiotic bacteria
Abstract
Description
Claims
Priority Applications (1)
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AU2008253830A AU2008253830B2 (en) | 2007-05-18 | 2008-05-16 | Probiotic bacterium |
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NZ555259 | 2007-05-18 | ||
NZ555259A NZ555259A (en) | 2007-05-18 | 2007-05-18 | Use of L. plantarum DSM 2648 to treat gastrointestinal barrier conditions |
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WO2008143527A1 true WO2008143527A1 (en) | 2008-11-27 |
WO2008143527A8 WO2008143527A8 (en) | 2009-07-23 |
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PCT/NZ2008/000110 WO2008143527A1 (en) | 2007-05-18 | 2008-05-16 | Probiotic bacterium |
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AU (1) | AU2008253830B2 (en) |
NZ (2) | NZ555259A (en) |
WO (1) | WO2008143527A1 (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0131114A2 (en) * | 1983-07-08 | 1985-01-16 | Hüls Aktiengesellschaft | Process for the preparation of a dry storage-stable bacteria preparation |
WO2007003917A1 (en) * | 2005-07-01 | 2007-01-11 | Matforsk As | Probiotic lactobacillus plantarum or pentosus starter strains |
-
2007
- 2007-05-18 NZ NZ555259A patent/NZ555259A/en unknown
-
2008
- 2008-05-16 NZ NZ588500A patent/NZ588500A/en unknown
- 2008-05-16 AU AU2008253830A patent/AU2008253830B2/en active Active
- 2008-05-16 WO PCT/NZ2008/000110 patent/WO2008143527A1/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0131114A2 (en) * | 1983-07-08 | 1985-01-16 | Hüls Aktiengesellschaft | Process for the preparation of a dry storage-stable bacteria preparation |
WO2007003917A1 (en) * | 2005-07-01 | 2007-01-11 | Matforsk As | Probiotic lactobacillus plantarum or pentosus starter strains |
Non-Patent Citations (4)
Title |
---|
BRINGEL F. AND HUBERT J.-C.: "Extent of Genetic Lesions of the Arginine and Pyrimidine Biosynthetic Pathways in Lactobacillus plantarum L. paraplantarum L. pentosus, and L. casei: prevelence of CO2-Dependent Auxotrophs and Characterization of Deficient arg Genes in L. plantarum", APPL. ENVIRON. MICROBIOL., vol. 69, no. 5, 2003, pages 2674 - 2683 * |
CURK M.C. ET AL.: "Caracterisation Biochimique des Lactobacilles brassicoles", LAIT, vol. 73, 1993, pages 215 - 231 * |
MOLIN G.: "Probiotics in Food not Containing Milk or Milk Constituents, with Special Reference to Lactobacillus plantarum 299v", AM. J. CLIN. NUTR., vol. 73, no. SUPPL., 2001, pages 380S - 385S, XP000984969 * |
PAVAN S. ET AL.: "Use of Mouse Model to Evaluate the Persistence, Safety, and Immune Modulation Capacities of Lactic Acid Bacteria", CLIN. DIAGN. LAB. IMMUNOL., vol. 10, no. 4, 2003, pages 696 - 701 * |
Also Published As
Publication number | Publication date |
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NZ555259A (en) | 2010-11-26 |
WO2008143527A8 (en) | 2009-07-23 |
AU2008253830A1 (en) | 2008-11-27 |
NZ588500A (en) | 2011-09-30 |
AU2008253830B2 (en) | 2013-02-07 |
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