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Dairy and Food Culture Technologies, Littleton, CO 80122-2526
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ABSTRACT |
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 TOP ABSTRACT Probiotic definition, scientific...Probiotic influence on human...Probiotic products in the...SUMMARYREFERENCES |
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KEY WORDS: • probiotic • Lactobacillus • Bifidobacterium
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Probiotic definition, scientific basis and rationale |
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TOPABSTRACTProbiotic definition, scientific...Probiotic influence on human...Probiotic products in the...SUMMARYREFERENCES |
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), and the interactions of these colonizing
microbes with the host are nothing if not complex. Studies from
germ-free animals have proven that animals do not require microbial
colonization for survival, but germ-free animals, compared with
their conventional counterparts, demonstrate many physiologic and
biochemical differences and are more susceptible to infection
(Tannock 1998
). This is attributed to a poorly primed
immune system and perhaps the absence of what has been termed
"competitive colonization" (van der Waaij et al. 1972
). Competitive colonization is a term describing the
interference of virulence by invading pathogens by commensal microbes.
The differences between conventional and germ-free animals have
provided a basis for the belief that microbial colonization has
important health implications for humans. On rare occasions, microbes develop a pathogenic relationship with a host, and illness or death of the host can result. Negative influences on human health by colonizing or invading microbes need not be acute. Microbial metabolites may possess genotoxic, mutagenic or carcinogenic activity and contribute subsequently to the development of cancer over a period of long-term exposure. It is the recognition of the effects of colonizing microbes in association with the human body, and the combination of wanting to encourage the positive and discourage the negative activities of commensal and invading microbes that have led to the probiotic theory.
Probiotics have been defined as live microorganisms that confer a
health effect on the host when consumed in adequate amounts
(Guarner and Schaafsma 1998
). The concept of probiotics
evolved from a theory first proposed by Nobel Prize winning Russian
scientist, Elie Metchnikoff (Metchnikoff 1908
),
who suggested that the long life of Bulgarian peasants resulted from
their consumption of fermented milk products. He believed that when the
bacillus was consumed, it carried out the fermentation of this product,
positively influencing the microflora of the colon by decreasing the
toxic effects of colonic microflora. This concept was developed further
through the decades, and today, especially in Europe and Japan,
probiotic-focused research, product development and marketing are
at an all-time high.
The field of scientific investigation of probiotics is laced with
inadequately understood but interesting findings that are difficult to
interpret with respect to consumption by a reasonably healthy general
population. Research on probiotics consists of experiments done with
dozens of different bacterial strains and combinations of strains used
at different doses in in vitro, animal or human studies with dozens of
different research end points. The positive results from human
volunteer or clinical studies, even in the absence of compelling
mechanistic studies, provide validity to the probiotic concept. The
backdrop to these efforts is the rapidly expanding marketing worldwide
of probiotic-containing products. Experts in this field acknowledge
that a prerequisite for successful probiotic research and development
is developing fundamental knowledge of intestinal bacteria and their
interactions with each other and their host (Tannock 1999
).
Are these efforts to understand the role probiotic bacteria may play in human health justifiable apart from the interest in yet another functional ingredient to lure purchasing dollars from an increasingly health conscious U.S. consumer? Are benefits from these bacteria going to make a substantive difference in the health of the average consumer? At this point, the responses to these questions are speculative. However, the emergence of some new public health risks suggests ways in which effective probiotic bacteria may play an important role in maintaining human health.
Some infections, once thought to be benign and self-limiting or
readily treatable with antibiotics, are now recognized as more serious
health threats. Campylobacter jejuni, now believed to be
the leading cause of bacterial gastroenteritis (Altekruse et al. 1999
), results in Guillain-Barré syndrome (leading to
acute neuromuscular paralysis) in 0.1% of cases. Reiter syndrome, a
reactive arthritis, can also occur. Other foodborne pathogens have
become prevalent and life-threatening, including Shiga-like
Escherichia coli strains. Multiple antibiotic resistance
is a continual threat in the battle against once treatable infections.
Vaginosis is now recognized to be associated with low-birth-weight
infants, preterm delivery and increased risk for sexually transmitted
disease (Hillier et al. 1995
, Klebanoff and Coombs 1991
, Sweet 1995
). Demographic trends
have indicated the increase in populations of the immunocompromised,
including the elderly, those suffering from AIDS, organ transplant
recipients, chemotherapy patients and many others. In the
nonindustrialized nations, infections such as rotavirus claim the lives
of millions of infants each year (Parashar et al. 1998
).
Because of these emerging microbial threats, a safe, low risk approach
that adds a barrier to microbial infection or to the negative
influences of indigenous colonizing microbes may be significant to
human health.
Probiotic bacteria have been suggested to play a role in a variety of
health effects, and mechanisms proposed for mediating these effects are
numerous (Table 1
). In addition to their proposed direct effects on humans, probiotics
may also have implications for human health by their use in animal
agriculture. Probiotics have been tested for preventing colonization of
food animals, and the products derived from them, with pathogens of
animal origin. One product, developed by the USDA and called PREEMPT,
blends 29 intestinal bacteria from chickens and is effective at
protecting chickens from colonization by Salmonella,
E. coli O157:H7, Campylobacter, and
Listeria (USDA Press Release 0122.98, March 19, 1998).
Animal agriculture may also benefit from the improved efficiency that
results from greater resistance of farm animals to infectious diseases,
increased growth rate, improved feed conversion and increased yield of
milk and eggs (Fuller 1998
).
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, Sanders and Huis in’t Veld 1999
, Tannock 1999
) and are
recommended for more in-depth coverage of this area. |
Probiotic influence on human health |
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TOPABSTRACTProbiotic definition, scientific...Probiotic influence on human...Probiotic products in the...SUMMARYREFERENCES |
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). Epidemiology.
