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Abstract
The role of probiotic organisms as alternative or complementary therapy in combating large number of gastro
intestinal disorders and their ability to enhance immune response attracts global attention. In addition, their
therapeutic use towards cholesterol-lowering activities has further increased their applications as effective probiotics
for humans as supplements in milk and yoghurt, since there are no other supplements for hypercholesterolemia,
which is the crucial risk factor for cardiovascular diseases. Changes in dietary habits, stressful life and lack of
physical activities are the precursors for increasing incidences of hypercholesterolemia and subsequently
cardiovascular diseases. The present review focuses on some of the animal studies and clinical trials conducted with
probiotic lactobacilli and bifidobacteria. This review may throw some light to prove the ability of these probiotics as a
novel alternative or adjuvants to chemical drugs to help fight hypercholesterolemia.
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Review Article Biology and Medicine, Vol 1 (4): Rev4, 2009
gastrointestinal environment may very well be (McNamara and Sabb, 1989; Suckling et al.,
altering a condition that nature never intended to 1991). With the emergence of a more health-
alter. The short- and long-term effects of this conscious society, the role of probiotic food
change may be difficult to evaluate given the products has gained attention from consumers
multifactorial nature of the gastrointestinal and producers (Perdigon et al., 1991). In this
environment (Brown and Valiere, 2004). respect, the ingestion of probiotic lactic acid
bacteria might be a more natural way to
Risk Factors: Obesity and Hypercholesterolemia decrease serum cholesterol in humans (Taranto
et al., 1999).
Weight gain beyond normal limits and obesity is
a significant problem in both developing and Cholesterol Biosynthesis and Uptake
developed countries. It is estimated that there Although humans synthesize cholesterol to
are roughly 40 to 50 million overweight subjects maintain minimum levels for biological
in India as on today and the obesity has reached functioning, diet also is known to play a role in
epidemic proportions in India affecting 5% of the serum cholesterol levels. The extent of influence
country's population. Obesity is not only a varies significantly from person to person. HDL
physiological disorder but also is the root cause cholesterol, known as good cholesterol, is an
of several diseases and pose increased risk of important scavenger of surplus cholesterol by
health problems such as cardiovascular disease, transporting it from cell membrane to the liver,
hypertension, diabetes, arthritis and certain type where it is degraded or converted into bile acids.
of cancers (American Academy of Pediatrics). In The increase in HDL cholesterol level is known
spite of the fact that cholesterol is the main lipid to have protective effect on the risk of coronary
found in blood, bile and brain tissues it is heart disease. A number of mechanisms
required for the formation of sterols and cellular involving cholesterol itself and a number of
membranes. It is well known that higher levels of hormones regulate the synthesis, uptake and
serum cholesterol are generally considered to metabolism of cholesterol. HMG-CoA Reductase
be a risk factor for coronary heart disease. is a key reaction in the biosynthesis of
cholesterol.
Hypercholesterolemia occurs when there is an
elevated level of total cholesterol in the Bile and Cholesterol
bloodstream. It is the result of high levels of low-
Bile is a yellow-green aqueous solution whose
density lipoprotein (LDL) as compared to high-
major constituents include bile acids,
density lipoprotein (HDL) cholesterol. LDL, the
cholesterol, phospholipids, and the pigment
‘bad’ cholesterol, leaves behind fatty deposits or
biliverdin (De Smet et al., 1994; Hofmann,
plaques in the blood vessels. Accumulation of
1994). It is synthesized in the pericentral
these plaques congests blood vessels and
hepatocytes of the liver, stored and
blocks blood supply to the organs. HDL, the
concentrated in the gallbladder inter-digestively,
‘good’ cholesterol, cleans up excess cholesterol
and released into the duodenum after food
from the body, thus minimizing the amount of
intake. Bile functions as a biological detergent
congestion and blockage. Hypercholesterolemia
that emulsifies and solubilizes lipids, thereby
hardens and narrows blood vessels in various
playing an essential role in fat digestion. This
parts of the body, leading to fatal diseases such
detergent property of bile also confers potent
as chest pains, heart attack and stroke. Blocked
antimicrobial activity, primarily through the
blood vessels in the limbs can cause pain,
dissolution of bacterial membranes (Begley et
ulcers, infections and gangrene.
al., 2005). The primary bile acids, cholic and
chenodeoxycholic acid are synthesized de novo
During the last few decades, numerous in the liver from cholesterol. The solubility of the
epidemiological, laboratory, and clinical studies hydrophobic steroid nucleus increases by
have demonstrated a connection between high conjugation of an N-acyl amidate with either
serum cholesterol and increased risk for
glycine (glycoconjugated) or taurine
atherosclerosis and coronary heart disease, the
(tauroconjugated) prior to secretion. The
latter being a major cause of death in Western resulting molecules are therefore amphipathic
countries (Barr et al., 1951). Potential and can solubilize lipids to form mixed micelles.
