Sie sind auf Seite 1von 11


This Scientific Status A PUBLICATION OF

the scientific basis of

the hypothesis that

consumption of

probiotics can
P robiotics are defined as live microbial
food ingredients that have a beneficial
effect on human health (Salminen et al., 1998).
These include Bengmark (1998), Elmer et al.
(1999), Fonden et al. (1999), Holzapfel et al.
(1998), Lee et al. (1999), Naidu et al. (1999),
Salminen et al. (1996), Sanders (1998a), Sanders
and Huis in’t Veld (1999), and Tannock (1999a).
The concept of probiotics evolved at the turn of

positively influence the 20th century from a hypothesis first proposed

by Nobel Prize winning Russian scientist Elie Scientific Basis of Functionality
Hundreds of microbial species live in associa-
human health. Metchnikoff (Bibel, 1988), who suggested that tion with humans—on skin and in oral, intestinal
the long, healthy life of Bulgarian peasants and vaginal tracts. Bacterial populations have
Product and
been estimated to reach 100,000,000,000,000 cells
resulted from their consumption of fermented
at all sites of the human body (Tannock, 1994), a
regulatory issues are milk products. He believed that when consumed, number that is more amazing when considered in
the fermenting bacillus (Lactobacillus) posi- the context of exceeding by 10-fold the number of
also briefly
human cells associated with the human body.
tively influenced the microflora of the colon, Studies with germ-free (gnotobiotic) animals
decreasing toxic microbial activities. prove that microbial colonization is not required
The historical association of probiotics with for survival. In fact, microbial colonization can
fermented dairy products, still true today, stems have negative effects as a result of the toxic, geno-
from these early observations. Investigations in toxic, mutagenic, or carcinogenic potential of mi-
the probiotic field during the past several decades, crobial metabolites (Hill et al., 1971). Germ-free
however, have expanded beyond bacteria isolated animals, however, are more susceptible to infec-
from fermented dairy products to those of intesti- tion than conventional counterparts (Hentges,
nal origin. The probiotic bacteria most commonly 1992). The increased susceptibility to infection is
studied include members of the genera Lactobacil- attributed, at least in part, to poor immune func-
lus and Bifidobacterium. Saccharomyces boulardii, tion and the absence of “colonization resistance”
MARY ELLEN (McFarland et al., 1994), Escherichia coli (Kruis et (competition of normal microflora with invading
SANDERS al., 1997) and Enterococcus strains are used as pro- microorganisms; Vollaard and Clasener, 1994).
Author Sanders, a Professional biotics in non-food formats. Many probiotic Differences between conventional and germ-free
Member of IFT, is a Consultant strains have been identified, studied, and com- animals provide a basis for the belief that microbi-
with her company, Dairy and Food mercialized (Table 1). al colonization has important health implications
Culture Technologies, 7119 S. Probiotic-containing products are common in for host organisms.
Glencoe Ct., Littleton, CO 80122 Japan and Europe (Lee et al., 1999; Sanders and It is a big jump, however, from the assertion
and Research Professor, Dairy Huis in’t Veld, 1999). In the United States, probi- that colonizing microflora have a profound effect
otics are just now receiving attention by the food on normal human health to the probiotic hypoth-
Products Technology Center, Cali-
industry as healthful ingredients for an increas- esis that the addition of certain exogenous micro-
fornia Polytechnic State University,
ingly health-conscious consumer. The passage in organisms to the intestinal ecosystem will have a
San Luis Obispo, CA 93407 positive effect. The intestinal tract is a fairly stable
1994 of the Dietary Supplement Health and Edu-
cation Act invigorated the sale of probiotic prod- microbial ecosystem in the adult (Tannock, 1990).
ucts as dietary supplements. Acute perturbations as might result from antibiot-
This Scientific Status Summary provides an ic use, disease, or certain dietary changes seem to
overview of the current status of the proposed be self-correcting (Tannock, 1983). Probiotic bac-
mechanisms of activity of probiotics, their efficacy teria consumed even in high numbers do not be-
in humans, and some marketing and regulatory come permanent colonizers and are rarely detect-
considerations. Extensive reviews of these topics able in fecal or intestinal samples beyond a couple
may be consulted for additional information. of weeks after ingestion. This residence time likely



Probiotics dobacteria and enterococci. Although di-

rect comparisons of different strains are
rarely done, it appears that generaliza-
although hundreds of publications ad-
dress the topic. Mechanisms of action are
not thoroughly established; results for
tions about the probiotic performance of some endpoints are equivocal; results are
genera and species are difficult to make. spread among many different targets,
coincides with washout kinetics, extend- Until mechanisms are better understood population groups, endpoints, strains and
ed perhaps by some in situ replication of and controlled studies comparing doses; and properly controlled human in-
probiotics suited to the environment. isogenic strains differing in a well-de- tervention trials are limited. Yet the emer-
Therefore, it is necessary to consider that fined manner are completed, it is pru- gence of new public health risks, even in
probiotic effects may, in fact, be mediat- dent to assume that probiotic effects are industrialized nations, suggests ways in
ed by associations and mechanisms less strain-specific. In addition, physiological which effective probiotic bacteria may
intimate and more transient than those conditions of the host are likely to be as play an important role in maintaining hu-
of native microflora. important to probiotic efficacy as the man health.
Whether or not a specific probiotic microbial strain. Epidemiological and research evi-
bacterium will have beneficial, detrimen- dence suggests that intestinal mucosal im-
tal, or no effect on health cannot be pre- Justification of Use munity diminishes with age, leaving the
sumed strictly through determination of Are efforts to understand the role that elderly especially susceptible to infectious
its genus or species. The tempting specu- probiotic bacteria may play in human disease. This situation will continue to ex-
lation that the members of one genus or health justifiable, apart from interest in pand with the aging of the population.
species will consistently mediate specific yet another functional ingredient to lure Furthermore, some infections, once
effects is not supported by research. purchasing dollars from an increasingly thought benign and self-limiting or readi-
Strain-specific effects are frequently re- health-conscious consumer? Are benefits ly treatable with antibiotics, are now rec-
ported in a diversity of assays. Converse- from these bacteria going to make a sub- ognized as more serious health threats.
ly, for targets including immune func- stantive difference in the health of the av- For example, a diarrheal disease associat-
tion, anti-cancer effects, and anti-diar- erage consumer? At this point, the an- ed with antibiotic therapy is caused by an
rheal effects, similar positive effects have swers to these questions are speculative. opportunistic pathogen, Clostridium diffi-
been demonstrated for different strains The research characterizing the health ef- cile, carried asymptomatically by many.
of different genera, e.g., lactobacilli, bifi- fects of probiotic bacteria is not sufficient, This infection is generally treated success-
fully with a second antibiotic. Some infec-
Table 1 Characterized probiotic strains (partial list). Species identification tions, however, recur in spite of antibiotic
is as reported by the manufacturer and may not reflect the most current therapy. The association of this disease
with disruption of normal intestinal mi-
taxonomy (Yeung et al., 1999)
croflora during antibiotic treatment sug-
Strain Source gests the importance of finding alternative
Lactobacillus acidophilus NCFM® Rhodia, Inc. (Madison, Wis.) approaches to treatment.
L. acidophilus DDS-1 Nebraska Cultures, Inc. (Lincoln, Neb.) Campylobacter jejuni, believed to be
the leading cause of bacterial gastroen-
L. acidophilus SBT-2062a Snow Brand Milk Products Co., Ltd. (Tokyo, Japan)
teritis (Altekruse et al., 1999), can cause
L. acidophilus LA-1 Chr. Hansen, Inc. (Milwaukee, Wis.) Guillain-Barré syndrome (leading to
(same as strain LA-5 sold in Europe)
acute neuromuscular paralysis) in 0.1%
Lactobacillus casei Shirota Yakult (Tokyo, Japan) of cases of infection. Other potentially
L. casei Immunitas Danone (Paris, France) life threatening foodborne pathogens,
Lactobacillus fermentum RC-14 Urex Biotech (London, Ontario, Canada) e.g., enterohemorrhagic Escherichia coli
strains (Buchanan and Doyle, 1997),
Lactobacillus johnsonii La1 (same as Lj1) Nestlé (Lausanne, Switzerland)
have emerged. Multiple antibiotic resis-
Lactobacillus paracasei CRL 431 Chr. Hansen, Inc. (Milwaukee, Wis.) tance is a continual threat in the battle
Lactobacillus plantarum 299V Probi AB (Lund, Sweden) against once-treatable infections, with
Lactobacillus reuteri SD2112 (same as MM2) Biogaia (Raleigh, N.C.) vancomycin-resistant enterococci and
Lactobacillus rhamnosus GG a
Valio Dairy (Helsinki, Finland) methicillin-resistant Staphylococcus au-
reus serious concerns, especially in hos-
L. rhamnosus GR-1 Urex Biotech (London, Ontario, Canada)
pital environments. And in non-indus-
L. rhamnosus 271 Probi AB (Lund, Sweden) trialized nations, infections such as ro-
L. rhamnosus LB21 Essum AB (Umeå, Sweden) tavirus claim the lives of hundreds of
Lactobacillus salivarius UCC118 University College (Cork, Ireland) thousands of infants yearly (Parashar et
al., 1998). For these reasons, a safe, cost-
Lactobacillus lactis L1A Essum AB (Umeå , Sweden)
effective, “natural” barrier to microbial
Bifidobacterium lactis Bb-12 Chr. Hansen, Inc. (Milwaukee, Wis.) infection or to the negative effects of in-
Bifidobacterium longum BB536a Morinaga Milk Industry Co., Ltd. (Zama-City, Japan) digenous microorganisms may be signif-
B. longum SBT-2928a Snow Brand Milk Products Co., Ltd. (Tokyo, Japan) icant to human health.
Bifidobacterium breve strain Yakult Yakult (Tokyo, Japan)
Effects on Human Health
Strains have been awarded Foods for Specified Health Use status in Japan Research suggests that probiotic bac-