Nutritional epidemiology has provided many insights into the
association of dietary factors and risk of disease. It is powerful in
identifying strong links between risk factors and disease; however,
subtle associations are more difficult to identify through this means
(Langseth 1996
). The complex and interdependent nature
of dietary choices also makes these studies difficult. Even recognizing
these limitations, epidemiologic links through cohort or
case-controlled studies between probiotics and health would provide
powerful support for the probiotic theory. Unfortunately, little
epidemiologic evidence exists relating probiotics or
probiotic-containing foods and disease incidence. These studies
would be difficult to control in a manner consistent with our knowledge
of probiotic function. Important parameters such as specific strain and
dose would be unknown for most probiotic-containing food products.
A few case-controlled studies have been conducted to evaluate the
effects of yogurt or fermented milks on some cancer rates. However,
neither the type nor level of probiotic bacteria consumed was evaluated
in these studies, even though each may have a significant effect on
results. Monique et al. (1986)
found an inverse
relationship between frequency of yogurt consumption and risk of breast
cancer in France (1010 breast cancer cases and 1950 controls).
Peters et al. (1992)
found yogurt to be a protective
factor in a case-controlled study of colon cancer incidence in Los
Angeles County (746 cases, 746 controls). A case-controlled study
of breast cancer in the Netherlands (van’t Veer et al. 1989
) also suggested that fermented dairy products could be
protective (133 cases and 289 controls), although Kampman et al. (1994)
did not find a similar relationship between fermented
dairy products and colorectal cancer. One intervention trial did show
that the recurrence rate for superficial bladder cancer was lower for
subjects receiving freeze-dried Lactobacillus casei
Shirota than a placebo (Aso and Akazan 1992
).
More such studies will be important in clarifying the role probiotic
products play in cancer rates.
In a more general evaluation than that of studies focused on fermented
dairy products, a review of 89 epidemiologic studies on dairy foods in
general and cancer (prostate, breast, colorectal and others) suggested
that there is no significant association (positive or inverse) of dairy
food consumption and any cancer, with the possible exception of
prostate cancer (Jain 1998
). Although prostate cancer
incidence showed a weak correlation with milk consumption, available
studies were deemed inconclusive. The author concluded that, in
balance, current epidemiologic data cannot support a protective or
promotional role of dairy foods in cancer rate. Contributing to this
conclusion may be the compounding influence of potentially negative
components of dairy foods (saturated fat) and putative positive
components (bacterial cultures, vitamin D, calcium, conjugated linoleic
acids, sphingolipids).
Focused epidemiologic studies using populations consuming defined
probiotic products over a long period of time are required to
supplement the in vitro and animal studies that suggest a protective
influence of probiotic bacteria against cancer. Mechanisms thought to
play a role in probiotic-mediated protection of cancer are shown in
Table 2
(Rafter 1995
).
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Although 50 million Americans have been diagnosed with hypertension and
its negative effect on health is well documented (Mayo Clinic Web Site,
www.mayohealth.org), little is known about any role probiotic
bacteria may play in controlling hypertension. One line of research has
suggested that bioactive peptides resulting from the proteolytic action
of probiotic bacteria on casein (milk protein) during milk fermentation
may suppress the blood pressure of hypertensive individuals
(Takano 1998
). Preliminary studies with spontaneously
hypertensive rats (Nakamura et al. 1995
and 1996
) and
one human clinical study (Hata et al. 1996
) provide the
evidence. Two tripeptides, valine-proline-proline and
isoleucine-proline-proline, isolated from a dairy-based
fermentation of milk by Saccharomyces cerevisea and
Lactobacillus helveticus have been identified as the active
components. These tripeptides function as angiotensin-I–converting
enzyme inhibitors and reduce blood pressure. The Japanese company,
Calpis (Kanagawa, Japan), has developed a pasteurized product based on
this technology, Ameal-S, which has functional food status in
Japan. Unlike many other probiotic-induced effects, it is important
to note that this effect is mediated by a fermentation end product, not
viable probiotic cells themselves.
Another antihypertensive activity was associated with cell wall
fragments of L. casei YIT9018 (Sawada et al. 1990
). In a placebo-controlled trial with 28 human
hypertensive subjects, powdered cell extracts (not viable cells) were
administered orally and effects on systolic pressure, diastolic
pressure and heart rate were determined. Small, but significant
decreases in all three were noted.
An interesting characteristic of these activities is that neither requires viable cells, and they provide novel mechanisms for probiotic-mediated effects. Taken together, they suggest that probiotic bacteria may be effective in mediating an antihypertensive effect.
Urogenital infections.
A frequent source of pathogens for urinary and vaginal tract infections
in women is the intestinal tract. Pathogens linked to vaginal
infections include Trichomonas, Candida or mixed
bacterial infections involving Gardnerella vaginalis and
Mycoplasma hominis (Spiegel 1991
). Urinary
tract infections are caused by anaerobic gram-negative rods,
E. coli, Chlamydia and Candida
(Reid et al. 1998
). Although effective therapies for
curing these infections are available, these infections, once thought
benign, can in fact have serious side effects. Vaginal infections are a
risk factor for low-birth-weight infants, preterm delivery, pelvic
infections leading to infertility and susceptibility to sexually
transmitted diseases (Hillier et al. 1995
, Sweet 1995
). Furthermore, urinary tract and vaginal infections can be
recurrent, suggesting that current therapies could be augmented by a
prophylactic approach.
A healthy vaginal tract is associated with high populations of
lactobacilli (especially hydrogen peroxide–producing lactobacilli) and
a pH < 5.0 (Eschenbach et al. 1989
, Hawes et al. 1996
, Hillier et al. 1992
,
Klebanoff et al. 1991
). This fact, coupled with the
intestinal route of transmission of bacteria to the urogenital tract,
has led to the theory that oral probiotics may be useful in treatment
or prevention of urogenital infections.
