Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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Prebiotics and probiotics
Technical Field
This invention relates generally to the use of prebiotic and probiotic
preparations to improve intestinal health and conditions related to microbial
populations in the gastrointestinal tract of host humans and animals, and
thereby improve the health and well being of the host.
Background Art
The concept of probiotics was in use in the early 1900s, however, the
term was only coined in 1965 and has subsequently evolved and numerous
definitions have been proposed. Initially it was used to refer to the
stimulation of the growth of one microbe by another i.e. the opposite of
antibiotic. Today it is generally agreed that a probiotic is a preparation "of
live microorganisms which, applied to human or animal, beneficially affects
the host by improving the properties of the indigenous microbiota". Lactic
acid bacteria and particularly lactobacilli are frequently used as probiotics.
Bifidobacteria are also extensively used as probiotics. Furthermore, microbes
of gastrointestinal origin or strains related to such microbes may also be
used
as probiotics.
The gastrointestinal (indigenous) microbiota contributes significantly
to the health and well being of the host. It is a complex and diverse
population which can reach up to 101' bacteria in an individual and may
have both beneficial and harmful effect; on the host. Some of the beneficial
and harmful effects of the gastrointestinal microbiota are summarised in
Table 1. It is envisaged that these parameters may be influenced by probiodc
administration.
The gut microflora of an healthy subject protects the host from
pathogen invasion, however, in the young, the elderly, and the compromised
patient, this protective barrier is less effective. An individual can be
compromised to various degrees, varying from minor stress related events to
extreme cases such as in immunocompromised patients and patients
undergoing therapy.
The term prebiotic has been coined to refer to carbohydrate
preparations that may be preferentially used to provide a carbohydrate source
for desirable microbes.
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TABLE 1
Influences of the human intestinal microbiota on the host
Beneficial effects Harmful effects
Inhibition of pathogens Constipation
Stimulation of immune system Diarrhoea
Synthesis of vitamins Infections
Aid in digestion Liver damage
Produce metabolic fuel for enterocytesCancer
Maintain stability of ecosystem Flatulence
Metabolise drugs Irritable bowel
Ulcerative colitis
Crohn's disease
Glucans are cell wall polysaccharides with glucose as the main
component sugar having a beta-bonding with mostly beta 1,3 links and also
beta 1,6 links. While originally isolated from black fungi, glucans have since
been found in large quantities in yeast cell walls. Glucans have been shown
to propagate indigenous bifidus bacteria in intestines and have been
proposed to be useful as a pharmaceutical agent for conditioning the
intestine. It has been reported that glucans can function as an
immunostimulator (e.g. Brattgjerd et al 1994) when intraperitoneally
administered.
Probiotic bacteria have been described to exert antimicrobial effects
which refers to the actions of the probiotic preparation on another microbe or
group of microbes. Some probiotic bacteria are directly applicable for
enhancing resistance against intestinal pathogens, prevention of diarrhoea
and constipation (reviewed by Fernandes et al. ; 1987; Katelaris, 1996;
Sanders, 1994). The types of interactions include competitive colonisation as
well as adhesion and growth inhibition.