teria may mediate a variety of health ef- physiology. Probiotics have ameliorated one year) increased the recurrence-free
fects through numerous proposed mech- acute toxic effects of gut flora metabo- period among human subjects with su-
anisms (Table 2). Some blinded, ran- lism in clinical systems, such as small perficial bladder cancer (Aso and Aka-
domized, placebo-controlled studies bowel bacterial overgrowth (Simenhoff zan, 1992). Additional population stud-
conducted with a meaningful number of et al., 1996) and liver disease (Nanji et ies and human intervention trials are
human subjects have yielded sufficiently al., 1994; Read et al., 1966). A brief as- needed to confirm this type of effect.
positive results (Aso and Akazan, 1992; sessment of probiotic effects targeted to- Such studies can be justified by the posi-
Belloma et al., 1980; Gade and Thorn, ward several endpoints, with emphasis tive results seen to date from studies us-
1989; McFarland et al., 1994; Saavedra et on results from human studies, where ing a variety of biomarkers and the plau-
al., 1994) to justify further investigation possible, follows. sibility of proposed mechanisms.
of the probiotic hypothesis. Alleviation • Cancer. Research has demonstrated Results suggest that probiotic bacte-
of lactose intolerance symptoms and that dietary components may increase or ria appear able to counteract mutagenic
anti-diarrheal effects are the best sub- decrease cancer incidence (Williams and and genotoxic effects in the colon and
stantiated effects. Anti-cancer and im- Wynder, 1996). Evidence that probiotic other organ sites. Additionally, mecha-
mune modulation effects are encourag- bacteria may be a dietary constituent nistic studies suggest that probiotic bac-
ing, but need more thorough substantia- that reduces cancer risk (Table 3) is de- teria or their byproducts influence epi-
tion in humans. Modulation of the gut rived from several lines of evidence thelial cell kinetics in the colon, decreas-
microflora (populations and activities) (Hirayama and Rafter, 1999; Mital and ing cancer cell proliferation. What can-
and influence on mucosal immunity are Garg, 1995; Rafter, 1995). One study not be determined from scientific evi-
mechanisms of probiotic function with demonstrated that a powder preparation dence to date is to what extent regular
potential to broadly influence human of L. casei (1010 CFU three times/day for probiotic consumption might influence
cancer in humans. In addition, the cu-
Table 2 Potential and established effects of probiotic bacteria (adapted mulative evidence involves many differ-
from Sanders and Huis in’t Veld, 1999) ent probiotic strains, feeding levels, ex-
posure times, target cancer sites, and
Target Health Benefit Postulated Mechanism study methods. Therefore, precise trans-
Aid in lactose digestion Bacterial lactase hydrolyses lactose lation of these results into specific rec-
Resistance to enteric Secretory immune effect ommendations is difficult.
pathogens Colonization resistance • Intestinal Tract Function. Gas-
Alteration of intestinal conditions to be less favorable for pathogenicity trointestinal disturbances can range
(pH, short chain fatty acids, bacteriocins) from annoying to life-threatening. Diar-
Alteration of toxin binding sites
Influence on gut flora populations
rheal illnesses have a host of microbio-
Adherence to intestinal mucosa, interfering with pathogen logical, immunological and physiological
adherence causes, some related to the disruption of
Upregulation of intestinal mucin production, interfering with pathogen normal microecology. Improper func-
attachment to intestinal epithelial cells tion of the immune system that is related
Anti-colon cancer effect Mutagen binding to decreased tolerance to indigenous mi-
Carcinogen deactivation croflora can lead to immunopathogene-
Inhibition of carcinogen-producing enzymes of colonic microbes sis in chronic inflammatory bowel dis-
Immune response ease (Merger and Croitoru, 1998), which
Influence on secondary bile salt concentration
can be refractory to conventional treat-
Small bowel bacterial Influence on activity of overgrowth flora, decreasing toxic ment. Underlying pathology (e.g., chron-
overgrowth metabolite production ic kidney failure) and achlorhydria
Alteration of intestinal conditions to be less favorable to overgrowth
flora activities or populations (brought on by aging) can result in bac-
terial overgrowth of the small bowel and
Immune system modulation Strengthening of non-specific defense against infection and tumors
lead to abnormal and harmful microbial
Adjuvant effect in antigen-specific immune responses
Enhancement of secretory IgA production activities (Nanji et al., 1994; Simenhoff et
al., 1996). Disruptions in intestinal per-
Allergy Prevention of antigen translocation into blood stream
meability barriers can lead to transloca-
Blood lipids, heart disease Assimilation of cholesterol within bacterial cell tion of bacteria into the blood stream
Increased excretion of bile salts due to deconjugation by bile salt (Wells et al., 1988). Consumption of
Antioxidative effect non-digestible foodstuffs (e.g., lactose
for lactose intolerant people, soluble fi-
Antihypertensive effect Peptidase action on milk protein yields tripeptides which inhibit
bers) can provide fermentable substrates
angiotensin 1 converting enzyme
Cell wall components act as angiotensin converting enzyme inhibitors for growth of intestinal microbes, some-
times with deleterious effects.
Urogenital infections Adhesion to urinary and vaginal tract cells
Colonization resistance
Probiotic bacteria have been shown
Inhibitor production (H2O2, biosurfactants) to improve the clinical outcome in many
intestinal disease targets (Table 4; Elmer
Infection caused by Production of inhibitors of H. pylori (lactic acid and others)
Helicobacter pylori et al., 1996; Salminen et al., 1998a). Most
convincing are the blinded, placebo-con-
Hepatic encephalopathy Inhibition of urease-producing gut flora
trolled trials with human subjects (Bello-



Probiotics logic activity can lead to serious health

problems; the suffering brought on by
allergic and inflammatory reactions is a
largest body area interacting with the en-
vironment. The gut-associated lymphoid
tissue (GALT) transforms the gas-
testimony to these occurrences. Im- trointestinal tract into the largest im-
mune function can be compromised in mune organ in the human body. Ap-
ma et al., 1980; Gade and Thorn, 1989; the elderly and in those on immuno- proximately 1010 immunoglobulin-pro-
McFarland et al., 1994; Saavedra et al., suppressing medications and suffering ducing cells per meter of small bowel are
1994). Although the clinical protocols fre- from certain diseases. The role of func- estimated to be present, accounting for
quently fall short of the double-blinded, tional foods, directed for the most part approximately 80% of all immunoglob-
placebo-controlled ideal, the scientific evi- toward a healthy population with com- ulin-producing cells in the body (Targan
dence suggests that probiotic bacteria, petent immune function, is not clear. and Shanahan, 1994). Subsequently, the
consumed at high levels (109-1011/day), However, it is an area of much active intestinal tract can evoke a variety of im-
can decrease the incidence, duration, and research, consumer interest, and prod- munological responses from many dif-
severity of some intestinal illnesses. uct positioning. ferent local immune cells (McCracken
• Immune Function. Exposure to for- The oro-gastro-intestinal system is and Gaskins, 1999). It is through this
eign antigens elicits a complex cascade of a prime means of interface between mechanism that probiotic bacteria are
responses from the human body, includ- foreign antigens, (either pathogens, postulated to influence the immune re-
ing launching protective reactions against harmless bacteria, or food antigens) sponse, although genera in addition to
pathogens and suppressing activity against and mucosal surfaces. The total mucos- Lactobacillus and Bifidobacterium have
food antigens and colonizing microflora. al surface area of the adult human gas- been evaluated as immune stimulators or
Improperly directed or balanced immuno- trointestinal tract is up to 300 m2, the “biological response modifiers” with
varying degrees of success. The influence
Table 3 Activities of probiotics or probiotic-containing products of probiotic bacteria on the immune re-
that may play a role in reducing risk of cancer sponse has been thoroughly reviewed by
Activity Suppressed Reference Marteau and Rambaud (1993), Mc-
Cracken and Gaskins (1999), Perdigón
Cell growth and differentiation of tissue culture cells Baricault et al., 1995 and Alvarez (1992), and Perdigón et al.
Aberrant crypt foci in colonic tissue of animals Rowland et al., 1998; Rao et al., 1999. (1995).
Tumors in mice (colon, liver, mammary) Reddy and Rivenson, 1993; Goldin et al., 1996; Many studies using in vitro assess-
Adachi, 1992. ments of immune response or non-oral
Recurrence of superficial bladder cancer in humans Aso and Akazan, 1992 routes of probiotic introduction have
Enzyme activities (nitroreductase, b-glucuronidase, Ling et al., 1994;
questionable relevance. Animal models
azoreductase, 7-a-dehydroxylase, glycocholic acid McConnell and Tannock, 1993; and human studies (Table 5) provide a
hydrolase) involved in conversion of procarcinogens Goldin et al., 1980 baseline understanding of the degree and
into carcinogens in feces of laboratory animals and type of probiotic-induced immune re-
humans; not all parameters positively influenced in all studies. sponse. From these studies, it appears
Mutagenic activity Renner and Munzner, 1991 that probiotic bacteria are able to en-
Genotoxicity Venturi et al., 1997 hance both non-specific and specific im-
mune responses by activating macroph-
ages; increasing levels of cytokines; in-
Table 4 Targets and postulated mechanisms of probiotic influence on creasing natural killer cell activity; and
abnormal gastrointestinal conditions. Many studies were designed as increasing levels of immunoglobulins,
pilot studies (small numbers of subjects, not blinded) and results have especially secretory IgA. Viable probiotic
cells, dead cells, or fermentation prod-
not been confirmed in large trials
ucts have been shown to mediate im-
Intestinal Conditions Mediated by Probiotic Bacteria Reference mune activity. Important in this capabil-
Antibiotic-associated diarrhea Orrhage et al., 1994 ity is the positive influence of probiotics
Toxic amines in blood stream of chronic kidney and liver disease Muting et al., 1968 on immune activity without eliciting a
patients with small bowel bacterial overgrowth Simenhoff et al., 1996 harmful inflammatory response.
Inflammatory bowel diseases Kruis et al., 1997 Biological effects correlated with en-
hanced immune function, such as pro-
Lactose intolerance symptoms Suarez et al., 1995
tection against viral and bacterial patho-
Rotavirus or other pediatric diarrhea Belloma et al. 1980 gens and tumor inhibition, have also
Majamaa et al., 1995
been measured (Marteau and Rambaud,
Saavedra, et al., 1994
Vanderhoof and Young, 1998 1993). This effort is important because it
provides a physiologically relevant mea-
Intestinal permeability to antigens (rats) Isolauri et al., 1993a, b
sure of functionality. It is difficult to in-
Travellers’ diarrhea Oksanen et al., 1990 terpret statistically significant results in
Irritable bowel syndrome Gade and Thorn, 1989 immune function studies in terms of
Neutralization of cholera toxin (rats) Dias et al., 1995 what degree of influence these changes
would be expected to have on human
Clostridium difficile pseudomembranous colitis Rolfe, 1995
health. Importantly, long-term studies



