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Probiotics have been used for many years to aid
in restoring and maintaining a healthy intestinal balance in favor of
healthful bacteria, which is essential in maintaining good health. Probiotics
are organisms or supportive substances that improve intestinal microbial
balance, and include lactobacillus acidophilus (L. acidophilus), bifidobacteria
and bioactive proteins such as immunoglobulin A (igA) and lactoferrin.
A major consideration in the choice of probiotics is to choose a strain
that can survive and establish itself under the conditions encountered
in the intestinal environment. Therefore, when choosing a probiotic supplement
it is necessary to consider those qualities and characteristics essential
to establishment and activity of L. acidophilus in the intestinal environment,
such as bile resistance and intestinal adherence. The L. acidophilus NCFM
strain has been thoroughly researched and is recognized for its ability
to survive in the presence of bile or stomach acid and adhere to the intestinal
mucosa. In addition, studies have demonstrated many beneficial effects
of the L. acidophilus NCFM strain, such as cholesterol assimilation and
reduction of pro-carcinogenic fecal bacterial enzyme activity.
Learn more
The use of probiotics to promote intestinal
balance
The NCFM strain of lactobacillus acidophilus
(L. acidophilus)
Intestinal adherence
Bile tolerance
Bacteriocin production
Assimilation of cholesterol
Fecal enzyme activity and antimutagenicity
Small bowel bacterial overgrowth
Viability assays
Bioactive proteins
References
The use of probiotics to promote intestinal balance
The human
intestinal microflora is complex, with total counts of about 1,000 bacteria
per gram of stool. Among this vast number of organisms
are at least 500 species of anaerobes and many facultative organisms,
within which are several species of lactobacilli and bifidobacteria.
This intestinal microflora is a highly active society of organisms,
possessing a diverse complex of enzymes that perform extremely varied
functions, both beneficial and detrimental. The delicate, yet critical,
balance maintained among this enormous bacterial population plays an
important role in maintaining not only intestinal health, but the overall
health of the patient.
Probiotics are viable organisms and supportive
substances that improve intestinal microbial balance, such as lactobacillus
acidophilus (L. acidophilus) and bioactive proteins.
The empirical evidence that, for many years, linked the use of fermented
dairy products such as yogurt and milk with the promotion of intestinal
health is today well supported by modern science. The ability of the probiotic
L. acidophilus to help prevent pathogenic bacteria from proliferating
and healthy bacteria from becoming toxic is well documented.
When the proper strain is chosen, it may help to maintain a population
equilibrium, or balance, between the different forms of microorganisms,
curtailing their potential overgrowth and pathogenicity.
and characteristics essential to establishment and activity of L. acidophilus
in the intestinal environment, such as bile resistance and intestinal
adherence. The L. acidophilus NCFM strain has been thoroughly researched
and is recognized for its ability to survive in the presence of bile or
stomach acid and adhere to the intestinal mucosa. In addition, studies
have demonstrated many beneficial effects of the L. acidophilus NCFM strain,
such as cholesterol assimilation and reduction of pro-carcinogenic fecal
bacterial enzyme activity.
Bifidobacteria
is another probiotic naturally occurring in the human intestine, with
bifidobacterium infantis being the first flora to colonize the intestines
of newborns. Research studies have documented several beneficial effects
of bifidobacteria when given to infants, such as its effectiveness against
a specific strain of enteropathogenic escherichia coli,
in prevention of enteric infections, and in decreasing
the growth of candida albicans.
What is
it that enables L. acidophilus and bifidobacteria to help maintain the
proper balance between the different forms of microorganisms in the
intestine? They produce organic acids that reduce intestinal pH and
thereby inhibit the growth of acid-sensitive bacteria, including many
pathogenic species. Lactobacilli, which are frequently more acid tolerant
than other organisms, produce lactic acid, hydrogen peroxide, and possibly
acetic and benzoic acids. Acids produced by bifidobacteria
include short-chain fatty acids (SCFAs) such as acetic, propionic and
butyric acids, as well as lactic and formic acids.
At optimal pH values they exert several inhibitory influences on bacterial
cell growth. The most plentiful SCFA produced by bifidobacteria
is acetic acid, which exerts a wide range of antimicrobial activity
against yeasts and molds as well as bacteria.
In addition
to lactic and other acids, lactobacilli have the capacity to secrete
numerous metabolites, or endotoxins, that kill pathogenic bacteria.
A variety of antibacterial/anti-yeast substances have been isolated
such as lactocidin, lactobicillin, lactobreven and acidolin.
Because these substances are difficult to isolate and stabilize, their
value can best be obtained through the administration of those strains
known to secrete these agents as a part of their life cycle.
The NCFM strain of lactobacillus acidophilus
A great
deal has been learned in the last few decades through intense study
on many different strains of L. acidophilus, bifidobacteria and other
forms of healthful microorganisms. Because probiotic strains vary greatly,
their impact hinges upon the specificity of the strains that are used
and the method of culturing, packaging and handling of the product.