Competitive colonisation refers to the fact that the probiotic strain
can successfully compete with the pathogen for either nutrients or the site of
colonisation. As many gastrointestinal pathogens attach to the intestinal
mucosa as the first step in infection, it would be beneficial to the host if
this
adhesion could be inhibited . There are reports that lactobacilli produce
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components which inhibit attachment of enterotoxigenic Escherichia coli to
intestinal mucosa (Blomberg et al., 1993), however, there is no evidence as
yet that this occurs in the digestive traca. In addition, various compounds
produced during growth of the probiotiic have beef shown to inhibit
pathogen growth (reviewed by Fernand.es et al., 1987; Klaenhammer, 1988;
Mishra and Lambert, 1996). These include organic acids such as lactic and
acetic acid, reuterin and bacteriocins ('ragg et al., 1976). The organic acids
lower the pH and thereby can indirectly affect growth of the pathogen. In
addition, the lactic and acetic acids produced by these organisms can be
toxic to microbes. Reuterin which inhibits the growth of a very broad range
of cells (Lindgren & Dobrogosz, 1990), i~;s produced by Lactobacillus reuteri
when grown in the presence of glycerol. Numerous bacteriocins have been
reported to be produced by lactobacilli e.g. Acidophilin, Acidolin,
Lactocidin,
Bacteriocin, Bulgarican, Lactolin, Lactobacillin and Lactobrevin (reviewed by
z5 Fernandes et al., 1987; Klaenhalnmer) 1988). Bacteriocins can either have a
very broad range of activity or alternatively specifically inhibit the growth
of
a very limited range of closely related microbes. For example, Lactobacillus
sp exhibited specific antagonistic effects towards Clostridium ramosum
(McCormick & Savage, 1983).
The present inventors have surprisingly found that beta-glucans can be
used to influence pathogen adhesion, alter microbial populations in the
gastrointestinal tract, improve the effecaiveness of probiotic compositions,
and promote growth of a probiotic microorganism. A range of crude and pure
preparations of beta-glucans have been shown to be effective.
Disclosure of the Invention
In a first aspect, the present invention consists in a method of
enhancing a resident population of lacl:ic acid-producing microorganisms in
the gastrointestinal tract of an animal, the method comprising providing to
the animal a beta-glucan derived from cell sacs in combination with other
prebiotics and/or with one or more probiotic microorganisms, such that upon
ingestion, the beta-glucan passes through the gastrointestinal tract
substantially unutilised until the beta-l;lucan and the probiotic
microorganisms reach a site in the gastrointestinal tract where the beta-
glucan is utilised by the resident population of lactic acid-producing
nucroorganisms and the probiotic microorganisms, thereby causing an
increase in number and/or activity of the resident population of lactic acid-
AMENDED SHE
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producing microorganisms and the probiotic microorganisms, wherein the
combination of the beta-glucan and thf: one or more probiotic
microorganisms provides a synergistic effect upon the increase in number
and/or activity of the resident population of lactic acid-producing
microorganisms.
In a second aspect, the present invention consists in a method of
suppressing an undesired population of microorganisms in a total
microorganism population in the gastrointestinal tract of an animal, the
method comprising providing to the animal a beta-glucan derived from cell
sacs in combination with other prebiotics and/or with one or more probiotic
microorganisms, such that upon ingestion, the beta-glucan passes through
the gastrointestinal tract substantially unutilised until the beta-glucan and
the probiotic n>scroorganisms reach a site in the gastrointestinal tract where
the beta-glucan is utilised by a resident population of lactic acid-producing
microorganisms and the probiotic microorganisms thereby causing an
increase in number and/or activity of the resident population of lactic acid-
producing microorganisms and the probiotic microorganisms and
suppressing the growth and/or activity of the undesired population of
microorganisms, wherein the combination of the beta-glucan and the one or
more probiotic microorganisms provides a synergistic effect upon the
increase in number and/or activity of tlhe resident population of lactic acid-
producing microorganisms.
In a preferred form, the undesired population of microorganisms is
enteric pathogens. As will be appreciated, there are a large number of
pathogens including Graln negative bacteria like Salmonella, Escherichia coli,
Campylobacter, Helicobacter, Vibrio, and Pseudomonas; Gram positive
bacteria like Clostridium; viruses like Norwalk virus, Norwalk-like viruses
and Rotavirus; and protozoa like Crytosporidium, Entamoeba, Giardia, and
Dientamoeba. The present invention vvould be suitable for the suppression of
3o many of these pathogens in the gastrointestinal tract of animals.