have not established whether the im- In one study, changes in receptors viduals (Trapp et al., 1993). A significant
mune response to exogenous probiotic mediating phagocytosis was measured in decrease in allergy symptoms was ob-
strains is a temporary response upon ex- eight milk-hypersensitive (not lactose in- served in individuals consuming yogurt
posure to a foreign strain or one that tolerant) adults consuming milk and containing live, active bacteria compared
would continue to be expressed after ex- milk with Lactobacillus GG (Pelto et al., to individuals consuming pasteurized
tended feeding (Tannock, 1999b). 1996). Consumption of the probiotic- yogurt and those who did not consume
• Allergy. Preliminary research on containing milk did not result in a sig- yogurt. No microbiological characteriza-
probiotic-mediated modulation of cer- nificant increase in receptor expression tion of the yogurt was reported. Another
tain allergic reactions has been reported. whereas consumption of regular milk report, however, did not show clinical
A breakdown of the intestine’s mucosal did, suggesting that this strain may sup- improvement in 15 asthmatic subjects
barrier function, allowing extensive anti- press a milk-induced immune inflam- fed yogurt and yogurt with L. acidophilus
gen challenge, may be a factor in some matory response. Unfortunately, symp- in a crossover design study (Wheeler et
allergic reactions. Since probiotic bacte- toms were not evaluated. al., 1997). Further study of the role of
ria have been shown to improve mucosal Symptoms were evaluated, however, probiotics in allergic response is neces-
barrier function, the hypothesis that they in a partially blinded 12-month study in sary.
may play a role in moderating allergic which yogurt and pasteurized yogurt • Stomach Health. The ability of
response was tested. were fed to college-age and elderly indi- probiotic bacteria to influence coloniza-
tion and activity of Helicobacter pylori,
which is associated with chronic gastri-
Table 5 Immune effects evoked by probiotic bacteria or yogurt in immu- tis, peptic ulcers, and risk for gastric can-
nocompetent humans cer (Marshall, 1994), has been evaluated.
Test product Effect Reference Conventionally colonized (stomach mi-
croflora is dominated by lactobacilli)

Fermented milk (ST) with phagocytic activity + respiratory Donnet-Hughes et al., 1999
Lactobacillus johnsonii La1 (108/d burst of peripheral blood leukocytes mice resisted infection by H. pylori,
or 109/d) no effect seen at 108/d whereas germ-free mice did not (Kabir
et al., 1997). Results from animal (Aiba

Yogurt (1011 each ST with LB/d) 2’-5’ A synthetase activity in BMC Solis-Pereyra et al., 1997
(control: milk) (as more stable indicator of IFN) in et al., 1998; Kabir et al., 1997) and hu-
yogurt group; no effect on IFN-g, man (Michetti et al., 1999) studies sug-
IL-1b, or TNF-a gest that some probiotic bacteria or their

Lactobacillus GG capsules (dose serum IgA response to Salmonella Jung, 1999 end-products may inhibit H. pylori in-
not specified); placebo: sucrose typhi lipopolysaccharide vaccine fection.
(adjuvant effect) The ability of Lactobacillus salivarius

Lactobacillus GG powder IgM secreting cells against Isolauri et al., 1995 WB1004 to inhibit H. pylori colonization
capsules (5 x 1010); placebo: rotavirus vaccine of human or murine gastric epithelial
microcrystalline cellulose cells in vitro was extended in vivo in gno-
Fermented milk (1011/d No effect on natural killer cell Spanhaak et al., 1998 tobiotic mice (Kabir et al., 1997). Inter-
Lactobacillus casei Shirota) activity, phagocytosis or cytokine estingly, complementary studies indicat-
(control: milk) production ed that neither S. aureus nor Enterococcus
Fermented milk with L. johnsonii No effect on lymphocyte subsets, Schiffrin et al., 1995 faecalis afforded the same protection

La1 (7 x 1010) or Bifidobacterium but phagocytosis of Escherichia coli from H. pylori infection. Colonization by
bifidum Bb12 (1010); no placebo compared to pre-feeding levels H. pylori was also reduced by feeding L.

Lactobacillus brevis subsp. a-IFN (as measured by 2’-5’ Kishi et al., 1996 salivarius after infection with H. pylori.
coagulans (Labre) tablet, live, and A synthetase activity) in 3 and Aiba et al. (1998) found that L. salivari-
heat-killed, 1.5, 3, and 6 x 108/d 6 x 108/d test groups us, but not L. casei or L. acidophilus, in-

Yogurt (1011 each ST + LB/d) 2’-5’ A synthetase activity in BMC Solis-Pereyra and hibited H. pylori colonization in a mouse
(control: milk) Lemonnier, 1993 model. Lactic acid production was

Fermented milk with 4 x 109-10/d serum IgA response to Salmonella Link-Amster et al., 1994 thought to correlate with inhibition.
L. johnsoni La1 and Bifidobacterium; typhi vaccine (adjuvant effect) Lactic acid was shown to be more inhibi-
control: diet with no fermented tory to H. pylori in vitro than acetic or
foods hydrochloric acids (Midolo et al., 1995).

Yogurt with 3 x 1012/d ST and LB serum IFN-g, B lymphocytes and De Simone et al., 1993 Michetti et al. (1999) administered
NK cell subset to humans in a double-blind, controlled

Lactobacillus GG (2 x 1010-11) rotavirus specific IgA antibody Kaila et al., 1992, 1995 clinical study a whey protein-based fer-
secreting cells in rotavirus-infected mentation product supernatant fluid
infants prepared by growth of L. johnsonii La1.

2x1010 CFU/day dried IgA secreting cells; no change Malin et al., 1996 They assessed effects using a carbon-13-
Lactobacillus GG in clinical status of Crohn’s disease urea breath test, endoscopy, and stomach
patients. biopsy. Reductions in 13CO2 in the 13C-

Bifidobacterium lactis formula IgA Fukushima et al., 1998 urea breath test were observed in sub-
ST, Streptococcus thermophilus; LB, Lactobacillus delbrueckii subsp. bulgaricus; LA, Lactobacillus jects consuming the probiotic product,
acidophilus; B, Bifidobacterium spp.; IFN, interferon; IL, interleukin; TNF, tumor necrosis factor; Ig, suggesting an inhibition of infection; the
immunoglobulin; BMC, blood mononuclear cells inhibition extended four weeks after ces-



