D'dragon Health Product: Jul 25, 2008

Making Sense of Probiotics

Consider for a moment that the human gut contains 10 times more bacteria than all the human cells in the entire body.

1. The intestinal tract is home to approximately 100,000,000,000,000 (100 trillion)

Micro-organisms.

2. This enormous biomass consists of over 400 known diverse bacterial species that generate intense metabolic activity and are of key importance for human health.1 In addition to promoting normal gastrointestinal functions and providing protection from infection, the intestinal microflora also exerts important effects on systemic metabolism and immune function. While the exact roles of many of these organisms are not yet clearly understood, basic scientific and clinical research is beginning to characterize the diverse functions

of normal intestinal micro-biota.

Pro-biotics are either member species of the essential intestinal micro-flora or they are transient species affecting benefit as they pass through the gastrointestinal tract.

PROBIOTICS - Definition and Species

In the early 1900s, the Nobel laureate Metchnikoff reported favorable health effects and improved longevity from consuming fermented milk products.

3. He suggested that ingestion of live lactic acid bacteria may improve the balance of the gastrointestinal micro-flora. In 1965,Lilly and Stillwell introduced the term “pro-biotics” for growth promoting factors produced by microorganisms.

4. Fuller popularized the word “probiotic” in 1989, describing pro-biotics as live microbial feed supplements, which benefit the host by improving intestinal microbial balance.

5. In 2001, an International Life Sciences Institute Europe consensus document proposed a simple and now widely accepted definition of probiotics as “viable microbial food supplements which beneficially influence

the health of humans.”

6. Probiotics consist of lactic acid producing bacteria (LAB), non-lacticacid producing bacterial species,

and non-pathogenic yeast.

LACTIC ACID PRODUCING PROBIOTICS

Lactobacillus

The genus Lactobacillus normally predominates in the small intestine.Lactobacillus species are facultative anaerobes although some species,such as Lactobacillus plantarum, can respire oxygen turning it into

hydrogen peroxide. Of the more than 100 Lactobacillus species, the following are commonly used probiotics:

L. acidophilus L. fermentum L. paracasei

L. brevis L. gasseri L. plantarum

L. bulgaricus L. helveticus L. reuteri

L. casei L. jensenii L. rhamnosus

L. crispatus L. johnsonii L. salivarius

Bifidobacterium

Bifidobacterium is another well-documented genus of lactic acid producing bacteria. Bifidobacteria are strictly anaerobic and normally vie for predominance in the large intestine. The following 8 of the more than 30 Bifidobacterium species are frequently used as probiotics:

B. adolescentis B. breve B. longum

B. animalis B. infantis B. thermophilum

B. bifidum B. lactis

Streptococcus

Streptococcus species are not typically associated with health benefits and often highly pathogenic. However, one facultative anaerobic species, Streptococcus thermophilus, is known to promote health.

It is one of the two primary species found in yogurt cultures, the other being L. bulgaricus.

Enterococcus

Found in a number of probiotic products, the facultative anaerobe Enterococcus faecium has a variety of beneficial characteristics. However, E. faecium has evolved from a relatively nonpathogenic commensal bacteria to the third most common cause of hospital acquired infections and now accounts for over 10% of enterococcal clinical isolates.7,8 It has developed extensive resistance to antibiotics.

NON-LACTIC ACID-PRODUCING PROBIOTICS

Bacillus

Bacillus species are ubiquitous facultative or obligate aerobic,

spore-producing organisms found in the soil and water.9 Spores of a

number of Bacillus species are used as probiotics and are often referred

to as soil-based probiotics. A number of species including Bacillus

subtilis, B. coagulans, B. licheniformis, and B. cereus have shown benefit.

However, Bacillus species have well documented toxicities that include

the potential production of enterotoxins. Bacillus probiotic products

have been plagued by problems with mislabeling and associated with

gastroenteritis and diarrhea.9

Proprionibacterium

Proprionibacterium species are Gram-positive, nonsporing,

pleomorphic rods first described in 1906.10 Usually anaerobic, some

strains tolerate very small amounts of air (microaerophilic). Their

primary fermentation products are proprionic acid, acetic acid, and

carbon dioxide. Proprionibacterium species are commonly found on

the skin. Proprionobacteria stimulate the growth of bifidobacteria,

reduce pathogenic fecal Staphylococcus and Enterobacteriaceae

populations, decrease the fecal concentration of carcinogenic enzymes,

and favorably modulate the immune system. Select Proprionibacterium

species may have good potential as probiotics.