Suitable beta-glucans include those originating from (a) plants
including cereals such as oats and barley, (b) fungi, (c) yeast, and (d)
bacteria. In addition, nucrobial cell will preparations and whole cells rich
in
beta-glucans are also suitable sources for beta-glucan preparations useful for
the present invention. Monomer residues in glucans can have 1-3 and 1-4, or
1-3 and 1-6 linkages (that is the mononner units are joined through 1.3, 1,4
or
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1,6 bonds) and the percent of each type can vary. Preferably, beta-glucans
derived from yeast, particularly from 5'accharomyces, preferably
Saccharomyces cerevisae, are used for the present invention. It will be
appreciated, however, that other beta-~;lucans would also be suitable. A
5 concentration of up to about 10% when combined with other prebiotics
and/or probiotic nucroorganisms can be used. One percent has been found to
be particularly suitable.
The resident lactic acid-producing microorganism is preferably a
lactobacillus, and more preferably Laci:obacillus fermentum.
1o In a preferred form, the present :invention further includes one or more
oligosaccharides, polysaccharides or other prebiotics. A concentration of
oligosaccharides, polysaccharides or other prebiotics of about 0.001 g to 10 g
per kg body weight per day is preferred.
Preferably, the probiotic microorganism is selected from the group
consisting of lactic acid-producing microorganisms, bifidobacterium, yeast,
and mixtures thereof. Preferably, the lactic acid-producing microorganism is
a lactobacillus, more preferably Lactobacillus fermentum. Preferably, the
yeast is a SaccharomycE~s sp. Typical concentration range of probiotic
microorganisms is 103 to 1013 cells per day.
Although oligosaccharides have been shown to promote bifidobacteria
numbers in animals, prior to the present invention, it was thought that
lactobacillus numbers cannot be changed in a similar manner. Gibson et al
1995 found that oligofructose and inul:in, when fed to humans, selectively
stimulated the growth of bifidobacteria without influencing the numbers of
lactobacillus. From these results and observations by others in the field, it
would not be expected that beta-glucans would positively effect the growth
and/or activity of lactic acid-producing; microorganisms, particularly
lactobacillus, in vivo as found by the present inventors.
It should be further emphasised that the present invention relates to
3o the synergist relationship between the beta-glucans and probiotic
preparations both in terms of proliferation of the probiotics themselves and
inhibition of pathogens. The synergy between beta-glucans and probiotics
preparations results in selective increase in the numbers of specific
beneficial microorganism including probiotic strains in the presence of
glucans. Furthermore, a reduction in numbers of pathogens in the presence
of beta-glucans and additional probiotics is surprisingly significantly
greater
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additive effects of beta glucans or probiotics individually, in reducing
pathogen numbers. This enhancement is not explainable by an increase in
the numbers of some of the probiotics since the synergistic effect is
demonstrable with probiotics which are not enhanced by the inclusion of
glucan".
Throughout this specification, unless the context requires otherwise,
the word "comprise", or variations such as "comprises" or "comprising", will
be understood to imply the inclusion of a stated element or integer or group
of elements or integers but not the exclusion of any other element or integer
or group of elements or integers.
In order that the present invention may be more clearly understood,
preferred forms will be described with reference to the following examples
and drawings.
Brief Description of Drawings
Figure 1 shows the results of Iac;tobacillus in the gastrointestinal tract
of animals fed beta-glucan or control diet; and
Figure 2 shows faecal beta-glucanolytic microorganisms of animals fed
beta-glucan or control diet. Analysis o~f beta-glucanolytic activity on agar
plates containing beta-glucan fTOIIl yeast cell sacs.