Probiotics tion, with potential implications for se-

rum cholesterol levels (Eyssen, 1973).
Studies of the effects of culture-contain-
jugated bile acids escaping re-entry into
the hepatic circulation enter the colon
where they can be converted into sec-
C O N T I N U E D ing dairy products or probiotic bacteria ondary bile acids by colonic microbes.
on cholesterol levels has yielded equivo- Secondary bile acids are known cancer
cal results (Taylor and Williams, 1998). promoters; hence, this activity could re-
sation of treatment. Gastric biopsies, Since 1974, 15 published studies have sult in a health risk. A potential increased
however, indicated that H. pylori coloni- evaluated blood lipids in human subjects risk of colon cancer may outweigh any
zation persisted. In vitro studies suggest- consuming fermented milk products, benefit of reduction of serum cholesterol
ed that inhibition resulted from more with a total of 534 subjects. Statistically levels. These hypotheses have not been
than lactic acid, and was strain-specific. significant lowering of cholesterol confirmed in animal or human studies,
These results suggest that probiotic bac- ranged from 2.4 – 23.2% for total cho- although Gilliland et al. (1985) estab-
teria and their metabolic end-products lesterol and 9 – 9.8% for low-density li- lished a cholesterol-lowering effect of a
can inhibit H. pylori and its physiological poprotein cholesterol. The studies have cholesterol-assimilating (but not a non-
effects. Results regarding the influence of been criticized for failure to stabilize assimilating) strain in boars. Further re-
probiotics on H. pylori infection must be baselines prior to onset of the feeding search on any mechanisms should be
extended and confirmed. protocol, small sample size, short study preceded by evidence for clinical effect in
• Urogenital Health. Similar to the duration, unreasonably large fermented at least one thorough, long-term human
intestinal tract, the urogenital tract in milk intake requirements, small differ- study.
women is highly colonized and suscepti- ences, and failure to control for diet and • Hypertension. Dietary recommen-
ble to infection upon colonization dis- physical activity of subjects. In the stud- dations accompany more aggressive
ruption (Reid et al., 1998). Both urinary ies showing statistically significant re- strategies to control hypertension, and
and genital tract infections have been sults on the lowering of either total cho- some preliminary evidence suggests that
linked to bacteria originating from the lesterol or low-density lipids, the treat- food products derived from probiotic
colon. This has led to the hypothesis that ment duration was six weeks or less. Fur- bacteria could possibly contribute to
modulation of gut microflora through thermore, one report showed increases blood pressure control (Takano, 1998).
consumption of bacteria can have an ef- in both total cholesterol and low-density This antihypertensive effect has been
fect on urogenital ecosystems (Sobel, lipoprotein (Rossouw et al., 1981) and documented with studies in spontaneous
1999). Populating the colon with lacto- another showed decreases in high-densi- hypertensive rats (Nakamura et al., 1995;
bacilli enables the colon to serve as a ty lipoprotein (Anderson and Gilliland, 1996) and one human clinical study
source of beneficial, not just harmful, 1999). (Hata et al., 1996). Two tripeptides, va-
bacteria. The effect of probiotic bacteria on line-proline-proline and isoleucine-pro-
Several studies have correlated vagi- reduction of serum cholesterol and line-proline, isolated from fermentation
nal health (absence of infections) with mechanisms of any effects are unknown. of a milk-based medium by Saccharomy-
the presence of lactobacilli, and specifi- One hypothesis suggests that some ces cereviseae and Lactobacillus helveticus
cally hydrogen peroxide-producing lac- strains of L. acidophilus can assimilate have been identified as the active compo-
tobacilli (Hillier et al., 1992). Some clini- the cholesterol molecule (Gilliland et al., nents. These tripeptides function as an-
cal substantiation of the ability of probi- 1985); this activity has been reported in giotensin-I-converting enzyme inhibitors
otics to decrease recurrence of urogenital in vitro assays (Gilliland et al., 1985; Ra- and reduce blood pressure. Based on this
infections in women exits (Bruce and sic et al., 1992). However, some have technology, Calpis (Kanagawa, Japan)
Reid, 1988; Hallen et al., 1992; Hilton et questioned the physiological relevance of developed a pasteurized product
al., 1992; Reid et al., 1995; Shalev et al., binding or assimilation observed in an in (Ameal-S) having Foods for Specified
1996). Most of these studies were con- vitro, aqueous assay conducted at pH 6.0 Health Use (FOSHU) status. Unlike
ducted with intravaginal instillations of or lower. It has been suggested that pH- many other probiotic-induced effects, it
probiotic bacteria. Oral consumption of dependent, transient cholesterol precipi- is important to note that this effect is
certain probiotic-containing products, tation in laboratory media were misin- mediated by a fermentation end-prod-
however, was found to mediate decreased terpreted as assimilation (Klaver and uct, not viable probiotic cells.
recurrence of Candida infections and Meer, 1993; Tahri et al., 1996). Another antihypertensive activity
bacterial vaginosis (Hilton et al., 1992; The ability of certain probiotic lacto- was associated with cell wall fragments
Shalev et al., 1996). To confirm a role of bacilli and bifidobacteria to enzymatical- of Lactobacillus casei YIT9018 (Sawada et
dietary sources of probiotic bacteria in ly deconjugate bile acids has also been al., 1990). Tested in a placebo-controlled
the prevention of urogenital infections, suggested to have a role in regulating trial with 28 human hypertensive sub-
placebo-controlled, blinded studies us- cholesterol levels in humans. Deconju- jects, powdered cell extracts (not viable
ing oral routes of introduction with suf- gated bile acids are more efficiently ex- cells) were administered orally and ef-
ficiently large study groups are needed. creted (De Smet et al., 1994). Because fects on systolic pressure, diastolic pres-
• Cholesterol. Elevated levels of cer- cholesterol is a precursor of bile acids, sure, and heart rate were determined.
tain blood lipids are a risk factor for car- this could lead to reduction of serum Small, but statistically significant, de-
diovascular disease. The observation that cholesterol as cholesterol molecules are creases in all three measurements were
conventional animals excrete higher lev- converted to bile acids to replace those noted. These results suggest that probiot-
els of cholesterol in feces than germ-free lost through excretion. The desirability ic bacteria or their fermentation end-
animals suggests that colonizing mi- of bile salt hydrolysis as a probiotic at- products may be effective in mediating a
crobes may influence cholesterol excre- tribute, however, is questionable. Decon- mild antihypertensive effect. Confirma-



tion in long-term, placebo-controlled However, isolated reports of associa- probiotic concept are exhibited with the
human subjects is needed. tion of lactobacilli (Aguirre and Collins, marketing of Lactobacillus GG as a di-
• Other Health Effects. Probiotic in- 1993; Saxelin et al., 1996) and bifidobac- etary supplement (Culturelleâ) by ConA-
fluence on a variety of other clinical tar- teria (Gasser, 1994) with human infec- gra (Omaha, Neb.), the entry of Dannon
gets has been evaluated. Probiotic-medi- tion (commonly endocarditis) in pa- (Tarrytown, N.Y.) into the dairy bever-
ated reduction in the severity of reaction tients with compromised health suggest age market with Actimel (labeled as a di-
to exposure to radioactive isotopes has that these microbes may have some op- etary supplement, containing yogurt cul-
been shown in mice (Dong et al., 1987) portunistic capability. Safety concerns tures and L. casei), and the addition by
and humans (Henriksson et al., 1995; were expressed regarding the use of en- Stonyfield Farms (Londonderry, N.H.)
Korschunov et al., 1996; Salminen et al., terococci as probiotic microbes (Adams of four probiotics (L. casei, Bifidobacteri-
1988). The effects of endotoxemia asso- and Marteau,1995). The association of um, L. acidophilus and L. reuteri) to all of
ciated with alcoholic liver disease were Enterococcus faecium and Enterococcus its yogurt products. The approach taken
reduced by probiotics (Nanji et al., faecalis with bacteremia and the in- by Dannon is unique with U.S. foods be-
1994). Probiotics have been used in en- creased incidence of antibiotic resistance cause it uses (and claims on the label)
teral feeding to provide nutritional sup- in these strains provide rationale for ex- very high populations of viable probiotic
port of surgery patients (Bengmark and cluding them from food formulations (1010 L. casei/serving). The outer wrap on
Gianotti, 1996). (Lai, 1996). Enterococci, however, are as- the package of four 100-ml bottles reads
In addition to proposed direct effects sociated with some traditional food fer- “Helps fortify your body’s natural de-
on humans, probiotics may also have im- mentations (Giraffa et al., 1997) and are fenses.” This product does not, however,
plications for human health through currently used in some dietary supple- identify the specific strain of L. casei
their use in animal agriculture. Probiot- ment formulations. used. Because many dietary supplement
ics have been tested for prevention of In general, health-related statements products are formulated with strains
food animal colonization with patho- have not been used in the United States with no proven clinical efficacy, strain
gens. Probiotics may also benefit animal on the labels of probiotic-containing identification is useful to identify re-
agriculture through greater resistance of food products (Sanders, 1998b). Incon- sponsibly formulated products.
farm animals to infectious diseases, in- spicuous mention of genus and probiotic Opportunity exists for food manu-
creased growth rate, improved feed con- species contained in the food is com- facturers to formulate a new generation
version, and increased yield of milk and mon, although this taxonomic informa- of probiotic-containing products. Such
eggs (Fuller, 1998). Commercial probiot- tion is not always accurate (Yeung et al., an endeavor should consider:
ic products for use in animal agriculture 1999). Although structure/function • Choice of strain or strain combina-
are available. statements about gastrointestinal tract tions. This should be based on evalua-
health, immune function, or improved tions of health effects, mechanisms of ac-
U.S. Regulatory Issues and digestion are used in the labeling of pro- tion, and stability characteristics of the
Safety biotic dietary supplements, most food specific strain using validated biomark-
Several of the bacteria used in the manufacturers avoid them. Manufactur- ers in in vitro, animal, and human sub-
United States as probiotics are listed by ers avoid them although structure/func- ject studies.
the Food and Drug Administration tion claims appear to be allowable on • Definition of a physiologically rele-
(FDA) on its “Partial List of Microorgan- foods (with no requirement for the FDA vant (dose which research suggests pro-
isms and Microbial-Derived Ingredients disclaimer statement —that the claim vides a beneficial health effect or reduced
that are Used in Foods” (http:// has not been evaluated by FDA—or 30- risk of disease) consumption levels. The usual ap- day postmarket notification of FDA as • Definition of the active principle of
proach for safety assessment for market- required for supplements; McNamara, the probiotic product. Non-viable cells,
ing probiotic bacteria in the United 1998). This caution may stem from food fermentation end-products, and en-
States is presumption of safety, reasoned industry concern with the body of scien- zymes have been shown to mediate pro-
by a long history of safe use in fermented tific substantiation of probiotic effects biotic effects (Ouwehand and Salminen,
dairy products. and whether it meets the “truthful and 1998). In recognition of this fact, a defi-
The safety of lactobacilli and bifido- not misleading” requirement of the FDA nition of probiotics was recently pro-
bacteria has been recently reviewed for structure/function statements. posed (Salminen et al., 1999), which ex-
(Salminen and von Wright, 1998). The tends the definition beyond only viable
general conclusion is that the pathogenic Product Issues cells to include “components of microbi-
potential of lactobacilli and bifidobacteria The current market in the United al cells.” A clear understanding of the ac-
is quite low. This conclusion is based on States for probiotics is difficult to assess tive component of a probiotic product is
the widespread consumption of these mi- (Sanders, 1998b). It is an undeveloped essential to development of appropriate
croorganisms in fermented foods, their market, if trends in Japan and Europe quality control measures as well.
Pathogen Temperature
presence as normal colonizers in the hu-Time toare
indication. Yogurt manufacturers • Consumer communication pro-
°C °F formation (h)
man body, failure to isolate these bacteria in the U.S. have added L. acidophilus, and gram that discusses the basis of probiotic
as primary pathogens, and lack of nega- in some cases Bifidobacterium species, to functionality and specifics of the probi-
tive side effects of the bacteria when fed in their products for years, and unferment- otic product.
high levels to immunocompromised hu- ed fluid milk containing probiotic bacte- • Package labeling to communicate
mans (premature infants, elderly, AIDS ria comprises a small niche market. approximate numbers of viable cells at
patients, Chron’s disease patients, and Some recent moves by U.S. food compa- the end of shelf life, and the genus, spe-
people with enteric infections). nies toward a warmer embrace of the cies, and strain used. Use of a strain desig-