hypocholesterolemic pharmaceuticals and food
Bile acids are efficiently conserved under normal
products are continuously being developed to conditions by a process termed enterohepatic
control hypercholesterolemia in humans
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Review Article Biology and Medicine, Vol 1 (4): Rev4, 2009
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Review Article Biology and Medicine, Vol 1 (4): Rev4, 2009
and BSH activity towards bile mixtures that fructooligosaccharide (FOS) and inulin, in order
resembled the human bile, and may be a to determine probiotic activity that would remove
promising candidate to exert beneficial bile the highest level of cholesterol. The
deconjugation activity in vivo. concentration of L. casei ASCC 292 had the
most significant quadratic effect on all responses
The study performed by Kim and coworkers studied. In another study by same workers in
(2008) characterized the factors responsible for 2006, the effectiveness of 3 synbiotic diets [(a)
the cholesterol reduction by Lactobacillus containing Lactobacillus casei ASCC 292 and
acidophilus ATCC 43121. The results showed fructooligosaccharides (LF diet), (b) containing
that the cell-free supernatant (CFS) produced by L. casei ASCC 292 and maltodextrin (LM diet),
ATCC 43121 in the presence of bile salts could and (c) containing L. casei ASCC 292,
also reduce the cholesterol in the broth, unlike fructooligosaccharide, and maltodextrin (LFM
previous reports which suggested a mechanism diet)] were evaluated to reduce serum
by live cells only. cholesterol in male Winstar rats. Results from
this study showed that the synbiotic diet that
Lactobacillus plantarum contained L. casei ASCC 292, fructo-
oligosaccharide, and maltodextrin beneficially
In a study conducted by Nguyen et al., (2007), a altered cholesterol levels and produced a
strain of Lactobacillus plantarum, L. plantarum healthier bowel microbial population without
PH04 was fed to hypercholesterolemic mice with translocation of lactobacilli to other organs
107 CFU per mouse per day for 14 days. (Liong and Shah, 2006).
Compared with a control group, the serum
cholesterol and triglycerides were respectively Similarly, four selected Lactobacillus casei
7% and 10% lower in the group fed L. plantarum strains were examined by Minelli et al. (2004) for
PH04 and fecal lactic acid bacteria increased their potential use as novel probiotics in rats by
while no other significant differences (P < 0.05) evaluating their technological performances,ie
in body weight, visceral weigh index or bacteria in vitro adhesion capacity and intestinal transit
translocation between two groups were tolerance after oral administration in fermented
observed. The results indicated that L. milks. Serum, tissue and faecal samples were
plantarum PH04 could be effectively used as a analyzed before and during treatments. In
probiotic with cholesterol-lowering activities. In treated rats it was reported that the levels of
another study made by Ha et al., (2006) serum triglycerides, cholesterol, transaminase
Lactobacillus plantarum strains were isolated and total bilirubin decreased. In addition,
from human faeces and evaluated for bile salt microbiological and haematological parameters
hydrolase (BSH) production and its effects on indicated that all four L. casei strains presented
serum cholesterol level. The cholesterol favourable strain-specific properties for their
lowering effect by L. plantarum CK 102 could be utilization in functional, health-favouring foods
utilized as an additive for health-assistance (Minelli et al., 2004). Kawase et al.(2000)
foods. In conclusion, these results suggest that reported a decrease of triglyceride levels in
the L. plantarum strains could be used humans by with combined supplementation of L.
commercially as a Probiotic with sound casei and S. thermophilus.
cholesterol lowering activity.
Lactobacillus bulgaricus
Lactobacillus casei Lactobacillus bulgaricus is known to everyone
Initial studies in poultry have demonstrated the as dairy starter bacteria that make yoghurt (a
ability of food fermented or inoculated with type of fermented milk) in symbiosis with
Lactobacillus casei and other lactic acid bacteria Streptococcus thermophilus. Lactobacillus
to significantly lower serum levels of total bulgaricus is an acid-producing bacterium and in
cholesterol and/ or LDL (Mohan et al., 1996). general, it occurs in dairy products and some
Takeshi (2003) reviewed the biological activities plant products. In 1979, the first trial to evaluate
of L. casei that favorably influenced human the effects of lactic acid bacteria on serum
health. Liong and Shah, (2004) evaluated the cholesterol levels in human subjects was
combination of Lactobacillus casei ASCC 292 conducted. Fifty four volunteers participated in a
and six prebiotics, namely, sorbitol, mannitol, randomised cross over trial; the results of which
maltodextrin, high-amylose maize, revealed reductions of between 5-10% in serum
cholesterol levels after several weeks of
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Review Article Biology and Medicine, Vol 1 (4): Rev4, 2009
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Review Article Biology and Medicine, Vol 1 (4): Rev4, 2009
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Review Article Biology and Medicine, Vol 1 (4): Rev4, 2009
gastrointestinal tract (Chikai et al., 1987; Walker deconjugating bile salts that then affect
and Gilliland, 1993; De Smet et al., 1994). It has cholesterol metabolism.
also been suggested that BSH activity should be
a requirement in the selection of probiotic
Future Perspectives
organisms with cholesterol-lowering properties,
as non deconjugating organisms do not appear
to be able to remove cholesterol from the culture Gill and Guarner (2004) reported that there is
medium to any significant extent (Tahri et al., unequivocal evidence that administration of
1996, 1997). probiotics could be effective in the treatment of
acute infectious diarrhoea in children and the
prevention of antibiotic associated diarrhoea and
Effect of Fermented Dairy Products in
nosocomial/community acquired diarrhoea.