Clinical evaluations have been conducted on the influence of
lactobacilli on treatment of bacterial vaginosis using intravaginal
suppositories and for prevention of recurrent candidal and bacterial
vaginal infections (Mallen et al. 1992
). Several of
these studies have suffered from small numbers of subjects or failure
of enrolled subjects to complete the study. Although Nyirjesy et al. (1997)
concluded that alternative medicines are unlikely to
be of benefit to those with chronic vaginal symptoms, several studies
do suggest that administration of lactobacilli, either orally or
intravaginally, can play a prophylactic role in the etiology of this
disease, presumably through the recolonization of the vaginal tract
with lactobacilli (Hallen et al. 1992
, Hilton et al. 1992
and 1995
, Shalev et al. 1996
). In a
crossover trial of 46 patients, Shalev et al. (1996)
compared the ability of ingestion of yogurt containing live L.
acidophilus (1.5 x 1010/d) with
pasteurized yogurt to prevent vaginal infections [bacterial vaginosis
(BV) and cadidiasis]. Unfortunately, only seven patients completed the
entire study protocol. Significant differences were seen in BV
infections in those consuming live yogurt compared with pasteurized
yogurt or no yogurt. Candida infections were decreased
during yogurt consumption regardless of the presence of live or
heat-killed lactobacilli. Hilton et al. (1992)
studied the effect of yogurt consumption on Candida
vaginitis in a crossover trial with 33 women (13 completed the study).
Results indicated a threefold decrease in infections in patients
consuming yogurt containing L. acidophilus
(>1010/d). A commercial freeze-dried
L. acidophilus suppository was administered twice daily for
6 d to women suffering from BV in a placebo-controlled trial
(Hallen et al. 1992
). After treatment, the patients
using the Lactobacillus preparation showed a lower level
(43%) of BV than did the placebo group (100%), although the effect
was short lived (relapse after menstruation).
Lactobacillus applications in urinary tract infections have
been evaluated, but not as yet with the use of an oral vehicle of
delivery (Reid et al. 1998
). Weekly, intravaginal
instillations of dried lactobacilli (>109
colony-forming units/dose) in 10 premenopausal women resulted in
the reduction of urinary tract infections from 6.3 per patient in the
year before the study, to 1.3 per patient during the study (Reid and Bruce 1995
). The mean vaginal pH was 4.8 during the study
compared with 5.0 before the study. Reid et al. (1995)
reported extended similar results, including 38 women who completed the
study. These results suggest that vaginal lactobacilli can decrease the
risk of urinary tract infections.
Taken together, these studies suggest a positive role for lactobacilli
in controlling vaginal and urinary tract infections in women, and
suggest that externally applied probiotic preparations given orally or
intravaginally may provide a therapeutic source of lactobacilli to help
prevent infections. The lack of negative side effects, the emphasis on
prevention rather than cure and the "natural" image surely are
positive characteristics of this approach. Hughes and Hillier (1990)
concluded that many commercially available foods and
dietary supplements containing lactobacilli may be inadequate for
vaginal applications. Their conclusions, based largely on the report of
improper species being present in the products, must be reconfirmed
using modern genetic technologies for lactobacilli (Tannock 1999
). Continued research focused on selection of the proper
strains for these applications, development efforts to provide products
that deliver efficacious levels of these bacteria and clinical trials
that substantiate effects will improve the likelihood that probiotics
will be used in preventing these infections and their consequences in
women.
Lactose intolerance.
The inability of adults to digest lactose is widespread, although those
deficient in lactase generally tolerate lactose better from yogurt than
from milk (Savaiano and Kotz 1988
, Shah 1993
, Suarez et al. 1995
). The effect of lactose
maldigestion has been studied by measuring breath hydrogen excretion
(Levitt and Donaldson 1970
), which has been correlated
with colonic fermentation and lactose maldigestion. As accepted as this
method is, however, it does not provide a complete understanding of the
lactose maldigestion situation because in some cases, the absence of an
effect on breath hydrogen has been correlated with improved
symptomatology (Montes et al. 1995
, Savaiano et al. 1984
). The contribution of lactase by the bacterial
cultures used to manufacture the yogurt is thought to mediate enhanced
lactose digestion; this is evidenced by the inability of pasteurized
yogurt or yogurts containing a low cell count to reduce breath hydrogen
excretion, although pasteurized yogurt does improve gastrointestinal
symptoms (Savaiano et al. 1984
). Slower gastric emptying
of yogurt compared with milk has also been hypothesized to play a role.
In general, results have indicated that yogurt starter cultures
(Streptococcus thermophilus and Lactobacillus
delbrueckii subsp. bulgaricus), present at levels
normally seen in yogurt (
108/g), effectively
improve the digestion of lactose in lactose maldigesters. The effect
seems to be more cell-density dependent (Lin et al. 1991
) than strain specific (Martini et al. 1991
,
Vesa et al. 1996
), suggesting that, in general, most
commercial strains of these bacteria likely possess the physiologic and
biochemical characteristics necessary for mediating this effect.
Defining what exactly these characteristics are, however, has been a
research challenge. Total lactase levels in yogurts have not correlated
well with breath hydrogen results in human subjects. Martini et al. (1991)
found that yogurts made from several different
yogurt starters were equivalent in effect, even though total
ß-galactosidase activity of two of the yogurts studied varied as much
as threefold. Kotz et al. (1994)
found a similar lack of
correlation between reduction in breath hydrogen excretion and lactase
content of yogurts. Wytock and DiPalma (1988)
reported a
difference in effectiveness among commercial yogurts, but no
microbiological or enzymatic characterization of the yogurt was
conducted in this study, thus making it difficult to judge these
results.
The results on probiotic bacteria (L. acidophilus,
bifidobacteria, among others) are less clear cut. Studies suggest that
some dairy products formulated exclusively with probiotic bacteria
(e.g., Sweet Acidophilus milk) are not effective (Payne et al. 1981
). The low probiotic cell count (~2 x 106/mL) in these products presumably contributes
to this result. Research also suggests that the physiologic
characteristics of these probiotic bacteria may not be as suited to
mediating this effect as are the starter cultures. For example, it has
been suggested that bacterial cell permeablization in the small
intestine after exposure to bile improves lactose digestion by
increasing contact between ingested lactose and lactase. Yogurt starter
cultures are bile sensitive, whereas probiotic lactobacilli and
bifidobacteria are generally bile resistant. Vesa et al. (1996)
tested three semisolid fermented dairy products, all
containing S. thermophilus levels
>108/g, with two of the three products also
containing L. acidophilus and Bifidobacterium.