Probiotics nologies to track the influences of probi-

otic consumption on gut microecology is
another exciting area of research (Kitts,
probiotics provide not only viable bac-
teria, but also high-quality macronutri-
ents and unique micronutrients (such
C O N T I N U E D 1999). Dynamic models of the stomach, as calcium, fermentation end-products,
small intestine, and colon to simulate the bioactive peptides, sphingolipids, and
in-vivo gastrointestinal environment conjugated linoleic acids) found in fer-
nation on package labeling communicates have been developed (Marteau et al., mented milk products (McBean, 1998;
the importance of strain specificity in 1997; Minekus et al., 1995) and may pro- 1999; Van der Meer et al., 1998). At the
probiotic effects, clearly links the specific vide an important link between conven- same time, the natural buffering of
strain used to published studies, and pro- tional in-vitro methods and in-vivo clini- stomach acid by the food carrier would
vides a measure of protection against con- cal studies. Advances in the understand- enhance stability of the probiotic after
fusion if taxonomic developments alter ing of genetic transfer systems and gene consumption. Formulation of food
the species to which a specific strain is as- regulation of the lactobacilli (Klaenham- products with additional vitamins,
signed. A strain remains the same regard- mer, 1995) have enabled the construc- non-digestible carbohydrates, soluble
less of changeable taxonomic placements. tion of isogenic strains of lactobacilli fiber, phytochemicals, or other bioac-
• Package labeling to communicate that can be applied to animal or human tive ingredients could further enhance
product health benefits. No approved feeding studies to determine which the dietary value of the product.
health claim exists for probiotic bacteria strain attributes are essential for probiot-
and any health statements, such as struc- ic effects. The use of a Lactobacillus-free Conclusions
ture/function statements, must comply mouse colony could be quite useful for Studies documenting probiotic ef-
with FDA regulations (McNamara, 1998; such controlled studies (Tannock et al., fects in humans are limited, although
Sanders and Huis in’t Veld, 1999). 1988). Increased clinical evaluation is results in several biological systems are
• Compatibility of probiotic with paramount, and will be most likely to intriguing. The degree of evidence re-
food format. Probiotic survival in foods succeed if well-defined probiotic bacteria quired to substantiate bioactivity of
is an important consideration in this re- are used in established clinical systems. food ingredients is not clearly estab-
gard. Factors involved in probiotic sur- The benefit of probiotics as healthful lished. This is a complex issue involving
vival are complex—involving strain ge- ingredients could be enhanced if used in both regulatory and scientific consider-
netics, strain cultivation procedures, combination with other health-promot- ations. The commercial use of probiot-
preservation method, preservation com- ing dietary strategies. In the United ics, however, has proceeded because es-
pounds, food composition, storage tem- States, the growth of the probiotics mar- sentially no risk is associated with con-
perature, and storage time, among oth- ket is occurring mostly in the dietary sumption of well-defined probiotics in
ers. In general, probiotic survival benefits supplement arena. Whole foods, howev- foods and many benefits are possible.
from storage at refrigeration tempera- er, represent a very attractive vehicle for Perhaps the most compelling evidence
tures, a fact sometimes ignored in the delivery of probiotics, although delivery for probiotic efficacy is in the areas of
storage of dried probiotic preparations. through a traditional dietary supplement anti-diarrheal effects and improved di-
The requirement for refrigerated storage is convenient for some (especially clini- gestion of lactose in lactose-intolerant
of fermented dairy products encourages cal) applications. Probiotic bacteria have people, because these findings have
probiotic survival. always had a natural association with been substantiated in human studies
dairy foods. Dairy products containing and in more than one laboratory. These
Considerations for the Future
The increased worldwide interest in
Table 6 Future research in the probiotics area
probiotics has set the stage for expanded
marketing of these products, even Determine the physiological role, mechanisms of action, and extent of influence of probiotics in
though much research remains to be human health using human feeding studies. Studies on high-risk human populations for colon cancer
done. Some research goals are shown in or cancer recurrence would be a possible target for some studies.
Table 6. Broadened clinical evaluation in Validate biomarkers used for assessing probiotic function. Testing of predictions based on biomarker
both healthy and diseased human popu- studies with actual results in human clinical evaluations is needed. Biomarker validation in the areas
lations will do much to increase under- of immune system, cancer, and gut microecology is especially important. Once validated, biomarkers
will be useful tools to assess dose-dependence and strain-specific responses. Biomarkers commonly
standing of important aspects of probi- used to select strains for probiotic use (adherence in tissue cultures, cholesterol assimilation,
otic bioactivity, including strain specific- competitive exclusion of pathogens in tissue culture, inhibitor [bacteriocins, organic acids] production,
ity, dose requirements and extent of clin- lactase activity) have never been tested in controlled studies to determine if mutants without the
ical efficacy. One exciting area of current characteristic perform any differently in clinical evaluations.·
research is chromosome sequencing of Assess effects of probiotics on populations and activity of gut microbes. The application of gene-
probiotic Lactobacillus species, including based methods holds much promise in this field.
L. johnsonii La1 (Zink, 1999) and L. aci- Determine the role of probiotics as part of a whole food compared to isolated component.
dophilus (Cano and Willoughby, 1999;
Improve reliability and ease of taxonomic classification of probiotic bacteria. Improve strain
Klaenhammer, 1998). The information performance and activity.
gleaned from sequence data will provide
Conduct studies with consumers to understand how best to communicate the concept of probiotics
opportunity to improve probiotic func-
and to determine favorable probiotic formats.·
tionality and expand understanding of
mechanisms. Conduct research to improve product formats, consumer acceptance, stability, and efficacy of
probiotic-containing products.
The application of gene-based tech-