YEAST PROBIOTICS

Saccharomyces

The yeast genus Saccharomyces contains 7 or 10 species of which only

S. boulardii is used as a probiotic.11 Unaffected by gastric acid and bile,

S. boulardii proliferates along the entire gastrointestinal tract. It has

been used alone and in combination with other probiotics to

successfully manage a variety of gastrointestinal disorders especially

diarrhea and Clostridium difficile-associated disease.11,12

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PROBIOTICS - Major Species and Characteristics

Lactobacillus

Lactobacillus species are facultative anaerobic, Gram-positive,

non-spore forming rods or elongated ovals (coccobacilli). They are

characterized as homofermentative, meaning they primarily produce

lactic acid as a fermentation end-product, or heterofermentative,

meaning lactic acid, carbon dioxide, ethanol, and acetic acid are the

principal fermentation end-products.13 Since the advent of gene

typing and hybridization technologies, Lactobacillus classification has

evolved rapidly and there are presently over 100 accepted species.14

Lactobacilli possess many important features that make them valuable

probiotics. These include production of enzymes to digest and

metabolize proteins and carbohydrates, synthesis of B vitamins and

vitamin K, breakdown of bile salts, enhancement of innate and

acquired immunity, and inhibition of proinflammatory mediators.

Lactobacillus species exhibit antimicrobial activities against an array of

pathogens including Pseudomonas, Escherichia coli, Staphylococcus

aureus, Salmonella, Shigella, Candida, and Helicobacter pylori.

L. acidophilus is undoubtedly the best known probiotic. For decades a

variety of lactobacilli were misclassified as L. acidophilus. Only in

recent years have these organisms been recognized as distinct species

with distinguishing features and unique potential health benefits. One

confusing result of new, refined methods of microbial classification is

that many of the healthful effects long attributed to “L. acidophilus”are

now recognized to belong to other Lactobacillus species. One such

species, L. rhamnosus, is now appreciated as highly beneficial. It was

not until 1989 that L. rhamnosus was recognized as a separate species

and it was not viewed as beneficial for many years. Evolving

reclassification of “L. acidophilus” species was largely responsible for

the results of Hughes’ 1990 study of probiotics that found almost none

of the “L. acidophilus” probiotics tested contained L. acidophilus. The

most commonly identified species was L. rhamnosus.

L. rhamnosus strains are probably the most extensively studied

probiotics.Many studies have repeatedly found that L. rhamnosus GG

can treat and prevent rotavirus diarrhea, prevent antibiotic-associated

diarrhea, and treat diarrhea caused by Clostridium difficile.6,12,17

L. rhamnosus has significant immunomodulatory properties. The

effects of L. rhamnosus GG were examined in infants with allergies to

cow’s milk and atopic dermatitis and associated with significant

improvements compared to placebo.18 The probiotic reduced several

markers of intestinal inflammation in the infants possibly due to

improved intestinal barrier function leading to decreases in antigen

translocation. Two more recent studies have also demonstrated the

benefits of L. rhamnosus GG in preventing and treating atopic

dermatitis and eczema in infants.19,20

L. acidophilus was once thought to be indigenous to the human

gastrointestinal tract and that consuming L. acidophilus restocked the

intestines with normal microflora. L. acidophilus is now known not to

be indigenous to the bowel, but species previously classified as

L. acidophilus, such as L. gasseri, L. crispatus, and L. johnsonii, are

indigenous.21-23 Most Lactobacillus probiotics are not indigenous to

the human gastrointestinal tract, but colonize the intestines when

regularly consumed. Vegetarians and people ingesting traditional

plant-based diets have high colonization rates of certain lactobacilli

such as L. plantarum, L. rhamnosus, and L. acidophilus. Colonization

rates with these important microorganisms are low in individuals

consuming a standard highly processed Western. It is now clear that

probiotics must be regularly consumed to restore and maintain the

normal intestinal balance of essential microorganisms.