Results indicated no difference in lactose digestion although a
fourfold difference in lactase activity was present, leading
investigators to attribute enhanced lactose digestion to slower gastric
emptying, not microbial lactase.
The roles of bile resistance, acid resistance, cell membrane permeability, specific activity of microbial ß-galactosidase and the stability of these factors during storage and on transit through the gastrointestinal tract on alleviation of symptoms of lactose maldigestion must be clarified further to achieve a fuller understanding of the role of starter and probiotic bacteria in enhancing lactose digestion.
Cholesterol.
Elevated levels of certain blood lipids are a risk factor for
cardiovascular disease. The observation that conventional animals
excrete higher levels of cholesterol in feces than germ-free
animals suggests that colonizing microbes may influence serum
cholesterol levels (Eyssen 1973
). The body of research
on the effects of culture-containing dairy products or probiotic
bacteria on cholesterol levels has yielded equivocal results
(Taylor and Williams 1998
). Since 1974, 13 studies have
been published evaluating blood lipids in human subjects consuming
fermented milk products, with a total of 465 subjects (302 of those
subjects were in three studies). Statistically significant lowering of
total cholesterol ranged from 5.4 to 23.2% and of LDL cholesterol from
9 to 9.8%. The studies conducted to date have been criticized for
failure to stabilize baselines before the onset of the feeding
protocol, small sample size, short study duration, unreasonably large
fermented milk intake requirements and failure to control for diet and
physical activity of subjects. Of the studies showing significant
results on the lowering of either total cholesterol or LDL, the
duration did not exceed 6 wk. One study showed increases in both total
cholesterol and LDL cholesterol (Rossouw et al. 1981
).
The mechanisms for and effect of probiotic bacteria on reduction of
serum cholesterol are unknown. One hypothesis suggests that some
strains of L. acidophilus can assimilate the cholesterol
molecule (Gilliland et al. 1985
). This hypothesis has
been tested in laboratory assays (Gilliland et al. 1985
,
Rasic et al. 1992
). A criticism of this hypothesis
questions the physiologic relevance of assimilation kinetics observed
in an in vitro, aqueous assay conducted at pH 6.0 or lower. Rather than
assimilation, it has been suggested that the pH-dependent,
transient cholesterol precipitation in laboratory media caused the
effects (Klaver and Meer 1993
, Tahri et al. 1996
). Another proposed mechanism is based on the ability of
certain probiotic lactobacilli and bifidobacteria to deconjugate bile
acids enzymatically, increasing their rates of excretion (De Smet et al. 1994
). Because cholesterol is a precursor of bile
acids, this could lead to reduction in serum cholesterol because
cholesterol molecules are converted to bile acids to replace those lost
through excretion. If this mechanism operated in the control of serum
cholesterol levels, one concern is the conversion of deconjugated bile
acids into secondary bile acids by colonic microbes. These secondary
bile acids are known cancer promoters. A potential increased risk of
colon cancer may outweigh any benefit of reduction of serum cholesterol
levels. This may provide a rationale for the selection of probiotic
strains that are bile salt hydrolase negative, although efforts to the
contrary have been published (du Toit et al. 1998
).
Another mechanism, proposed by Mann (1977)
, postulated
that 3-hydroxy-3-methyl glutaric acid (HMG) present in fermented milk
inhibits hydroxy methyl glutaryl CoA reductase, the rate-limiting
enzyme in cholesterol biosynthesis. These hypotheses have not been
confirmed in animal or human studies, although Gilliland et al. (1985)
established a cholesterol-lowering effect of a
cholesterol-assimilating (but not a nonassimilating) strain in
boars. Further research on any mechanisms should be preceded by
evidence for clinical effect in at least one thoroughly conducted
study.
Other.
Additional probiotic effects have also been proposed, but data are
either too preliminary or beyond the scope of this article. These
include probiotic effects against Helicobacter pylori
infections in the stomach (Coconnier et al. 1998
,
Kabir et al. 1997
, Midolo et al. 1995
),
alcoholic liver disease (Nanji et al. 1994
), small bowel
bacterial overgrowth (Simenhoff et al. 1996
,
Stotzer et al. 1996
), ulcerative colitis (Kruis et al. 1997
), allergy to milk protein (Pelto et al. 1996
), juvenile chronic arthritis (Malin et al. 1996
), antioxidative effects (Ahotupa et al. 1996
), asthma (Wheeler et al. 1997
), hepatic
encephalopathy (Read et al. 1966
) and their use as
vaccine delivery vehicles (Mercenier 1999
).
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Probiotic products in the United States |
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TOPABSTRACTProbiotic definition, scientific...Probiotic influence on human...Probiotic products in the...SUMMARYREFERENCES |
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Probiotic bacteria can be found worldwide in a variety of products, including conventional food products, dietary supplements and medical foods. In the United States, the main outlets for probiotic bacteria are dairy foods and dietary supplements (primarily in the form of capsules, powder or tablets). A survey of domestic culture producers suggests that the retail U.S. market for probiotic dietary supplements is between $10 and 20 million. Although this is not a huge market, it has been growing.
Dairy foods containing probiotic bacteria include most major brands of yogurt, culture-containing fluid milks, such as "Sweet Acidophilus Milk" and a few brands of cottage cheese. Dairy foods seem to fit naturally with probiotics because of the traditional association of beneficial fermentation bacteria and fermented dairy products. Consumers naturally associate fermented dairy products with live cultures and perceive a benefit (albeit undefined) in the presence of these cultures.
In Europe and Japan, in addition to dietary supplements in pill form
and traditional dairy products, hybrid products are also sold. These
products, such as Actimel (Danone, Paris) and Yakult (Yakult, Tokyo),
are sold in small (65–100 mL) individual serving size bottles
containing a milk-based beverage produced by the fermentation of
one or more probiotic bacteria. They are marketed to be consumed daily,
as a food supplement, but are not in a size that would be considered,
at least in the U.S., a significant component of a meal. Their purpose
is to provide a significant dose of functional probiotic bacteria. A
comparison of probiotic products in the U.S. and in Europe can be found
in Sanders and Huis in’t Veld (1999)
.
Active principle.