studies, however, have focused on popu- tions lead to serious sequelae, probiotic Dong, M.-Y., Chang, T.-W., and Gorbach, S.L. 1987. Ef-
lations with a disease or lactase deficien- bacteria may add a low-cost, low risk lay- fects of feeding lactobacillus GG on lethal irradiation in
mice. Diagn. Microbiol. Infect. Dis. 7: 1–7.
cy, necessitating extrapolation of results er of protection from infection and dis- Donnet-Hughes, A., Rochat, F., Serrant, P., Aeschlimann,
to healthy or lactase-sufficient popula- ease. J. M., and Schiffrin, E.J. 1999. Modulation of nonspe-
tions. cific mechanisms of defense by lactic acid bacteria: Ef-
Human data on anti-hypertensive ef- fective dose. J. Dairy Sci. 82: 863–869.
REFERENCES Elmer, G.W., Surawicz, C.M., and McFarland, L.V. 1996.
fects, cholesterol-lowering, urogenital Adachi, S. 1992. Lactic acid bacteria and the control of Biotherapeutic agents: A neglected modality for the
health, inhibition of H. pylori, and im- tumours. In “The Lactic Acid Bacteria in Health and treatment and prevention of selected intestinal and vag-
mune function are not comprehensive Disease,” Vol. 1, ed. B.J.B. Wood, p. 233–261, Elsevi- inal infections. J. Amer. Med. Assn. 275: 870–876.
enough to be considered definitive, al- er Applied Science, London. Elmer, G.W., McFarland, L., and Surawicz, C.M. 1999.
Adams, M. R. and Marteau, P. 1995. On the safety of “Biotherapeutic Agents and Infectious Diseases,” Hu-
though results generated to date are suf- lactic acid bacteria from food. Intl. J. Food Microbiol. mana Press, Inc., Totawa, N.J.
ficiently positive to warrant further in- 27: 263–264. Eyssen, H. 1973. Role of gut microflora in metabolism of
vestigation. Anti-cancer activity has pri- Aguirre, M. and Collins, M.D. 1993. Lactic acid bacteria lipids and sterols. Proc. Nutr. Soc. 32: 59–63.
marily been documented in vitro and in and human clinical infection. J. Appl. Bacteriol. 75: Fonden, R., Mogensen, G., Tanaka, R., and Salminen, S.
animal models, although several lines of 95–107. 1999. Effect of fermented dairy products on intestinal
Aiba, Y., Suzuki, N., Kabir, A.M.A., Takagi, A., and Koga, microflora, human nutrition and health. Intl. Dairy Fed-
research, including one human study on Y. 1998. Lactic acid-mediated suppression of Helico- eration Bulletin, In Press.
cancer recurrence (Aso and Akazan, bacter pylori by the oral administration of Lactobacillus Fukushima, Y., Kawata, Y., Hara, H., Terada, A., and Mit-
1992), suggest that probiotic bacteria salivarius as a probiotic in a gnotobiotic murine model. suoka, T. 1998. Effect of a probiotic formula on intesti-
may be able to mediate this effect. Epi- Amer. J. Gastroenterol. 93: 2097–2101. nal imunoglobulin A production in healthy children. Intl.
Altekruse, S.F., Stern, N.J., Fields, P.I., and Swerdlow, J. Food Microbiol. 42: 39–44.
demiological studies have not been con- D.L. 1999. Campylobacter jejuni–An emerging food- Fuller, R. 1998. Probiotics for farm animals. In “Probiot-
ducted but are important for assessing borne pathogen. Emerging Infect. Dis. 5: 28–35. ics: A Critical Review,” ed G.W. Tannock, pp. 15–22,
the effect that regular consumption of Anderson, J.W. and Gilliland, S.E. 1999. Effect of fer- Horizon Scientific Press, Wymondham, U.K.
probiotic bacteria may have in generally mented milk (yogurt) containing Lactobacillus acidophi- Gade, J. and Thorn, P. 1989. Paraghurt for patients with
healthy populations. Opportunity for lus L1 on serum cholesterol in hypercholesterolemic irritable bowel syndrome. Scand. J. Prim. Health Care
humans. J. Amer. Coll. Nutr. 18: 43–50. 7: 23–26.
such investigation exists in countries, Aso, Y. and Akazan, H. 1992. Prophylactic effect of a Gasser, F. 1994. Safety of lactic acid bacteria and their
such as Japan, with a relatively high den- Lactobacillus casei preparation on the recurrence of occurrence in human clinical infections. Bull. Inst. Pas-
sity of long-time consumers of probiotic superficial bladder cancer. Urol. Intl. 49: 125–129. teur 92: 45–67.
products. Baricault, L., Denariaz, G., Houri, J.-J, Bouley, C., Sapin, Gilliland, S.E., Nelson, C.R., and Maxwell, C. 1985. As-
C., and Trugnan, G. 1995. Use of HT-29, a cultured similation of cholesterol by Lactobacillus acidophilus.
Probiotics have the potential to be human colon cancer cell line, to study the effect of fer- Appl. Environ. Microbiol. 49: 377–381.
exciting ingredients for foods with a mented milks on colon cancer cell growth and differen- Giraffa, G., Carminati, D., and Neviani, E. 1997. Entero-
“healthy” image. Probiotics could be tiation. Carcinogenesis 16: 245–252. cocci isolated from dairy products: A review of risks
combined with other healthful ingredi- Bellomo, G., Mangiale, A., Nicastro, L., and Frigerio, G. and potential technological use. J. Food Protect. 60:
ents or simply used to complement the 1980. A controlled double-blinded study of SF68 732–738.
strain as a new biological preparation for the treatment Goldin, B.R., Gualtieri, L.J., and Moore, R.P. 1996. The
natural functional attributes of whole of diarhhea in pediatrics. Curr. Therapeutic Res. 28: effect of Lactobacillus GG on the initiation and promo-
foods. The combination of probiotic 927-936. tion of DMH-induced intestinal tumors in the rat. Nutr.
bacteria with nutrient-dense foods, such Bengmark, S. 1998. Ecological control of the gastrointesti- Cancer 25: 197–204.
as dairy products, will have the added nal tract. The role of probiotic flora. Gut 42: 2–7. Goldin, B.R., Swenson, L., Dwyer, J., Sexton, M., and
Bengmark, S. and Gianotti, L. 1996. Nutritional support Gorbach, S. 1980. Effect of diet and Lactobacillus aci-
benefit of enhancing consumer nutri-
to prevent and treat multiple organ failure. World J. dophilus supplements on human fecal bacterial en-
tion. Consumer awareness of probiotics Surg. 20: 474–481. zymes. J. Natl. Cancer Inst. 64: 255–261.
in the United States is minimal. There- Bibel, D.J. 1988. Elie Metchnikoff’s bacillus of long life. Hallen, A., Jarstrand, C., and Pahlson, C. 1992. Treat-
fore, success with probiotics in the Unit- ASM News 54: 661–665. ment of bacterial vaginosis with lactobacilli. Sex. Trans.
ed States will require consumer educa- Bruce, A.W. and Reid, G. 1988. Intravaginal instillation of Dis. 19: 146–148.
lactobacilli for prevention of recurrent urinary tract in- Hata, Y., Yamamoto, M., Ohni, M., Nakajima, K., Nakamu-
tion, which could also contribute to fections. Can. J. Microbiol. 34: 339–343. ra, Y., and Takano, T. 1996. A placebo-controlled study
changing the common perception that Buchanan, R.L. and Doyle, M.P. 1997. Foodborne dis- of the effect of sour milk on blood pressure in hyper-
“bacteria are bad.” ease significance of Escherichia coli O157:H7 and tensive subjects. Amer. J. Clin. Nutr. 64: 767–771.
The vast array of health benefits at- other enterohemorrhagic E. coli. A Scientific Status Henriksson, R., Franzen, L., Sandstrom, K., Nordin, A.,
Summary by the Institute of Food Technologists Expert Arevarn, M., and Grahn, E. 1995. Effects of active ad-
tributed to probiotics may seem implau-
Panel on Food Safety and Nutrition, Chicago, Ill., Food dition of bacterial cultures in fermented milk to patients
sible. However, when considering that Technol. 51(10): 69–76. with chronic bowel discomfort following irradiation.
many of the effects of probiotic bacteria Cano, R. and Willoughby, V. 1999. Sequencing the ge- Support Care Cancer 3: 81–83.
stem from influence on the balance or nome of Lactobacillus acidophilus. J. Dairy Sci. 82: 6, Hentges, D.J. 1992. Gut flora and disease resistance. In
activity of the gut microflora, it is easier abstract #D101. “Probiotics: The Scientific Basis,” ed R. Fuller, pp. 87–
DeSimone, C., Vesely, R., Bianchi-Salvidori, B., and Jiril- 109, Chapman and Hall, London.
to comprehend the broad-reaching pos- low. E. 1993. The role of probiotics in modulation of Hill, M.H., Draser, B.S., Aries, V., Crowther, J.S., Hawk-
tulated effects. The ability of probiotic the immune system in man and in animals. Intl. J. Im- sworth, G., and Williams, R.E.O. 1971. Bacteria and
bacteria to modulate these activities is munotherapy IX: 23–28. etiology of cancer of large bowel. Lancet January: 95–
being established. DeSmet, I., Van Hoorde, L., De Saeyer, N., Van de 100.
Woestyne, M., and Verstraete, W. 1994. In vitro study Hillier, S.L., Krohn, M.A., Klebanoff, S.J., and Eschenbach,
In a climate of the trend toward re-
of bile salt hydrolase (BSH) activity of BSH isogenic D.A. 1992. The relationship of hydrogen peroxide-pro-
duced antibiotic use, awareness of dis- Lactobacillus plantarum 80 strains and estimation of ducing lactobacilli to bacterial vaginosis and genital mi-
ease resulting directly from microecosys- cholesterol lowering through enhanced BSH activity. croflora in pregnant women. Obstetrics Gynecol. 79:
tem disruption, emergence of pathogens Microbial Ecol. Health Dis. 7: 315–329. 369–373.
with enhanced virulence, clinical condi- Dias, R.S., Bambirra, E.A., Silva, M.E., and Nicoli, J.R. Hillier, S.O., Nugent, R.P., Eschenbach, D.A., Krohn, M.A.,
1995. Protective effect of Saccharomyces boulardii Gibbs, R.S., Martin, D.H., Cotch, M.F., Edelman, R.,
tions refractory to conventional treat- against the cholera toxin in rats. J. Med. Biolog. Res. Pastorek, J.G., Rao, A.V., NcNellis, D., Regan, J.A.,
ment, and awareness that some infec- 28: 323-325. Carey, J.C., and Klebanoff, M.A. 1995. Association be-