Modes for Carrying Out the Invention
EXAMPLE 1
This has been studied by enumerating coliforms, bifidobacterium and
lactobacilli in vitro in the presence of beta-glucan. The beta-glucan used in
this example was prepared from yeast cell sacs. More specifically, aliquots (1
n ll) of human faecal homogenates (10 ~; per 100 ml diluent) were added to
diluted WC broth (diluted 50:50 with (1.05M phosphate buffer) to which were
added the beta-glucan and a lactobacillus or bifidobacterium strain and
various combinations. For each of the combinations, parallel tubes were
prepared with one set being inoculated with Bifidobacterium spp or
Lactobacillus spp. All mixtures were tlhen incubated for up to 24 hours and
bacterial numbers enumerated. Results (Table 2) are expressed as the
numbers of coliforms, total lactobacilli., total bifidobacterium, or total
anaerobes when enumerated as colony forming units. It can be seen that
coliform numbers are unchanged or reduced, while numbers of bifidobacteria
and lactobacilli can be increased up to 10-fold, and selected groups within a
genus can be enhanced.
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TABLE 2
EB'ect of 1% beta-glucan on Lactobacillus and Bifidobacterium
Bacterial
numbers
(CFU/ml
Lactobacillus
Culture mix Coliforms Total Large Bifidobacterium
Colon
Faecal homogenate 3.2 x 10 3.4 x 10 1.2 x < 2
(FH) 10'
FH + 1% glucan 5.2 x 106 5.3 x 105 4.8 x < 2
105
FH + Bifidobacterium
(SUB) NA 1VA NA 1.0 x 106
FH + SUB + 1% glucan NA IVA NA 1.2 x 10'
FH + L. fermentum NA 2.8 x 205 2.8 x NA
(Lf) 105
FH + Lf + 1% glucan NA 1.2 x 106 1.2 x NA
106
NA - not analysed
EXAMPLE 2
This example demonstrates that dietam supplementation with beta-
glucan stimulates gastrointestinal populations of Lactobacillus. In this
study.
animals (8 per group) were provided either bei~a-glucan diet or control diet
(Table 3). The beta-glucan used in this examF~le was prepared from yeast cell
sacs. After 6 weeks feeding. animals were euthanised and luminal content
collected from stomach, ileum, caecum and colon. Collected material was
homogenised and diluted in Wilkens-Charlgren broth (Oxoid). Dilutions
were spread on to Rogosa gear (Oxoid) and incubated anaerobically for 48 h.
Beta-glucan-rich diet resulted in significant increase (P<0.0005) of
Lactobacill us, particularly in the gastric region where an 100 fold increase
was detected (Fig. 1). The increase of lactobacilli numbers in the subsequent
intestinal tract corresponded to about 1.5 log units.
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TABLE 3
Composition of beta-glucan and sucrose diet
Ingredient Amount Amount
(Glucan diet) Control diet
Beta-glucan 450 0
Sucrose 150 600
Casein 200 200
Sunflower 25 25
Canola oil 25 25
Gelatin 20 20
Wheat bran 100 100
Choline chloride 2 2
Methionine 3 3
Standard mineral 35 35
mix
Standard vitamin 10 10
mix
EXAMPLE 3
In addition to studying effects on microbial growth, effects on
adhesion have been investigated. Desirable bacteria such as lactobacillus, as
well as undesirable pathogenic E. coli and Salmonella sp have been grown
either in a standard laboratory broth or in this broth supplemented with beta-
glucans. The beta-glucan used in this example was prepared from yeast cell
sacs. . Bacterial suspensions were incubated with mucosal pieces from
various regions of the gastrointestinal tract. These mucosal pieces were
either used directly or after pre-treatment with the beta-glucan. Results are
shown in Table 4. While adhesion of the pathogen was adversely affected,
the adhesion of the lactobacillus was increased by the presence of the beta-
glucan.
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TABLE 4
Effect of beta-glucans on adhesion
Bacteria adhering
(per mg tissue)
Bacteria
Control tissueTissue + 1% lucanReduction (%)
S. typhimurium 1.69 x 108 5.53 x 10' -- 65
E. coli K88 6.07 x 10' 3.43 x 10' --- 50
L. ermentum 5.37 x 108 6.2 x 108 0
EXAMPLE 4
This example demonstrates that dietary supplementation with beta-
glucan increases resistance to gastrointestinal infection by Clostridium
difficile and S, typllimurium and that this effect is enhanced when glucan-
treated mice were also orally dosed with. Saccharomyces sp cell suspension.