One issue important to the development and consumption of
probiotic-containing products is the concept of "active
principle." For the most part, it is assumed that the active
component of probiotic products is viable bacteria, and in fact, this
is the only measure of probiotic activity noted on U.S. products today.
In general, the presumption is that probiotic viability is a reasonable
measure of activity. In most cases, even if viability is not required,
it is likely correlated with most effects because it is a useful
indicator of the number of cells present, regardless of what cell
component may be active. However, the literature suggests several
situations in which viability is not required for some activities.
Improved digestion of lactose (Vesa et al. 1996
), some
immune system modulation activities (Hosono et al. 1997
,
Marin et al. 1997
, Perdigon et al. 1986
,
Solis Pereyra and Lemonnier 1993
, Tomioka and Saito 1992
), and antihypertensive effects (Maeno et al. 1996
) have been linked to nonviable cells (cell components,
enzyme activities or fermentation products). Some studies have compared
nonviable cells as controls in clinical evaluations (Hata et al. 1996
, Maeno et al. 1996
, Titze et al. 1996
).
This discussion leads to the conclusion that definition of the active property of a probiotic product is essential to understand shelf-life issues, and efforts to maximize shelf life must be focused on maintaining optimal levels of this ingredient, whether as the intact, viable cell, some cell component(s), a metabolic end product or a combination of these.
Strain specificity of effects.
Not all probiotic bacteria are identical. They differ on the bases of genus, species and even strain. The literature is replete with examples of strain-dependent responses when scientists evaluate characteristics of a multitude of different probiotic bacteria. Strains of the same species could be expected to differ in traits such as stability, expression of enzymes, extent and types of inhibitors produced, carbohydrate fermentation patterns, acid producing ability, resistance to acid and bile, ability to colonize the gastrointestinal tract and, perhaps most importantly, clinical efficacy. Just because strains might differ from one another, it does not necessarily mean that they do. But this microbiological circumstance does impose a burden of proof upon those attempting to commercialize probiotic bacteria. Statements substantiating probiotic activity based on the body of literature on different probiotic strains does not engender a high degree of confidence in the efficacy of inadequately studied strains. Positive research, especially clinical and mechanistic research, conducted on a specific strain is required to prove efficacy. This also contributes substantially to the commercial value of the probiotic strain.
Consumer issues: how do consumers know what they are getting?
In general in the U.S., probiotic-containing food products make no
mention of the numbers of probiotic bacteria present in the product per
serving. Most products list bacterial genera and species added as live
cultures, but not levels. California and Oregon are unique in that they
legislate a minimum requirement for acidophilus-containing fluid
milk products (106/mL). In the U.S., yogurt is
not required to contain any viable cultures. In response, an industry
group, the National Yogurt Association, allows yogurt manufacturers use
of its "Live Active Culture Seal" on products that contain
108 viable cultures per gram at time of
manufacture. However, no distinction is made between yogurt starter
cultures used primarily for acid production (S. thermophilus
and L. delbreuckii subsp. bulgaricus) and
probiotic species (L. acidophilus, L. casei, L. reuteri,
Bifidobacterium species, among others). Therefore, this seal is of
little value in assuring consumers of effective probiotic levels. In
practice, fluid milk products (with their short shelf life and
near-neutral pH) provide the expected levels of probiotic bacteria
(108 viable cultures per gram), even in states
that do not require it. Results from yogurt products show a greater
range in levels of viable probiotic bacteria. Some commercial yogurts
seem to maintain acceptable levels (>107/g)
(Iturriria-Laverty et al. 1999
); others show much lower
levels (Dave and Shah 1997
, Micanel et al. 1997
, Rybka and Fleet 1997
). There is clearly a
need for industry to provide more useful information to consumers on
probiotic content of dairy foods.
Probiotic-containing dietary supplements frequently indicate a viable
count per dose contained in the product at time of manufacture, not at
end of shelf life. Several reports of misleading labeling of dietary
supplements have been published (Hamilton-Miller et al. 1996
and 1999
). Labeling has been criticized for overstating the level
of viable bacteria, for inaccurately indicating the species of
probiotic bacteria present and for the presence of species of bacteria
not listed on the label (e.g., Enterococcus). Clearly, there
is a need for the probiotics industry to focus on delivery of high
potency doses of appropriate bacteria in these products.
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SUMMARY |
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TOPABSTRACTProbiotic definition, scientific...Probiotic influence on human...Probiotic products in the...SUMMARYREFERENCES |
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In the U.S., the market for probiotic products is underdeveloped compared with Europe and Japan. At present, U.S. consumers have little means of determining probiotic levels at time of consumption in probiotic foods and dietary supplements. Probiotics offer a broad range of potential health benefits, but the extent of the effect of specific strains on the health of a generally healthy general population remains to be determined. Equivocal results observed in probiotic efficacy studies in humans may have to do with the testing of ineffective strains or potentially effective strains at doses too low to be effective or poor study design. Research is also required to characterize health benefits further and to define the "active principle" in probiotic preparations.
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TOPABSTRACTProbiotic definition, scientific...Probiotic influence on human...Probiotic products in the...SUMMARYREFERENCES |
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1. Ahotupa M., Saxelin M., Korpela R. Antioxidative properties of Lactobacillus GG. Nutr. Today 1996;suppl.31:51S-52S
2. Altekruse S. F., Stern N. J., Fields P. I., Swerdlow D. L. Campylobacter jejuni–an emerging foodborne pathogen. Emerging Infect. Dis. 1999;5:28-35[Medline]
3. Aso Y., Akazan H. Prophylactic effect of Lactobacillus casei preparation on the recurrence of superficial bladder cancer. BLP study group. Urol. Int. 1992;49:125-129[Medline]
4.