Probiotics taining remission of ulcerative colitis. Aliment. Pharma-

col. Ther. 11: 853–858.
Lai, K.K. 1996. Antibiotic-resistant enterococci and the
Mital, R.K. and Garg, S.K. 1995. Anticarcinogenic, hypo-
cholesterolemic, and antagonistic activities of Lactoba-
cillus acidophilus. Crit. Rev. Microbiol. 21: 175–214.
C O N T I N U E D changing face of surgical infections. Arch. Surg. 156: Muting, D., Eschrich, W., and Mayer, J.-B. 1968. The ef-
338-342. fect of bacterium bifidum on intestinal bacterial flora
Lee, Y.-K, Nomoto, K., Salminen, S., and Gorbach, S.L. and toxic protein metabolites in chronic liver disease.
1999. “Handbook of Probiotics,” John Wiley & Sons, Amer. J. Proct. 19(5): 336–342.
Inc., N.Y. Naidu, A.S., Bidlack, W.R., and Clemens, R.A. 1999.
tween bacterial vaginosis and preterm delivery of a Ling, W.H., Korpela, R., Mykkanen, H., Salminen, S., and Probiotic spectra of lactic acid bacteria (LAB). CRC
low-birth-weight infant. N. Engl. J. Med. 333: 1737– Hanninen, O. 1994. Lactobacillus strain GG supple- Crit. Rev. Food Sci. Nutr. 39: 13–126.
1742. mentation decreases colonic hydrolytic and reductive Nakamura, Y., Masuda, O., and Takano, T. 1996. De-
Hilton, E., Isenberg, H.D., Alperstein, P., France, K., and enzyme activities in healthy female adults. J. Nutr. 124: crease of tissue angiotensin-I-converting enzyme activ-
Borenstein, M.T. 1992. Ingestion of yogurt containing 18–23. ity upon feeding sour milk in spontaneously hyperten-
Lactobacillus acidophilus as prophylaxis for candidal Link-Amster, H., Rochat, F., Saudan, K.Y., Mignot, O., sive rats. Biosci. Biotechnol. Biochem. 60: 488–489.
vaginitis. Ann. Intern. Med. 116: 353–357. and Aeschlimann, J.M. 1994. Modulation of a specific Nakamura, Y., Yamamoto, N., Sakai, K., and Takano, T.
Hirayama, K. and Rafter, J. 1999. The role of lactic acid humoral immune response and changes in intestinal 1995. Antihypertensive effect of sour milk and pep-
bacteria in colon cancer prevention: Mechanistic con- flora mediated through fermented milk intake. FEMS tides isolated from it that are inhibitors to angiotensin-I-
siderations. Antonie van Leeuwenhoek 76: 391–394. Immunol. Med. Microbiol. 10: 55–64. converting enzyme. J. Dairy Sci. 78: 1253–1257.
Holzapfel, W.H., Haberer, P., Snel, J., Schillinger, U., Huis Majamaa, H., Isolauri, E., Saxelin, M., and Vesikari, T. Nanji, A.A., Khettry, U., and Sadrzadeh, S.M.H. 1994.
in’t Veld, J.H.J.1998. Overview of gut flora and probi- 1995. Lactic acid bacteria in the treatment of acute Lactobacillus feeding reduces endotoxemia and severi-
otics. Intl. J. Food Microbiol. 41: 85–101. rotavirus gastroenteritis. J. Ped. Gastroenterol. Nutr. 20: ty of experimental alcoholic liver (disease). Proc. Soc.
Isolauri, E., Joensuu, J., Suomalainen, H., Luomala, M., 333–338. Exp. Biol. Med. 205: 243–247.
Vesikari, T. 1995. Improved immunogenicity of oral D x Malin, M., Suomalainen, H., Saxelin, M., and Isolauri, E. Oksanen, P.J., Salminen, S., Saxelin, M., Hamalainen, P.,
RRV reassortant rotavirus vaccine by Lactobacillus 1996. Promotion of IgA immune response in patients Ihantola-Vormisto, A., Muurasniemi-Isoviita, L., Nikkari,
casei GG. Vaccine 13: 310–312. with Crohn’s disease by oral bacteriotherapy with Lac- S., Oksanen, T., Porsti, I., Salminen, E., Siitonen, S.,
Isolauri, E., Kaila, M., Arvola, T., Majamaa, H., Rantala, I., tobacillus GG. Ann. Nutr. Metab. 40: 137–145. Stuckey, H., Toppila, A., and Vapaatalo, H. 1990. Pre-
Virtanen, E., and Arvilommi, H. 1993a. Diet during ro- Marshall, B.J. 1994. Helicobacter pylori. Amer. J. Gastro- vention of travelers diarrhea by Lactobacillus GG. Ann.
tavirus enteritis affects jejunal permeability to macro- enterol. 89: S116–S128. Med. 22: 53–56.
molecules in suckling rats. Pediatr. Res. 33: 548–553. Marteau, P. and Rambaud, J.-C. 1993. Potential of using Orrhage, K., Brismar, B., and Nord, C.E. 1994. Effect of
Isolauri, E., Majamaa, H., Arvola, T., Rantala, I., Virtanen, lactic acid bacteria for therapy and immunomodulation supplements with Bifidobacterium longum and Lacto-
E., and Arvilommi, H. 1993b. Lactobacillus casei strain in man. FEMS Microbiol. Rev. 12: 207–220. bacillus acidophilus on the intestinal microbiota during
GG reverses increased intestinal permeability induced Marteau, P., Minekus, M., Havenaar, R., and Huis in‘t administration of clindamycin. Microbial. Ecol. Health
by cow milk in suckling rats. Gastroenterol. 105: Veld, J.H.J. 1997. Survival of lactic acid bacteria in a Dis. 7: 17–25.
1643–1650. dynamic model of the stomach and small intestine: Val- Ouwehand, A.C. and Salminen, S.J. 1998. The health ef-
Jung, L.K. 1999. Lactobacillus GG augments the im- idation and the effect of bile. J. Dairy Sci. 80: 1031– fects of cultured milk products with viable and non-via-
mune response to typhoid vaccination: A double-blind- 1037. ble bacteria. Intl. Dairy J. 8: 749–756.
ed, placebo-controlled study. Presented at Experimen- McBean, L.D. 1998. Dairy foods: Traditional and emerg- Parashar, U.D., Bresee, J.S., Gentsch, J.R., and Glass, R.I.
tal Biology ‘99, Washington, D.C., Apr. 17-20, Abst. ing health benefits. Dairy Council Digest 69(5): 25–30. 1998. Rotavirus. Emer. Infect. Dis. 4: 561–570.
659.8. McBean, L.D. 1999. Emerging dietary benefits of dairy Pelto, L., Salminen, S.J., and Isolauri, E. 1996. Lactoba-
Kabir, A.M.A., Aiba, Y., Takagi, A., Kamiya, S., Miwa, T., foods. Nutr. Today. 34(1): 47-53. cillus GG modulates milk-induced immune inflammato-
and Koga, Y. 1997. Prevention of Helicobacter pylori McConnell, M.A. and Tannock, G.W. 1993. A note on ry response in milk-hypersensitive adults. Nutr. Today
infection by lactobacilli in a gnotobiotic murine model. lactobacilli and ß-glucuronidase activity in the intestinal Suppl. 31: 45S–46S.
Gut 41: 49–55. contents of mice. J. Appl. Bacteriol. 74: 649–651. Perdigón, G., Alvarez, S., Rachid, M., Agüero, G., and
Kaila, M., Isolauri, E., Soppi, E., Virtanen, E., Saine, S., and McCracken, B.J. and Gaskins, H.R. 1999. Probiotics and Gobbato, N. 1995. Immune system stimulation by pro-
Arvilommi, H. 1992. Enhancement of the circulating an- the immune system. In “Probiotics: A Critical Review,” biotics. J. Dairy Sci. 78: 1597–1606.
tibody secreting cell response in human diarrhea by a ed G.W. Tannock, pp. 85–111, Horizon Scientific Perdigón, G. and Alvarez, S. 1992. Probiotics and the im-
human lactobacillus strain. Pediatr. Res. 32: 141–144. Press, Norfolk, England. mune state. In “Probiotics: The Scientific Basis.” ed R.
Kaila, M., Isolauri, E., Saxelin, M., Arvilommi, H., and McFarland, L.V., Surawicz, C.M., Greenberg, R.N., Fekety, Fuller, pp.145–179, Chapman and Hall, London.
Vesikari, T. 1995. Viable versus inactivated lactobacillus R., Elmer, G.W., Moyer, K.A., Melcher, S.A., Bowen, Rafter, J.J. 1995. The role of lactic acid bacteria in colon
strain GG in acute rotavirus diarrhoea. Arch. Dis. Child. K.E., Cox, J.L., Noorani, Z., Harrington, G., Rubin, M., cancer prevention. Scand. J. Gastroenterol. 30: 497–
72: 51-53. and Greenwald, D. 1994. A randomized placebo-con- 502.
Kishi, A., Uno, K., Matsubara, Y., Okuda, C., and Kishida, trolled trial of Saccharomyces boulardii in combination Rao, C.V., Sanders, M.E., Indranie, C., Simi, B., and Red-
T. 1996. Effect of the oral administration of Lactobacil- with standard antibiotics for Clostridium difficile disease. dy, B.S. 1999. Prevention of indices of colon carcino-
lus brevis subsp. coagulans on interferon a-producing J. Amer. Med. Assn. 271(24): 1913–1918. genesis by the probiotic Lactobacillus acidophilus
capacity in humans. J. Amer. Coll. Nutr. 15: 408–412. McNamara, S.H. 1998. So you want to market a food NCFMTM in rats. Intl. J. Oncol. 14: 939–944.
Kitts, C.L. 1999. 16S rDNA TRF patterns, a DNA-based and to make health-related claims–How far can you Rasic, J.L., Vujicic, I.F., Skrinjar, M., and Vulic, M. 1992.
method to describe bacterial communities: Applications go? What rules of law will govern the claims you want Assimilation of cholesterol by some cultures of lactic
to definition of probiotic function. J. Dairy Sci. 82: 6, to make? Food Drug Law J. 53: 421–436. acid bacteria and bifidobacteria. Biotechnol. Lett. 14:
abstract #D98. Merger, M. and Croitoru, K. 1998. Infections in the im- 39–44.
Klaenhammer, T.R. 1995. Genetics of intestinal lactoba- munopathogenesis of chronic inflammatory bowel dis- Read, A. E., McCarthy, C. F., Heaton, K.W., and Laidlaw,
cilli. Intl. Dairy J. 5: 1019–1058. ease. Sem. Immunol. 10: 69–78. J. 1966. Lactobacillus acidophilus (Enpac) in treatment
Klaenhammer, T.R. 1998. Functional activities of Lacto- Michetti, P., Dorta, G., Wiesel, P.H., Brassart, D., Verdu, of hepatic encephalopathy. Brit. Med. J. 1: 1267–
bacillus probiotics: Genetic mandate. Intl. Dairy J. 8: E., Herranz, M., Felley, C., Porta, N., Rouvet, M., Blum, 1269.
497–505. A.L., and Corthesy-Theulaz, I. 1999. Effect of whey- Reddy, B. S. and Rivenson, A. 1993. Inhibitory effect of
Klaver, F.A.M. and Meer, R.V. 1993. The assumed assim- based culture supernatant of Lactobacillus acidophilus Bifidobacterium longum on colon, mammary, and liver
ilation of cholesterol by lactobacilli and Bifidobacterium (johnsonii) La1 on Helicobacter pylori infection in hu- carcinogenesis induced by 2-amino-3 methylimidazo
is due to their bile salt-deconjugating activity. Appl. En- mans. Digestion. In Press. [4,5]quinoline, a food mutagen. Canc. Res. 53: 3914–
viron. Microbiol. 59: 1120–1124. Midolo, P.D., Lambert, J.R., Hull, R., Luo, F., and Gray- 3918.
Korschunov, V.M., Smeyanov, V.V., Efimov, B.A., Tarabrina, son, M.L. 1995. In vitro inhibition of Helicobacter py- Reid, G., Bruce, A.W., and Taylor, M. 1995. Instillation of
N.P., Ivanov, A.A., and Baranov, A.E. 1996. Therapeu- lori NCTC 11637 by organic acids and lactic acid bac- Lactobacillus and stimulation of indigenous organisms
tic use of an antibiotic-resistant Bifidobacterium prepa- teria. J. Appl. Bacteriol. 79: 475–479. to prevent recurrence of urinary tract infections. Micro-
ration in men exposed to high-dose g-irradiation. J. Minekus, M., Marteau, P., Havenaar, R., and Huis in’t ecol. Ther. 23: 32–45.
Med. Microbiol. 44: 70–74. Veld, J.H.J. 1995. A multicompartmental dynamic Reid, G., Bruce, A.W., and Smeianov, V. 1998. The role
Kruis, W., Schutz, E., Fric, P., Fixa, B., Judmaier, G., and computer-controlled model simulating the stomach and of lactobacilli in preventing urogenital and intestinal in-
Stolte, M. 1997. Double-blind comparison of an oral small intestine. Alternative To Laboratory Animals 23: fections. Intl. Dairy J. 8: 555–562.
Escherichia coli preparation and mesalazine in main- 197–209. Renner, H.W. and Munzner, R. 1991. The possible role of