The L. acidophilus NCFM strain, developed at North Carolina State University,
is perhaps the most extensively researched L. acidophilus strain available.
A multitude of research studies conducted at leading universities have
been published documenting the many beneficial properties of the NCFM
strain.
A
number of factors should be considered when selecting a culture of L.
acidophilus. Because cultures exhibit host specificity, it is desirable
to select an organism originating from the human intestinal tract.
The NCFM strain is one that has been isolated from the human fecal flora.
In addition, DNA studies have revealed great genetic variability within
strains that are designated as L. acidophilus. Out of several
groups of the organism, researchers determined that only strains from
the A1 homology group, which includes the NCFM strain, should be classified
as true L. acidophilus.
Additional
factors that are important in selecting a strain that is able to function
by surviving and growing in the intestinal tract include bile tolerance,
bacteriocin production and ability to adhere to the intestinal wall.
The NCFM strain has been shown to not only meet the strict criteria
of purity and viability, but also to survive and implant in the gut
and produce beneficial effects.
Intestinal adherence
The primary
objective of supplying L. acidophilus is to establish the bacterium
in the intestinal tract. The stomach and intestinal tract represent
a hostile environment that can easily discourage growth or survival
of microorganisms. Although many lactobacilli survive selective pressures
of this environment, flow rates of digesta through the small intestine
would wash out any organism unable either to multiply rapidly enough
to avoid dilution or to maintain their residence by physical attachment
to the intestinal epithelium.
According to one researcher, many lactobacilli products do not appear
to live up to claims regarding human gastrointestinal adherence.
Only a limited number of strains have actually been shown in vitro to
adhere, including the NCFM strain. The ability of the NCFM strain to adhere
to the intestinal wall has been demonstrated in several in vitro studies
utilizing human intestinal cells.An in vivo study has
shown that the NCFM strain, when consumed in milk, is capable of surviving
and implanting in the intestinal tract of humans. The researchers
determined this by analyzing the fecal flora of healthy males after consuming
non-fermented milk containing the NCFM strain of L. acidophilus. Highly
significant increases in bile-resistant facultative lactobacilli were
seen in the group consuming L. acidophilus, indicating successful implantation.
These numbers decreased after the milk feeding was stopped, although most
subjects retained considerably higher counts than they had before feedings.
Bile tolerance
Bile tolerance
is considered to be an important characteristic of L. acidophilus that
enables it to survive, grow and exert its action in the small intestine.
Strains that are able to grow and metabolize in the presence of physiological
levels of bile should logically be more likely to survive intestinal
transit. Although the degree of bile tolerance required
for maximum growth of the organism in the intestinal tract is not known,
it is important to select one having a high degree of bile resistance.
There is a wide range in the ability of cultures to grow in the presence
of bile. Studies have shown that the NCFM strain is capable
of growing in bile concentrations of up to 3%
and an in vivo study demonstrated that the NCFM strain survives in the
presence of human gastric juice.
Bacteriocin production
Suppression
of undesirable intestinal bacteria through antimicrobial action continues
to be a major benefit attributed to L. acidophilus. This intestinal antagonism
is dependent on intrinsic properties of the lactobacilli that enable them
to compete for, and maintain, their residence in the intestinal environment.
Therefore, the ability to produce effective antimicrobial substances becomes
an important consideration when selecting strains. Broad-spectrum
inhibition has been clearly demonstrated for organic acids and hydrogen
peroxide produced by L. acidophilus, including the NCFM strain.
Bactericidal
proteins with a more specific spectrum of antagonistic activity, termed
bacteriocins, are produced by some strains of L. acidophilus. The bacteriocins
of Lactobacillus species usually prove inhibitory to bacteria that are
closely related to the producer strain or that compete for the same ecological
niche. It is important to select a culture of L.
acidophilus that will be able to compete and grow well in the presence
of similar bacteria. Some studies have shown the NCFM strain
exhibits significant bacteriocin activity against closely related Lactobacillus
species, which provides it with an advantage in being able to establish
and grow in the intestinal tract. Researchers have
even isolated and studied a specific bacteriocin produced by the NCFM
strain, called lactacin B, which is active against closely related lactobacilli
such as L. bulgaricus and L. helveticus.
Because
many bacteriocins have been identified for lactobacilli, the practice
of mixing L. acidophilus products together with other species groups (i.e.,
L. bulgaricus, L. leichmannii) may hinder therapeutic efforts due to significant
bacteriogenic activity by these species groupings.
By combining various strains together, as in a broad-spectrum probiotic,
the beneficial strains may be rendered innocuous.
Assimilation of cholesterol
Several
studies have reported that ingestion of L. acidophilus can result in decreased
serum cholesterol levels in humans and animals. Certain
strains of L. acidophilus have the ability in vitro to assimilate cholesterol,
as shown by the appearance of cholesterol in the cells during growth and
decreases in the concentrations of cholesterol in the growth medium.This uptake of cholesterol occurred only when the culture was growing
anaerobically in the presence of bile. These conditions required in the
in vitro system for cholesterol uptake by L. acidophilus would also be
expected to occur in the human intestinal tract. Such assimilation of
cholesterol in the small intestine may be important in reducing the absorption
of dietary cholesterol from the digestive system into the blood.