The beta-glucan used in this example w;is acid and alkali washed cell sacs of
yeast. The Saccharomyces sp alone reduced numbers of C. difficile to some
extent and markedly reduced S. typhim urium numbers, Groups of animals (4
groups, 8 animals per group) were provided either beta-glucan diet or control
diet (Table 3). After feeding diets far four weeks, four groups were supplied
drinking water containing cefoxitin (0.0;32 g/L) and D-cycloserine (1.0 g/L)
and subsequently challenged with C. dif~icile (10-8 CFU). Another four
groups were suppled drinking water containing streptomycin (5 g/L) and
neomycin (5 g/L). These animals were subsequently challenged with
S. typhimurium (10-' CFU). After pathogen challenge, animals were
orogastrically dosed with either Saccharnmyces sp (strain FII 542900)(108
CFU in YPG broth), or with fresh YPG broth. Development of infections were
monitored daily by analysis of faecal S. typhimurium or C. difficile. Faecal
material was homogenised and diluted in Wilkins-Charlgen broth (Oxoid).
Dilutions were spread on to either YSA (Oxoid) or C. difficile selective agar
(Oxoid) for analysis of faecal S. typhimuuum and or C. difficile,
respectively.
Animals fed a beta-glucan rich diet were significantly more protected
against colonisation by C. difficile (Table 5), The faecal levels of C.
difficile
were, in animals fed beta-glucan, about 2 log units less than what was
detected in animals fed the control diet, one day post challenge (P<0.05). A
non-significant reduction of S. typhimurium numbers was noted in beta-
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glucan treated mice, while a log 3 reduction in mice dosed with
Saccharomyces sp alone (P<0.05). The combination of beta-glucan diet and
Saccharomyces sp oral administration resulted in a significant reduction
(P<0.05) in faecal numbers of both pathogens when compared to both the
control diet and the Saccharomyces sp dosed mice (Table 5). This reduction
corresponded to 3 and >4 log units for C. difficile and S. typhimurium,
respectively. This corresponded to a marked improvement in weight loss and
other signs of severe infection in animals treated with the combination of
beta-glucan and Saccharomyces sp. In summary, when the beta-glucan is
s0 provided together with probiotic preparations e.g. Saccharomyces, a
surprising synergistic enhancement in the protective effect against pathogens
is noted where greater than log 4 reduction is noted for the combination of
beta-glucan plus probiotics, while the beta-glucan alone or the probiotic
alone reduce pathogen levels by log 1-2. It can be concluded that a beneficial
s5 synergistic effect can be achieved by beta-glucan alone and enhanced by the
combinations of beta-glucan and Sacci'laromyces sp.
TAttLE 5
Reduction of pathogens by oral administration of Saccaromyces sp to beta-
20 glucan fed mice that were chal:(enged with either C. difficile or
S. typh~imurium
Reduction to CFLT
er
faeces
Diet C. di 'cile S. ty himurium
beta-glucan 1.5 * <1
beta-glucan and
Saccharomyces sp 3 * * > 4
Saccharom ces s 0.8 3
* Significantly different from beta-glucan free diet (P<0.05)
25 * * Significantly different from beta-glucan-free diet and Saccharomyces sp
alone.
~MEi'~DED SHEET
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EXAMPLE 5
This example demonstrates that:
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(i) beta-glucanolytic microorganisms a:re present in the gastrointestinal
tract;
(ii) dietary supplementation with beta-glucan stimulates gastrointestinal
populations of beta-glucan degrading microorganisms (includes lactic acid-
producing microorganisms).
In this study, animals (8 per gro,ap) were provided either beta-glucan or
control diet (Table 3). After 4 weeks fE;eding, faecal material was collected,
homogenised and diluted in Wilkins-Charlgen broth (Oxoid). Diluted
material was spread on to beta-glucan agar (Table 6) and incubated
anaerobically for 75 h. Clear zones de~~eloped around colonies formed by
beta-glucanolytic microorganisms.