Lowering Of Blood Cholesterol
Mann and Spoerry (1974) were the first to report
The future will see the development of new,
that consumption of fermented milk was well-characterized, scientifically proven probiotic
associated with reduced serum cholesterol strains with specific health benefits. There are
levels in the Maasai people. This stimulated enough evidences to support the beneficial
much interest in the cholesterol lowering effects effects of probiotics on hosts over a wide range
of fermented milks and lactic acid bacteria. of clinical conditions. However, some issues like
Several animal studies have shown that
dosage and viability of probiotic strains,
administration of fermented milks or specific industrial standardization and safety aspects
strains of lactic acid bacteria are effective in
need to be dealt with. At present, cholesterol,
lowering blood cholesterol levels. Studies in
cancer and immunology are the three major
human subjects, however, have yielded areas of research on probiotics. Genetic
conflicting results. The most frequently used engineering and other approaches are being
probiotics found in dairy-based food products used to enhance the beneficial effects of
are Lactobacilli and Bifidobacteria. Since these
probiotic microbes. Supplementation of
belong to the indigenous human microflora, they
promising strains of probiotic organisms may
have a long history of safe use and there are offer exciting solution to minimize the problem of
evidences to support their positive roles, some high cholesterol levels in human beings.
of these have been designated as GRAS
However, extensive research is required to
(generally regarded as safe) by the FDA (Food
screen the potent probiotic strains and their
and Drug Administration) due to their long evaluation for the effective management of good
history of use in food fermentations (Teitelbaum
and bad cholesterol in the body and the
and Walker, 2002).
sustainability of the desired results. In addition to
the clinically proven benefits (grade A
Human and animal studies have suggested that recommendations) described above, the use of
the use of dairy products fermented with probiotics for the prevention and management of
probiotics (lactic acid bacteria and over expressed immune function such as atopy
bifidobacteria) may reduce serum lipid levels and inflammatory bowel diseases, and for
(Meydani and Ha, 2000; de Vrese et al., 2001; enhancing immune function and improving
Heyman, 2001) Two studies with normal- efficacy of vaccines in population groups with
lipidemic subjects reported that probiotic less than optimum immune functions (for
administration resulted in a reduction in serum example, infants, elderly, immunocompromised)
triglycerides (19% and 27%, respectively), along hold great promise.
with slight changes in serum total and LDL
cholesterol.94 The proposed mechanism by Treatment with microencapsulated LF11976
which probiotics may decrease serum
formulation produces significant reductions in
cholesterol is suggested to be related to the
serum total cholesterol, LDL cholesterol, and
fermentation of indigestible dietary serum triglyceride levels in diet-induced
carbohydrates. Products of bacterial hypercholesterolemic hamsters. Findings
fermentation, specifically short-chain fatty acids,
suggest the potential of the oral
may inhibit cholesterol synthesis in the liver microencapsulated probiotic cell formulation as
and/or mobilize plasma cholesterol to the liver a functional nutritional alternative for managing
(Rafter, 2002) Some gastrointestinal bacteria excessive serum cholesterol and triglyceride
may also prevent cholesterol absorption by levels (Bhathena J, Martoni C, Kulamarva A et al
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Review Article Biology and Medicine, Vol 1 (4): Rev4, 2009
2009). With the increased evidence of multidrug Brown AC, Valiere A (2004) Probiotics and medical
resistance among pathogens and a continued nutrition therapy. Nutr Clin Care. 2004 Apr-
failure to manage gastrointestinal virus Jun;7(2):56-68.
infections, plus a desire by consumers to use
natural methods for health maintenance rather Bortolini, O., A. Medici, and S. Poli. 1997.
than long-term chemotherapeutic agents, the Biotransformations on steroid nucleus of bile acids.
time is right for probiotics to be taken seriously. Steroids 62:564–577.
It is also time for scientists to provide the data,
Carey, M. C., and W. C. Duane. 1994. Enterohepatic
which give a basis and mechanism of action for
circulation, p. 719–738. In I. M. Arias, N. Boyer, N.
the human utilization of well-studied organisms. Fausto, W. B. Jackoby, D. A. Schachter, and D. A.
Shafritz (ed.), The liver: biology and pathobiology.
Acknowledgements Raven Press, Ltd., New York, N.Y.
We are grateful to the management of Unique
Chikai, T., H. Naka, and K. Ushida. 1987.
Biotech for providing the facilities and NIN for
Deconjugation of bile acids by human intestinal
useful suggestions. bacteria implanted in germ-free rats. Lipids 22:669–
671.
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Table-1
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Figure-1
Source - Internet
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