Coconnier M.-H., Lievin V., Hemery E., Servin A. L. Antagonistic activity against Helicobacteri infection in vitro and in vivo by the human Lactobacillus acidophilus strain LB. Appl. Environ. Microbiol. 1998;64:4573-4580
5. Dave R. I., Shah N. P. Viability of yoghurt and probiotic bacteria in yoghurts made from commercial starter cultures. Int. Dairy J. 1997;7:31-41
6. De Smet I., Van Hoorde L., De Saeyer N., Vande Woestyne M., Verstraete W. In vitro study of bile salt hydrolase (BSH) activity of BSH isogenic Lactobacillus plantarum 80 strains and estimation of cholesterol lowering through enhanced BSH activity. Microb. Ecol. Health Dis. 1994;7:315-329
7. Drasar B. S., Hill M. J. Human Intestinal Flora 1974 Academic Press New York, NY.
8. du Toit M., Franz C.M.A.P., Dicks L.M.T., Schillinger U., Haberer P., Warlies B., Ahrens F., Holzapfel W. H. Characterisation and selection of probiotic lactobacilli for a preliminary minipig feeding trial and their effect on serum cholesterol levels, faeces pH and faeces moisture content. Int. J. Food Microbiol. 1998;40:93-104[Medline]
9. Eschenbach D. A., Davick P. R., Williams B. L., Klebanoff S. J., Young-Smith K., Critchlow C. M., Holmes K. K. Prevalence of hydrogen peroxide-producing Lactobacillus species in normal women and women with bacterial vaginosis J. Clin. Microbiol. 1989;27:251-256
10. Eyssen H. Role of gut microflora in metabolism of lipids and sterols. Proc. Nutr. Soc. 1973;32:59-63[Medline]
11. Fonden R., Mogensen G., Tanaka R., Salminen S. Effect of Fermented Dairy Products on Intestinal Microflora, Human Nutrition and Health: Current Knowledge and Future Perspectives 1999 International Dairy Federation Publication Brussels, Belgium. (in press)
12. Fuller R. Probiotics for farm animals. Tannock G. W. eds. Probiotics: A Critical Review 1998 Horizon Scientific Press Wymondham, UK.
13.
Gilliland S. E., Nelson C. R., Maxwell C. Assimilation of cholesterol by Lactobacillus acidophilus. Appl. Environ. Microbiol. 1985;49:377-381
14. Guarner F., Schaafsma G. J. Probiotics. Int. J. Food Microbiol. 1998;39:237-238[Medline]
15. Hallen A., Jarstrand C., Pahlson C. Treatment of bacterial vaginosis with lactobacilli. Sex. Transm. Dis 1992;19:146-148[Medline]
16.
Hamilton-Miller J.M.T., Shah S., Smith C. T. ‘Probiotic’ remedies are not what they seem. Br. Med. J. 1996;312:55-56
17. Hamilton-Miller J.M.T., Shah S., Winkler J. T. Public health issues arising from microbiological and labelling quality of foods and supplements containing probiotic microorganisms. Public Health Nutr 1999;2:223-229[Medline]
18.
Hata Y., Yamamoto M., Ohni M., Nakajima K., Nakamura Y., Takano T. A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am. J. Clin. Nutr. 1996;64:767-771
19. Hawes S. E., Hillier S. L., Benedetti J., Stevens C. E., Koutsky L. A., Wolner-Hanssen P., Holmes K. K. Hydrogen peroxide-producing lactobacilli and acquisition of vaginal infections. J. Infect. Dis. 1996;174:1058-1063[Medline]
20. Hillier S. L., Krohn M. A., Klebanoff S. J., Eschenbach D. A. The relationship of hydrogen peroxide-producing lactobacilli to bacterial vaginosis and genital microflora in pregnant women. Obstet. Gynecol. 1992;79:369-373[Medline]
21.
Hillier S. L., Nugent R. P., Eschenbach D. A., Krohn M. A., Gibbs R. S., Martin D. H., Cotch M. F., Edelman R., Pastorek J. G., Rao A. V., McNellis D., Regan J. A., Carey J. C., Klebanoff M. A. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. N. Engl. J. Med. 1995;333:1737-1742
22. Hilton E., Isenberg H. D., Alperstein P., France K., Borenstein M. T. Ingestion of yogurt containing Lactobacillus acidophilus as prophylaxis for candidal vaginitis. Ann. Intern. Med. 1992;116:353-357
23. Hilton E., Rindos R., Isenberg H. D. Lactobacillus GG vaginal suppositories and vaginitis. J. Clin. Microbiol. 1995;33:1433[Medline]
24. Hosono A., Lee J., Ametani A., Natsume M., Hirayama M., Adachi T., Kaminogawa S. Characterization of a water-soluble polysaccharide fraction with immunopotentiating activity from Bifidobacterium adolescentis M101–4. Biosci. Biotechnol. Biochem. 1997;61:312-316[Medline]
25.
Hughes V. L., Hillier S. L. Microbiological characteristics of Lactobacillus products used for colonization of the vagina. Obstet. Gynecol. 1990;75:244-248
26. Iturriria-Laverty K., Tong P. S., Sanders M. E. Microbiological stability of probiotic and starter bacteria in commercial yogurt and cottage cheese. American Dairy Science Association, Annual Meeting, AbstractD23 1999;:
27. Jain M. Dairy foods, dairy fats, and cancer: a review of epidemiological evidence. Nutr. Res. 1998;18:905-937
28.
Kabir A.M.A., Aiba Y., Takagi A., Kamiya S., Miwa T., Koga Y. Prevention of Helicobcter pylori infection by lactobacilli in a gnotobiotic murine model. Gut 1997;41:49-55
29.
Kampman E., Goldbohm R. A., van den Brandt P. A., van’t Veer P. Fermented dairy products, calcium, and colorectal cancer in the Netherlands cohort study. Cancer Res 1994;54:3186-3190
30.
Klaver F.A.M., Meer R. V. The assumed assimilation of cholesterol by lactobacilli and Bifidobacterium is due to their bile salt-deconjugating activity. Appl. Environ. Microbiol. 1993;59:1120-1124
31.