Bifidobacterium

Bifidobacteria were identified at the end of the 19th century as

irregular Y-shaped bacteria and termed Bacillus bifidus.24 For most of

the 20th century they were classified as members of the genus

Lactobacillus because they produced lactic acid. Numerous studies

detailing a unique physiology and nutritive requirements led to the

creation of distinct genus called Bifidobacterium presently composed

of over 30 species. Bifidobacteria are strictly anaerobic, non-spore

forming rods. They are among the more common LAB in the human

intestinal tract competing with Bacteroides species for predominance

in the colon. They constitute 95% of the gut bacterial population in

healthy, breast-fed infants.25 Bifidobacterium populations tend to

remain stable in the adult human intestine, but may decline with age;

the decline may even contribute to aging.26 Their numbers are

devastated by antibiotics and other environmental toxins. The

presence of Bifidobacterium within the intestinal tract is associated

with numerous health benefits.

The list of health benefits for probiotic Bifidobacterium is extensive.

Nutritionally, they all metabolize lactose, generate the L(+) form of

lactic acid, synthesize certain vitamins, ferment indigestible

carbohydrates, and produce beneficial short-chain fatty acids.

B. bifidum, B. breve, and B. lactis all exhibit protective effects against

acute diarrhea. B. longum and B. bifidum have been shown to reduce

the incidence and duration of antibiotic-associated diarrhea as well as

traveler’s diarrhea. They inhibit pathogens principally by the

production of organic acids and hydrogen peroxide and through

stimulation of the host immune system. Bifidobacterium species have

been found to relieve constipation, alleviate inflammatory bowel

disease, and reduce serum cholesterol levels. In animal models,

B. longum and B. breve have been shown to prevent DNA damage

which suggests probiotics may prevent or delay the onset of

certain cancers.25

Saccharomyces boulardii

S. boulardii, formally known as S. cervesiae variant boulardii Hansen

CBS 5926, is a non-colonizing, lactic acid producing yeast.11 It has

been widely used worldwide as a beneficial probiotic. Clinical trials

have shown that S. boulardii prevents or treats many intestinal

maladies including antibiotic-associated diarrhea, recurrent

Clostridium difficile-associated disorders, acute diarrhea, traveler’s

diarrhea, and diarrhea in tube-fed patients. In adults, S. boulardii has

been successfully used to treat AIDS-related diarrhea and to prevent

relapses of Crohn’s disease and ulcerative colitis. S. boulardii exerts

direct protective effects against the enteric pathogens Vibrio cholerae

and E. coli. It is known to exert several beneficial effects on the host

gastrointestinal tract through diverse mechanisms of action. In vivo,

S. boulardii secretes proteases and other substances that break down

bacterial enterotoxins and inhibit their binding to intestinal receptors.

S. boulardii stimulates host immune defenses, reduces intestinal

secretions, inhibits enterotoxin-induced inflammatory responses and

enhances production of intestinal trophic factors such as brush border

membrane enzymes and nutrient transporters.

Streptococcus thermophilus and Lactobacillus bulgaricus

These two species of LAB are the primary cultures used in yogurt

production.27While both species are transient and do not colonize the

intestinal tract, they have significant health benefits. They metabolize

lactose, improving lactose intolerance. In vitro studies have shown that

these two species have potent antimicrobial activities against

Pseudomonas, E. coli, Staph. aureus, Salmonella, and Shigella. In some

cases, this antimicrobial activity was compared to that of L. acidophilus

and found to be stronger. L. bulgaricus has also shown in vitro activity

against H. pylori. These two yogurt culture bacteria have been used for

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millennia to promote health and longevity and will, without doubt,

have a continuing vital role as probiotic supplements.

Enterococcus faecium

E. faecium, formerly called Streptococcus faecium, is a ubiquitous

organism found in a variety of foods as well as in soil and on plants.

It colonizes the skin, intestinal tract, and genitals in humans. E. faecium

is a hearty species capable of surviving higher temperatures and lower

pHs than other probiotics. Several studies have suggested E. faecium

effectively prevents and resolves antibiotic-associated diarrhea and it

has been used to treat acute gastroenteritis. In vivo and in vitro studies

have demonstrated an inhibiting effect against several pathogenic

organisms including Staph. aureus, E. coli, Salmonella, Clostridium, and

Listeria.28 No longer a nonpathogenic commensal bacterium,

E. faecium has increasingly become capable of causing severe, often

life-threatening infections.7 The acquisition of antibiotic resistance by

enterococcal species is a growing clinical problem. At present about

one-half of E. faecium clinical isolates are resistant to the critically

important antibiotic vancomycin.29 The risks of E. faecium use as a

probiotic are rapidly becoming greater than the potential benefits.