probiotics as dietary antimutagens. Mutation Res. 262: eases,” ed. G.W. Elmer, L. McFarland, and C. Surawicz, consumption on populations of young and elderly
239–245. p. 221–244, Humana Press Inc., Totowa, N.J.. adults. Intl. J. Immunother. IX: 53–64.
Rolfe, R.D. 1995. Probiotics: Prospects for use in Solis-Pereyra, B. and Lemonnier, D. 1993. Induction of Van der Meer, R., Bovee-Oudenhoven, I.M.J., Sesink,
Clostridium difficile-associated intestinal disease. In: human cytokines by bacteria used in dairy foods. Nutr. A.L.A., and Kleibeuker, J.H. 1998. Milk products and
“Probiotics: Prospects of Use in Opportunistic Infec- Res. 13: 1127–1140. intestinal health. Intl. Dairy J. 8: 163–170.
tions,” ed. R. Fuller, P.J. Heidt, V. Rusch, and D.V.D. Solis-Pereyra, B., Aattouri, N., and Lemonnier, D. 1997. Vanderhoof, J.A. and Young, R.J. 1998. Use of probiotics
Waaij, pp. 47–66, Institute for Microecology, Herborn, Role of food in the stimulation of cytokine production. in childhood gastrointestinal disorders. J. Pediatr. Gas-
Germany. Am. J. Clin. Nutr. 66: 521S–525S. troenterol. Nutr. 27: 323-332.
Rossouw, J.E., Burger, E.-M., Van Der Vyver, P., and Fer- Spanhaak, S., Havenaar, R., and Schaafsma, G. 1998. Venturi, M., Hambly, R.J., Glinghammar, B., Rafter, J.J.,
reira, J.J. 1981. The effect of skim milk, yoghurt, and The effect of consumption of milk fermented by Lacto- and Rowland, I.R. 1997. Genotoxic activity in human
full cream milk on human serum lipids. Am. J. Clin. bacillus casei strain Shirota on the intestinal microflora faecal water and the role of bile acids: A study using
Nutr. 34: 351–356. and immune parameters in humans. Europ. J. Clin. the alkaline comet assay. Carcinogenesis 18: 2353–
Rowland, I.R., Rumney, C.J., Coutts, J.T., and Lievense, Nutr. 52: 899–907. 2359.
L.C. 1998. Effect of Bifidobacterium longum and inulin Suarez, F.L., Savaiano, D.A., and Levitt, M.D. 1995. The Vollaard, E.J. and Clasener, H.A.L. 1994. Colonization re-
on gut bacterial metabolism and carcinogen-induced treatment of lactose intolerance. Aliment. Pharmacol. sistance. Antimicrobial Agents Chemother. 38: 409–
aberrant crypt foci in rats. Carcinogenesis 19: 281– Ther. 9: 589–597. 414.
285. Tahri, K., Grill, J.P., and Schneider, F. 1996. Bifidobacte- Wells, C.L., Maddaus, M.A., and Simmons, R.L. 1988.
Saavedra, J.M., Bauman, N.A., Oung, I., Perman, J.A., ria strain behavior toward cholesterol: Coprecipitation Proposed mechanisms for the translocation of intestinal
and Yolken, R.H. 1994. Feeding of Bifidobacterium bi- with bile salts and assimilation Curr. Microbiol. 33: bacteria. Rev. Infect. Dis. 10: 958–979.
fidum and Streptococcus thermophilus to infants in 187–193. Wheeler, J.G., Shema, S.J., Bogle, M.L., Shirrell, M.A.,
hospital for prevention of diarrhoea and shedding of ro- Takano, T. 1998. Milk derived peptides and hypertension Burks, A.W., Pittler, A., and Helm, R. M. 1997. Immune
tavirus. Lancet 344:1046–1049. reduction. Intl. Dairy J. 8: 375–381. and clinical impact of Lactobacillus acidophilus on
Salminen, S. and von Wright, A. 1998. Current probiotics Tannock, G.W. 1983. Effect of dietary and environmental asthma. Ann. Allergy Asthma Immunol. 19: 229–233.
—safety assured? Microbial Ecol. Health Dis. 10: 68– stress on the gastrointestinal microbiota. In “Human In- Williams, G.M. and Wynder, E.L. 1996. Diet and cancer:
77. testinal Microflora in Health and Disease,” ed. D.J. A synopsis of causes and prevention strategies. In “Nu-
Salminen, E., Elomaa, E., Minkkinen, J., Vapaatalo, H., Hentges, pp. 517–539, Academic Press, Inc., London. trition and Cancer Prevention,” ed. R.R. Watson and
and Salminen, S. 1988. Preservation of intestinal integ- Tannock, G.W. 1990. The microecology of lactobacilli in- S.I. Mufti, pp. 1–23. CRC Press, Inc., Boca Raton, Fla.
rity during radiotherapy using live Lactobacillus acido- habiting the gastrointestinal tract. Adv. Microb. Ecol. Yeung, P.S.M., Cano, R., Tong, P.S., and Sanders, M.E.
philus cultures. Clin. Radiol. 39: 435–437. 11: 147–171. 1999. Comparison of API, 16S rDNA sequencing and
Salminen, S., Isolauri, E., and Salminen, E. 1996. Clinical Tannock, G.W. 1994. More than a smell: The complexity fatty acid analysis as methods to speciate commercial
uses of probiotics for stabilizing the gut mucosal barri- of the normal microflora. In “Normal Microflora. An In- probiotic bacteria. J. Dairy Sci. 82: 6, abstract #D22.
er: Successful strains and future challenges. Antonie troduction to Microbes Inhabiting the Human Body,” ed. Zink, R. 1998. Personal communication. Nestlé, Lau-
von Leeuwenhoek 70: 347-358. G.W. Tannock, pp 1–36, Chapman and Hall, London. sanne, Switzerland. ●
Salminen, S., Bouley, C., Boutron-Ruault, M.-C., Cum- Tannock, G.W. 1999a. “Probiotics A Critical Review.” Ho-
mings, J.H., Franck, A., Gibson, G.F.R., Isolauri, E., rizon Scientific Press, Norfolk, England. Acknowledgments
Moreau, M.-C., Roberfroid, M., and Rowland, I. 1998. Tannock, G.W. 1999b. The intestinal microflora. In “Probi- The author acknowledges the following individuals for
Functional food science and gastrointestinal physiology otics A Critical Review,” ed. G.W. Tannock, pp. 5–14, their helpful comments during manuscript preparation: D.
and function. Brit. J. Nutr. 80 (suppl. 1): S147–S171. Horizon Scientific Press, Norfolk, England. Berry, Dairy Foods Magazine (DesPlaines, Ill.); S. Bush,
Salminen, S., Ouwehand, A., Benno, Y., and Lee, Y.K. Tannock, G.W., Crichton, C., Welling, G.W., Koopman, Rhodia, Inc. (Madison, Wis.); J. Heimbach, Environ
1999. Probiotics: How should they be defined? Trends J.P., and Midtvedt, T. 1988. Reconstitution of the gas- (Arlington, Va.); L. Kam, Cedar Sanai Med. Ctr. (Los
Food Sci. Technol. 10: 107–110. trointestinal microflora of lactobacillus-free mice. Appl. Angeles, Calif.); T. Klaenhammer, N. Carolina State Univ.
Sanders, M.E. 1998a. Overview of functional foods: Em- Environ. Microbiol. 54: 2971–2975. (Raleigh, N.C.); L. Morelli, Instituto di Microbiologica
phasis on probiotic bacteria. Intl. Dairy J. 8: 341–347. Targan, R. and Shanahan, F. 1994. “Inflammatory Bowel (Piacenza, Italy); J. O’Donnell, Calif. Dairy Res. Foundation
Sanders, M.E. 1998b. Development of consumer probi- Disease from Bench to Bedside.” Williams & Wilkins, (Davis, Calif.); L. Petersen, Chr. Hansens (Milwaukee,
otics for the U.S. market. Brit. J. Nutr. 80 (Suppl. 1): Baltimore, Md. Wis.); G. Reid, Univ. Western Ontario (London, Ontario,
S213–S218. Taylor, G.R.J. and Williams, C.M. 1998. Effects of probiot- Canada); W. Sandine, Temecula, Calif.; G. Tannock, Univ.
Sanders, M.E. and Huis in’t Veld, J. 1999. Bringing a ics and prebiotics on blood lipids. Brit. J. Nutr. 80 (Sup- Otago (Dunedin, New Zealand); and R. Zink, Nestlé
probiotic-containing functional food to the market: Mi- pl. 1): S225–S230. (Lausanne, Switzerland). The author also acknowledges
crobiological, product, regulatory and labeling issues. Trapp, C.L., Chang, C.C., Halpern, G.M., Keen, C.L., and the California Dairy Research Foundation for its support of
Antonie van Leeuwenhoek 76: 293–315. Gershwin, M.E. 1993. The influence of chronic yogurt probiotic-specific research in her laboratory at Cal Poly.
Sawada, H., Furushiro, M., Hirai, K., Motoike, M., Wa-
tanabe, T., and Yokokura, T. 1990. Purification and
characterization of an antihypertensive compound from
Lactobacillus casei. Agric. Biol. Chem. 54: 3211–
Saxelin, M., Chuang, M.H., Chassy, B., Rautelin, H.,
Makela, P.H., Salminen, S., and Gorbach, S.L. 1996.
Lactobacilli and bacteremia in Southern Finland, 1989-
1992. Clin. Infect. Dis. 22: 564-566. The Society for Food Science and Technology
Schiffrin, E.J., Rochat, F., Link-Amster, H., Aeschlimann,
221 N. LaSalle St., Ste. 300, Chicago, IL 60601-1291 USA
J.M., and Donnet-Hughes, A. 1995. Immunomodula-
tion of human blood cells following the ingestion of lac- Tel. 312-782-8424 • Fax: 312-782-8348
tic acid bacteria. J. Dairy Sci. 78: 491–497. E-mail: • URL:
Shalev, E., Battino, S., Weiner, E., Colodner, R., and Ke- This and other Scientific Status Summaries are published by the Institute of Food Technologists’
ness, Y. 1996. Ingestion of yogurt containing Lactoba-
cillus acidophilus compared with pasteurized yogurt as Expert Panel on Food Safety and Nutrition in Food Technology. Scientific Status Summaries, which
prophylaxis for recurrent candidal vaginitis and bacterial are not necessarily written by the Expert Panel, are rigorously peer-reviewed by the Expert Panel
vaginosis. Arch. Fam. Med. 5: 593–596. as well as by individuals outside the panel who have specific expertise in the subject. IFT’s Expert
Simenhoff, M.L., Dunn, S.R., Zollner, G.P., Fitzpatrick, Panel on Food Safety and Nutrition, which studies significant food-related issues and oversees
M.E.D., Emery, S.M., Sandine, W.E., Ayres, J.W. 1996.
timely production of Scientific Status Summaries, comprises academicians representing exper-
Biomodulation of the toxic and nutritional effects of
small bowel bacterial overgrowth in end-stage kidney tise in one or more areas of food science/technology and nutrition.
disease using freeze-dried Lactobacillus acidophilus. The Scientific Status Summaries may be reprinted or photocopied without permission, provided
Miner. Electrolyte Metab. 22: 92–96. that suitable credit is given.
Sobel, J.D. 1999. Biotherapeutic agents as therapy for
vaginitis. In “Biotherapeutic Agents and Infectious Dis-