Klebanoff S. J., Coombs R. W. Viricidal effect of Lactobacillus acidophilus on human immunodeficiency virus type 1: possible role in heterosexual transmission. J. Exp. Med. 1991;174:289-292
32. Klebanoff S. J., Hillier S. L., Eschenbach D. A., Waltersdorph A. M. Control of the microbial flora at the vagina by H2O2 generating lactobacilli. J. Infect. Dis. 1991;164:94-100[Medline]
33. Kotz C. M., Furne J. K., Savaiano D. A., Levitt M. D. Factors affecting the ability of a high ß-galactosidase yogurt to enhance lactose absorption. J. Dairy Sci. 1994;77:3538-3544[Abstract]
34. Kruis W., Schutz E., Fric P., Fixa B., Judmaier G., Stolte M. Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment. Pharmacol. Ther. 1997;11:853-858[Medline]
35. Langseth L. Nutritional Epidemiology. Possibilities and Limitations 1996 International Life Sciences Institute Brussels, Belgium.
36. Levitt M. D., Donaldson R. M. Use of respiratory hydrogen (H2) excretion to detect carbohydrate malabsorption. J. Clin. Lab. Med. 1970;75:937-945[Medline]
37. Lin M.-Y., Savaiano D., Harlander S. Influence of nonfermented dairy products containing bacterial starter cultures on lactose maldigestion in humans. J. Dairy Sci. 1991;74:87-95[Abstract]
38. Maeno M., Yamamoto N., Takano T. Identification of antihypertensive peptides from casein hydrolysate produced by a proteinase from Lactobacillus helveticus CP790. J. Dairy Sci. 1996;73:1316-1321
39.
Malin M., Verronen P., Mykkanen H., Salminen S., Isolauri E. Increased bacterial urease activity in faeces in juvenile chronic arthritis: evidence of altered intestinal microflora?. Br. J. Rheumatol. 1996;35:689-694
40. Mallen A., Jarstrand C., Pahlson C. Treatment of bacterial vaginosis with lactobacilli. Sex. Trans. Dis. 1992;19:146-148
41. Mann G. V. A factor in yoghurt which lowers cholesteremia in man. Atherosclerosis 1977;26:335-340[Medline]
42. Marin M. L., Lee J. H., Murtha J., Ustunol Z., Pestka J. J. Differential cytokine production in clonal macrophage and T-cell lines cultured with bifidobacteria. J. Dairy Sci. 1997;80:2713-2720[Abstract]
43.
Martini M. C., Lerebours E. C., Lin W.-J., Harlander S. K., Berrada N. M., Antoine J. M., Savaiano D. A. Strains and species of lactic acid bacteria in fermented milks (yogurts): effect on in vivo lactose digestion. Am. J. Clin. Nutr. 1991;54:1041-1046
44. Mercenier A. Lactic acid bacteria as vaccines. Tannock G. W. eds. Probiotics. A Critical Review 1999:113-127 Horizon Scientific Press Norfolk, England.
45. Metchnikoff E. The Prolongation of Life 1908 Putmans Sons New York, NY.
46. Micanel N., Haynes I. N., Playne M. J. Viability of probiotic cultures in commercial Australian yogurts. Aust. J. Dairy Technol. 1997;52:24-27
47. Midolo P. D., Lambert J. R., Hull R., Luo F., Grayson M. L. In vitro inhibition of Helicobacter pylori NCTC 11637 by organic acids and lactic acid bacteria. J. Appl. Bacteriol. 1995;79:475-479[Medline]
48. Monique G. Le, Moulton L. H., Hill C., Kramar A. Consumption of dairy produce and alcohol in a case-control study of breast cancer. J. Natl. Cancer Inst. 1986;77:633-636
49. Montes R. G., Bayless T. M., Saavedra J. M., Perman J. A. Effect of milks inoculated with Lactobacillus acidophlus or a yogurt starter culture in lactose-maldigesting children. J. Dairy Sci. 1995;78:1657-1664[Abstract]
50. Nakamura Y., Masuda O., Takano T. Decrease of tissue angiotensin-I-converting enzyme activity upon feeding sour milk in spontaneously hypertensive rats. Biosci. Biotechnol. Biochem. 1996;60:488-489[Medline]
51. Nakamura Y., Yamamoto N., Sakai K., Takano T. Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin-I-converting enzyme. J. Dairy Sci. 1995;78:1253-1257[Abstract]
52. Nanji A. A., Khettry U., Hossein Sadrzadeh S. M. Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver (disease). Proc. Soc. Exp. Biol. Med. 1994;205:243-247[Abstract]
53. Nyirjesy P., Weitz M. V., Grody M.H.T., Lorber B. Over-the-counter and alternative medicines in the treatment of chronic vaginal symptoms. Obstet. Gynecol. 1997;90:50-53[Abstract]
54. Parashar U. D., Bresee J. S., Gentsch J. R., Glass R. I. Rotavirus. Emerg. Infect. Dis. 1998;4:561-570[Medline]
55.
Payne D. L., Welsh J. D., Manion C. V., Tsegaye A., Herd L. D. Effectiveness of milk products in dietary management of lactose malabsorption. Am. J. Clin. Nutr. 1981;34:2711-2715
56. Pelto L., Salminen S. J., Isolauri E. Lactobacillus GG modulates milk-induced immune inflammatory response in milk-hypersensitive adults. Nutr. Today 1996;suppl. 31:45S-46S
57.
Perdigon G, Nader de Macias M. E., Alvarez S., Oliver G., Pesce de Ruiz Holgado A. A. Effect of perorally administered lactobacilli on macrophage activation in mice. Infect. Immun. 1986;53:404-410
58. Peters R. K., Pike M. C., Garabrant D., Mack T. M. Diet and colon cancer in Los Angeles County, California. Cancer Causes Control 1992;3:457-473[Medline]
59. Rafter J. The role of lactic acid bacteria in colon cancer prevention. Scand. J. Gastroenterol. 1995;30:497-502[Medline]
60. Rasic J. L., Vujicic I. F., Skrinjar M., Vulic M. Assimilation of cholesterol by some cultures of lactic acid bacteria and bifidobacteria. Biotechnol. Lett. 1992;14:39-44
61. Read A. E., McCarthy C. F., Heaton K. W., Laidlaw J. Lactobacillus acidophilus (Enpac) in treatment of hepatic encephalopathy. Br. Med. J. 1966;1:1267-1269[Medline]
62. Reid G., Bruce A. W. Low vaginal pH and urinary-tract infection. The Lancet 1995;346:1704
63. Reid G., Bruce A. W., Smeianov V. The role of lactobacilli in preventing urogenital and intestinal infections. Int. Dairy J. 1998;8:555-562
64. Reid G., Bruce A. W., Taylor M. Instillation of Lactobacillus and stimulation of indigenous organisms to prevent recurrence of urinary tract infections. Microecol. Ther. 1995;23:32-45
65.