PROBIOTICS - Health Benefits

Probiotic organisms have been shown to be effective in a variety of

both gastrointestinal and extra-intestinal conditions beyond modulating

intestinal microflora and replenishing and maintaining normal gut

commensal bacterial equipoise.

Diarrhea

The benefits of probiotics have been clearly documented in four types

of diarrhea: antibiotic-associated diarrhea, Clostridium difficileassociated

diarrhea (CDAD), rotavirus diarrhea, and infectious

diarrhea.1,30-32 Antibiotic-associated diarrhea and CDAD are the best

documented conditions that may be prevented or treated with

probiotics.12,33 A meta-analysis of 25 randomized, controlled trials

involving 2,810 patients concluded that probiotics significantly

reduced the relative risk of antibiotic-associated diarrhea by 57%.12

Three types of probiotics were found to be most beneficial: S. boulardii,

L. rhamnosus GG, and multispecies probiotic combinations. A

meta-analysis of 23 randomized, controlled trials conducted by the

United Kingdom West Midlands Health Technology Assessment

Group found that probiotics significantly reduced the relative risk of

CDAD by 46%.34 S. boulardii has been consistently found to reduce the

risk of new and recurrent cases of CDAD. S. boulardii has been found

to be particularly beneficial for adults who have suffered more than

one bout of recurrent CDAD.35,36 Rotavirus-induced diarrhea, a

common problem in hospitalized children, has been shown to be

prevented by L. rhamnosus, L. casei, S. thermophilus, and B. bifidum.6

L. rhamnosus, L. reuteri, L. casei, and S. boulardii have been found to

either effectively prevent or treat community-acquired infectious

diarrhea in infants and children.1

Vaginal dysbiosis

Dysbiosis refers to the disruption of the normal microbial ecosystems

in body tissues that may lead to clinical symptoms and disease. As in

the intestinal tract, the normal vaginal microflora can be disrupted and

undesirable microorganisms can proliferate especially during and

following courses of antibiotics. Historically, preparations of LAB,

introduced either as yogurt soaked tampons or douches or

encapsulated probiotic suppositories, have been used to check the

growth of pathogens with favorable clinical results. Unfortunately,

studies on the efficacy of probiotics for vaginal infections often have

mixed results, probably due to differences in study design, selection of

proper probiotic strains, probiotic viability, and other factors.

However, clinicians and patients alike have typically found that vaginal

infections commonly recur when drugs alone are prescribed, while

better outcomes are achieved when probiotics are applied vaginally

concomitantly with medications.32,37 Direct vaginal application may

not be necessary as studies show that orally administered probiotics

can reduce the incidence of recurrent yeast vaginitis, bacterial

vaginosis, and urinary tract infections.38

Antagonism to pathogens

The use of probiotics for both intestinal and vaginal disorders hinges

on the ability of specific strains to antagonize the growth of diseasecausing

organisms. In the intestinal tract, a delicate balance constantly

needs to be maintained between beneficial and pathogenic organisms.

A variety of factors can shift the intestinal microflora balance in favor

of pathogens. These factors include antibiotics, immunosuppressants,

stress, aging, poor diet, excessive alcohol intake, environmental

pollutants, and infections. Many studies have confirmed that

probiotics promote a more favorable balance of intestinal microflora

by reducing populations of harmful microorganisms. Probiotics

accomplish this task primarily by producing substances toxic to

pathogenic organisms such as lactic acid, acetic acid, formic acid,

hydrogen peroxide, and bacteriocins.15 Probiotic bacteria also compete

with pathogens for nutrients and living space in the gut. Bifidobacteria

are capable of absorbing large quantities of ferrous iron, depriving

pathogens of iron and inhibiting their growth. Clinically, the

re-establishment of a favorable bowel microflora balance in the gut

may manifest short-term as a resolution of diarrhea or other

gastrointestinal symptoms. Long-term, a re-established healthy

balance may reduce the risk of a variety of chronic degenerative or

immunologically-mediated diseases.17,39

Immune function enhancement

The intestines are the primary immune organ in the body. The

bowel-associated immune system contains the largest mass of

lymphoid tissue in the human body, a vitally important component of

total host immunologic capacity.40 Bowel mucosa and lymphoid tissue

are closely linked immunologically with gastrointestinal microflora.