Relative to animals fed the control diet, density of beta-glucanolytic
population was up to 100 fold greater i.n animals fed beta-glucan diet (Fig.
2).
TAH~LE 6
Comuosidon of beta-~lucan a>;ar
In redient Amount L
Yeast extract 2.5
Trytone 5.0
Peptone 7.5
beta-glucan 10
Cysteine 0.5
NaCI 2.0
KZHPO,~ 2.0
KHZPO,~ 1.0
NaHC03 2.0
MgCl2 0.2
CaClz 0.2
CoCl2 0.02
MnClz 0.02
FeSO~ 0.005
Tween 80 2
Hemin 0.005
Vitamin B1z 0.001
Vitamin K 0.0005
A ar 13.0
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EXAMPLE 6
This example demonstrates that a range of beta-glucans induce the
observed effects. Beta-glucan prepared from a number of Saccharomyces
cerevisae strains and of bacterial origin were used. Both crude forms and
more purified forms were tested, The crude forms were whole cell sacs that
were washed 2-3 times in water and spray dried. The more purified forms
were prepared from the water washed preparations that were subsequently
alkali washed, then acid washed and then water washed prior to spray
drying. When these various beta-glucan forms were incubated with faecal
homogenates diluted in laboratory medium, all forms were degraded (Table
7) and were selectively utilised by lactobacilli when tested using
lactobacillus pure cultures on glucan agar (Table 6).
TABLE 7
Fermentation of beta-glucan preparations by mixed fecal slurries
Beta-
lucan
sam le
1 2 3 4 5
Degradation
(%) 50 >60 >60 >70 >50
Cell sac per
field:
0 hour 156 NA NA clumped NA
72 hours 9.2 NA NA 75 NA
Dry residues
( ) 0.3048 0.2630 0.3097 0.3950 NA
Total
anaerobes 2.9 x 3.1 x 10' 1.4 x 1.9 x 10' NA
10~ 10'
Beta-glucan 1 - water-washed Saccharomyces strain A cell sacs
Beta-glucan 2 - alkali- and acid-washed Saccharomyces strain B cell sacs
(preparation 1)
Beta-glucan 3 - alkali- and acid-washed Saccharomyces str ain B cell sacs
(preparation 2)
Beta-glucan 4 - water-washed Saccharomyces strain B cell sacs
Beta-glucan 5 - bacterial-origin cell sacs
NA - not analysed
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EXAMPLE 7
This example demonstrates that yeast sac beta-glucan is poorly
degraded in the upper regions of the mouse digestive tract and that most of
the degradation occurs in the caecum a.nd colon of the animal where the
microbial population is greatest. Two groups of three SPF Balb/c mice were
fed for 60 hours with a diet containing 40% w/w yeast cell sac beta-glucan.
After the mice were sacrificed, the stomach, duodenum, ileum, jejunum,
caecum and faeces were sampled. Gas1_rointestinal contents were squeezed
from the gut sections and faecal samples were individually homogenised
with 50 mM phosphate buffer and a drop of the homogenate was placed on
microscope slides. The degradation of the beta-glucan from mouse intestinal
tract samples was examined using phase-contrast microscopy. The beta-
glucan granules were degraded by less i_han 20% in the stomach and small
intestine while greater than 70% degradation was noted in the caecum and
faecal homogenates (Table 8).
TABLE 8
Degradation of beta-glucan in mouse intestinal tract
Sam le
source
Stomach Duodenum Ilium Jejunum Caecum Faeces
Degra-
dation < 10% NO < 20% < 20% > 70% > 80%
NO - Not Observed: Few yeast cell sacs were observed in that area, probably
because of the rapid transit time.