If the
purpose in using the dietary culture is to provide a beneficial influence
on serum cholesterol levels, the culture should very actively assimilate
cholesterol during growth under conditions existing in the intestinal
tract. Data from one study showed wide variation in the
ability to assimilate cholesterol among L. acidophilus cultures of human
origin. Among 13 isolates of L. acidophilus, the NCFM
strain ranked first in cholesterol assimilation over 16 hours of growth.
Fecal enzyme activity and antimutagenicity
There
is considerable interest in the metabolic activities of the intestinal
microflora, especially in relation to the etiology of colon cancer.
Epidemiological studies indicate a correlation between regular consumption
of fermented dairy products and low incidence of colon cancer.
To investigate this, several studies have involved measurements of fecal
bacterial enzymes, such as
B-glucuronidase, nitroreductase and azoreductase,
which are known to catalyze reactions that convert procarcinogens to
carcinogens. In one study, oral administration of
L. acidophilus NCFM to meat-fed rats substantially reduced the activities
of these fecal bacterial enzymes. Similarly, in a study
with seven human subjects, it was found that supplementing the diet
with L. acidophilus NCFM for one month significantly reduced fecal
B-glucuronidase
and nitroreductase activities. In a larger study with
21 human subjects, reductions of two- to four-fold in the activities
of the three fecal enzymes were observed during a four-week period of
L. acidophilus NCFM supplementation. Whether these changes
in bacterial enzyme activity directly affect colon cancer risk is a
matter of speculation.
To investigate the role of L. acidophilus NCFM
in prevention of chemically induced colon tumors in rats, two groups of
rats were challenged with a colon cancer inducing agent.
The experimental group, which was fed a supplement of the L. acidophilus
NCFM strain, showed a lower incidence of colon cancer after a 20-week
induction period than the control group. This difference was not observed
after 36 weeks, indicating that L. acidophilus may play a role in delaying
the initiation of colon cancer.
Small bowel bacterial overgrowth
Small
bowel bacterial overgrowth (SBBO), well known to occur in end-stage kidney
failure, is responsible for producing toxic amines such as dimethylamine
(DMA).These toxic amines cause general chronic renal failure
symptoms as well as target organ dysfunction, especially in the brain.
In a recent study, L. acidophilus NCFM was administered to hemodialysis
patients to determine if supplementation could modify SBBO, thereby reducing
the toxic levels of amines in the blood. The patients treated
with NCFM for at least one month showed significant reductions in serum
DMA levels as well as levels of nitrosodimethylamine, a potent carcinogen.
The researchers concluded that L. acidophilus NCFM changed small bowel
pathobiology by modifying metabolic actions of SBBO, reducing generation
of toxins and carcinogens with no adverse side effects.
Viability assays
For L.
acidophilus to establish and react within the intestinal environment,
the bacteria must be in a viable condition. The viability of the selected
strain can be determined through third-party laboratory analysis of
the number of colony forming units (cfu) per unit weight (grams) and
bile resistance (oxgall bile test) for each batch produced. The laboratory
assay results should be provided by the culture supplier, expressed
as the ratio of bile resistant cfu per gram to total cfu per gram. A
high ratio, above 90%, indicates high viability of the organism in the
gastrointestinal tract. The importance of this analysis
cannot be understated, as a study conducted in 1990 suggests that there
are serious problems associated with some commercial probiotic preparations.
Researchers analyzed 11 products claiming to contain L. acidophilus
in powder, capsule and tablet form for number and type of bacteria present.
Only two of the products were found to contain L. acidophilus, while
the remainder contained L. casei. Problems with culture viability and
contamination with enterococcus and clostridium were also found.
In addition
to selecting viable strains, the method of packaging and storing of
the product is important in maintaining viability. Temperature,
moisture, light and air can all adversely impact viability. These variables
can be controlled through the use of amber glass containers to prevent
entry of oxygen, moisture and light. Most importantly, refrigeration
of the product from the time of manufacture through delivery and storage
is critical in ensuring the potency of the bacterial strains.
Bioactive proteins
Bioactive
proteins are another class of supportive substances that qualify as
probiotics because they may beneficially affect intestinal microbial
balance. Secretory immunoglobulin A (IgA) is the predominant antibody,
or immune protein, the body manufactures and releases in external secretions
such as saliva, tears and milk, and through the epithelial cells lining
the intestine out into the lumen. It plays a major
role in the defense mechanism on the surface of the intestine by preventing
the absorption of, and by disposing of, microbial antigens.
Mucosal IgA also neutralizes viruses and, in the case of bacterial infections,
blocks the attachment of pathogens to mucosal tissues and cells.
Other immune proteins, such as immunoglobulin M (IgM) and especially
immunoglobulin G (IgG), may also be helpful because they are known to
have remarkably similar specificities.
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