Substantial evidence associates probiotic bacteria with modulation of

host-mediated immune responses. Probiotic bacteria boost both

innate and acquired immune responses. These include increases in

circulating lymphocytes, stimulation of phagocytosis and antigenspecific

antibody secretion, and increased production of interferon-g

and other cytokines. Immunologic enhancement properties are best

documented for L. casei, L. rhamnosus, L. plantarum, L. bulgaricus,

L. acidophilus, B. bifidum, and B. breve.While these species are almost

certainly not the only probiotics that modulate immune function, they

should definitely be part of any therapeutic probiotic regimen to

support the immune system.40-42

Digestive support

Most lactic acid probiotic bacteria are capable of metabolizing a variety

of carbohydrates, including lactose. LAB metabolism of lactose is what

enables many lactose-intolerant people to consume yogurt, but not

other dairy products. LAB ferment carbohydrates into other shortand

medium-chain organic acids in addition to lactic acid. Some LAB

species also secrete proteolytic and lipolytic enzymes that facilitate

digestion of proteins and fats. People who produce inadequate

amounts of stomach acid and cannot activate the proteolytic enzyme

pepsin and individuals with pancreatic insufficiency deficient in

pancreatic proteases and lipases all benefit from dietary

supplementation with probiotics. Enhanced protein digestion often

benefits people with allergies due to increased gut permeability defects

by reducing the ability of large proteins to cross the intestinal barrier,

enter the bloodstream, and trigger immune responses.42,43

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Short-chain fatty acid production

Probiotics especially the bifidobacteria, are able to break down and

metabolize non-digestible carbohydrates such as fiber. The major

by-products of this process are short-chain fatty acids (SCFA) such as

lactate, acetate, propionate, and butyrate. SCFA lower intestinal pH

and create an environment inhospitable to pathogenic bacteria such as

E. coli and Salmonella species. SCFA nourish colonic mucosal cells

supplying 60-70% of colonocyte energy needs. Butyrate is the

preferred energy source for colonocytes. Studies in animals and

humans have found SCFA directly stimulate colonic calcium,

magnesium, and potassium absorption, increase colonic blood flow,

enhance tissue oxygenation and transport of nutrients, and may be of

therapeutic value for various intestinal disorders.45,46

Enhancement of mineral bioavailability

Mineral absorption requires an acidic medium, especially when the

minerals are in the form of inorganic salts. Stomach acid is usually

sufficient to dissolve mineral salts, but when stomach acid is inadequate

mineral salts may not fully dissociate. LAB aid mineral absorption via the

production of acidic microenvironments adjacent to the intestinal lining

and by generating SCFA that donate protons necessary for mineral

absorption.Animal studies have demonstrated that LAB, especially in the

presence of a probiotic growth factor like inulin, increase intestinal

absorption of calcium, magnesium, potassium and zinc.46,47

Vitamin production

LAB produce small amounts of certain B vitamins, including folates and

vitamin B12.48Microbial synthesis of vitamin K in the intestine appears to

have nutritional significance in most animal species. Bifidobacteria,

streptococci, and enterococci have been shown to produce vitamin K.49

Reduction of cholesterol

Studies have shown that some probiotics can lower total serum

cholesterol and low density lipoprotein cholesterol.50-52

In vitro studies have shown L. casei and L. acidophilus effectively

remove cholesterol from culture media. Researchers postulate that

LAB assimilate cholesterol in the gut or deconjugate bile acids

disrupting the intestines-to-liver circulation of cholesterol.

Management of inflammatory bowel disease

Inflammatory bowel disease refers to two chronic or relapsing diseases

of unknown cause: ulcerative colitis and Crohn's disease. Although

these two diseases have some features in common, there are important

differences. Ulcerative colitis is an inflammatory disease of the colon.