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USES
The present invention can be applied to all conditions in which
microbes are identified or proposed as causative agents of disease in both
human and animals and which can be advantageously effected by altering
the numbers and/or activities of beneficial microflora of the gastrointestinal
tr act.
As infective diarrhoea has been shown to be improved by probiotic
dosage, the present invention can be used to enhance the effect of the
probiotic by itself and to reduce the microbial-induced diarrhoea when orally
dosed alone . In addition, the present invention may be used effectively to
improve non-infective diarrhoea which has not been shown to be influenced
by probiotics alone. It could be effective in reducing the effects of dietary
related diarrhoea problems.
Infective diarrhoea refers to all cases of diarrhoea, both acute and
chronic, in which the causative agents can be shown to be microbial,
including bacterial, viral and protozoan. Such infective diarrhoea can
manifest itself in a number of ways e.g. (a) infantile and geriatric
diarrhoea;
(b) antibiotic associated diarrhoea; (c) traveller's diarrhoea; (d) stressed-
induced diarrhoea.
Both prophylactic and therapeutic uses are described in the present
specification. The former can relate to prevention when the individual can
be exposed to potential problems e.g. (i) investigative gastrointestinal
examination when the bowel is decontaminated and can then be recolonised
by an undesirable microbial population; (ii) travellers exposed to an altered
pathogen load or an alteration of the gut ecosystem because of various factors
including diet change, which can predispose the individual to a lower
infective dose of a pathogen. Therapeutic uses relate to the treatment of
established conditions related to an undesirable balance of the gut microflora
or an established pathogen infection.
In summary, glucan preparations singly or together with probiotics
and/or prebiotics such as oligosaccharides can be included in foods or other
preparations for therapeutic or prophylactic use in the follows situations:
i. As a general gut microflora stabiliser
ii. In clinical conditions directly or indirectly related to gastrointestinal
microflora e.g. irritable bowel syndrome (IBS) and inflammatory bowel
disease (IBD), Crohn's disease, diarrhoea and constipation, colon cancer,
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sleep disorders, rheumatoid arthritis, chronic fatigue syndrome,
hyperactivity, and ulcerative colitis
iii. improved intestinal health
iv. directly influence the metabolism of the microbes such that the
5 beneficial activities are enhanced e.g. elevated levels of antimicrobials or
butyrate, and the harmful activities are reduced. e.g. reduced toxin
production
v. directly influence numbers of desirable microbes either directly or
indirectly in the complex mix of gastrointestinal microbes
10 vi. directly influence numbers of undesirable microbes either directly or
indirectly in the gastrointestinal systerr~.
The present inventors have found that beta-glucans and
oligosaccharides are carbohydrates which can be selectively used by
beneficial microbes in the gut which in turn can suppress the numbers of the
15 undesirable microbes.
It will be appreciated by persons skilled in the art that numerous
variations and/or modifications may be made to the invention as shown in
the specific embodiment=s without departing from the spirit or scope of the
invention as broadly described. The present embodiments are, therefore, to
be considered in all respects as illustrative and not restrictive.
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References
Brattgjerd, S, Evensen, O, Lauve, A. (1994). Effect of injected yeast
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Blomberg, L., Henriksson, A. & Conway, P. L. (1993). Inhibition of
Escherichia coli K88 to piglet ilea) mucus by Lactobacillus spp. Applied and
Environmental Microbiology. 59, 34-39.
Fernandes, C. F., Shahani, K. M. & Amer, M. A. (1987). Therapeutic
role of dietary lactobacilli fermented dairy products. FEMS Microbiology
Reviews. 46. 343-356.
Gibson, G. R., Beatty, E.R., Wang, X. & Cummings, J.H. (1995).
Selective stimulation of bifidobacteria in the human colon by oligofructose
and inulin. Gastroenterology 108, 975-982.
Katelaris, P. H. (1996). Probiotic control of diarrhoea) disease. Asia
Pacific Journal of Clinical Nutrition. 5, 39-43.
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