Rossouw J. E., Burger E. M., van der Vyver P., Ferreira J. J. The effect of skim milk, yoghurt and full cream milk on human serum lipids. Am. J. Clin. Nutr. 1981;34:351-356
66. Rybka S., Fleet G. H. Populations of Lactobacillus delbrueckii ssp. bulgaricus, Streptococcus thermophilus, Lactobacillus acidophilus and Bifidobacterium species in Australian yoghurts. Food Aust. 1997;49:471-475
67. Sanders M. E., Huis in’t Veld J. Bringing a probiotic-containing functional food to the market: microbiological, product, regulatory and labeling issues. Antonie van Leeuwenhoek 1999;76:293-315[Medline]
68.
Savaiano D. A., El Anouar A. A., Smith D. E., Levitt M. D. Lactose malabsorption from yogurt, pasteurized yogurt, sweet acidophilus milk, and cultured milk in lactase-deficient individuals. Am. J. Clin. Nutr. 1984;40:1219-1223
69. Savaiano D. A., Kotz C. Recent advances in the management of lactose intolerance. Cont. Nutr. 1988;13:1-4
70. Sawada H., Furushiro M., Hirai K., Motoike M., Watanabe T., Yokokura T. Purification and characterization of an antihypertensive compound from Lactobacillus casei. Agric. Biol. Chem. 1990;54:3211-3219[Medline]
71. Shah N. Effectiveness of dairy products in alleviation of lactose intolerance. Food Aust 1993;45:268-271
72. Shalev E., Battino S., Weiner E., Colodner R., Keness Y. Ingestion of yogurt containing Lactobacillus acidopphilus compared with pasteurized yogurt as prophylaxis for recurrent candidal vaginitis and bacterial vaginosis. Arch. Fam. Med. 1996;5:593-596[Abstract]
73. Simenhoff M. L., Dunn S. R., Zollner G. P., Fitzpatrick M.E.D., Emery S. M., Sandine W. E., Ayres J. W. Biomodulation of the toxic and nutritional effects of small bowel bacterial overgrowth in end-stage kidney disease using freeze-dried Lactobacillus acidophilus. Miner. Electrolyte Metab. 1996;22:92-96[Medline]
74. Solis Pereyra B., Lemonnier D. Induction of human cytokines by bacteria used in dairy foods. Nutr. Res. 1993;13:1127-1140
75.
Spiegel C. A. Bacterial vaginosis. Clin. Microbiol. Rev. 1991;4:485-502
76. Stotzer P.-O., Blomberg L., Conway P. L., Henriksson A., Abrahamsson H. Probiotic treatment of small intestinal bacterial overgrowth by Lactobacillus fermentum KLD. Scand. J. Infect. Dis 1996;28:615-619[Medline]
77. Suarez F. L., Savaiano D. A., Levitt M. D. Review article: the treatment of lactose intolerance. Aliment. Pharmacol. Ther. 1995;9:589-597[Medline]
78. Sweet R. L. Role of bacterial vaginosis in pelvic inflammatory disease. Clin. Infect. Dis. 1995;20(suppl 2.):S271-S275
79. Tahri K., Grill J. P., Schneider F. Bifidobacteria strain behavior toward cholesterol: coprecipitation with bile salts and assimilation. Curr. Microbiol. 1996;33:187-193[Medline]
80. Takano T. Milk derived peptides and hypertension reduction. Int. Dairy J. 1998;8:375-381
81. Tannock G. W. Studies of the intestinal microflora: a prerequisite for the development of probiotics. Int. Dairy J. 1998;8:527-533
82. Tannock G. W. Probiotics: A Critical Review 1999 Horizon Scientific Press Wymondham, UK.
83. Taylor G.R.J., Williams C. M. Effects of probiotics and prebiotics on blood lipids. Br. J. Nutr. 1998;80:S225-S230[Medline]
84. Titze A, Kuhn C., Lorenz A., de Vrese M., Barth C. The influence of viable lactobacilli on lactose degradation in the gut of gnotobiotic animals. XIIth International Symposium on Gnotobiology, Honolulu, HI 1996;:43
85. Tomioka H., Saito H. Lactic acid bacteria in the support of immuno-compromised hosts. Wood B.J.B. eds. The Lactic Acid Bacteria: Vol. I The Lactic Acid Bacteria in Health and Disease 1992:263-296 Elsevier Applied Science London, UK.
86. van der Waaij D., de Vries J.M.B., Lekkerkerk van der Wees J.E.C. Colonization resistance of mice during systemic antibiotic treatments. J. Hyg. 1972;70:605-609
87.
van’t Veer P., Dekker J. M., Lamers J.W.J., Kok F. J., Schouten E. G., Brants H.A.M., Sturmans F., Hermus R.J.J. Consumption of fermented milk products and breast cancer: a case-control study in the Netherlands. Cancer Res 1989;49:4020-4023
88. Vesa T. H., Marteau Ph, Zidi S., Briet F., Pochart Ph, Rambaud J. C. Digestion and tolerance of lactose from yoghurt and different semi-solid fermented dairy products containing Lactobacillus acidophilus and bifidobacteria in lactose maldigesters–Is bacterial lactase important?. Eur. J. Clin. Nutr 1996;50:730-733[Medline]
89. Wheeler J. G., Shema S. J., Bogle M. L., Shirrell M. A., Burks A. W., Pittler A., Helm R. M. Immune and clinical impact of Lactobacillus acidophilus on asthma. Ann. Allergy Asthma Immunol. 1997;79:229-233[Medline]
90.
Wytock D. H., DiPalma J. A. All yogurts are not created equal. Am. J. Clin. Nutr. 1988;47:454-457
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