Often the rectum is most severely involved. The colonic mucosa

becomes inflamed and develops ulcers. Patients experience diarrhea

frequently with blood and mucous in the stool. Crohn's disease most

commonly affects the last part of the small intestine (terminal ileum)

and parts of the large intestine. However, Crohn's disease can attack

any part of the digestive tract. The inflammation of Crohn's disease

can extend deeply into the intestinal wall and generally tends to involve

the entire bowel wall, whereas ulcerative colitis affects only the bowel

lining. Pouchitis is a complication of surgical therapy for ulcerative

colitis in which the entire colon has been removed and a pouch made

from the ileum has been connected to the anus. Pouchitis refers to

inflammation of this pouch. Evidence suggests that inflammatory

bowel disease may result from abnormal activation of the mucosal

immune system against enteric flora triggering inflammatory

mediators.1 L. casei and L. lactis have been shown to successfully treat

IBD by increasing the gut IgA immune response.53 A mixture of

B. longum, inulin, and oligofructose reduced inflammatory cytokines

and colon inflammation in patients with ulcerative colitis.54 Daily

intake of L. rhamnosus alone or intake of a proprietary combination of

L. casei, L. plantarum, L. acidophilus, L. bulgaricus,

B. longum, B. breve, B. infantis and S. thermophilus (VSL) in patients

with pouchitis can provide significant clinical benefit and delay the

first onset of pouchitis in patients without symptoms.55 S. boulardii

has been shown to prolong remission and reduce relapses in patients

with Crohn’s disease.56 There is considerable interest in the use of

probiotics for inflammatory bowel disease among gastroenterologists.

Amelioration of food allergy

The ability of probiotics to reduce the symptoms of food allergy was

noted over 20 years ago.57,58 Since then, several well-designed studies

have indicated that supplementation with specific probiotic strains are

effective for atopic disorders. In infants with atopic eczema and cow’s

milk allergy, a whey formula supplemented with L. rhamnosus GG was

shown to significantly improve clinical symptoms and markers of

intestinal inflammation.18 In children with atopic dermatitis, a

combination of L. rhamnosus and L. reuteri proved beneficial.59

Consumption of these select Lactobacillus probiotics downregulates

over-expressed immune responses.

Alleviation of irritable bowel syndrome

Irritable bowel syndrome is a common multifactorial gastrointestinal

disorder characterized by flatulence, diarrhea, constipation, and

abdominal discomfort and pain. Although challenging to study

because of the heterogeneous patient populations, clinical trials with

the individual strains B. infantis60 and L. plantarum61 found that these

probiotics effectively reduced irritable bowel syndrome symptoms

such as abdominal pain and discomfort, bloating and distention,

bowel movement difficulty, and flatulence. In a small pilot study of

patients with irritable bowel syndrome, a food elimination diet

followed by treatment with a multispecies probiotic preparation

(Vital-10® powder) containing B. bifidum, B. infantis, L. acidophilus,

L. rhamnosus, L. plantarum, L. salvarius, L. bulgaricus, L. casei, L. brevis,

and S. thermophilus improved pain, stool frequency, and quality of life

scores.62 The efficacy of multispecies preparations for irritable bowel

syndrome was confirmed by a double-blind, placebo-controlled trial

that found a combination of two strains of L. rhamnosus, B. breve, and

Propionibacterium freudenreichii spp. shermanii reduced symptoms of

pain, distension, flatulence, and abdominal gurgling sounds

(borborygmi) by over 40%.63

Anti-carcinogenic activity

There is increasing evidence that probiotics have anti-mutagenic and

anti-carcinogenic activities in the colon.64 Probiotics have been shown

to inhibit aberrant crypt (precancerous lesions) formation and tumors

in animal models.65 Probiotic bacteria may exert anti-carcinogenic

effects through a variety of mechanisms. LAB produce organic acids

lowering intestinal pH which is strongly associated with a lower

incidence of colon cancer.66 LAB are able to bind and breakdown

dietary mutagenic compounds thereby reducing host exposure.

Probiotics may mediate tumor suppression through stimulation of the

host immunoprotective response. Probiotic bacteria enhance cytokine

production (interferon-g, interleukin-1b, tumor necrosis factor-a),

macrophage and lymphocyte activation, T- and B-cell proliferation,

and antibody production.66 Evidence for anti-tumor activity of LAB

has been reported in studies using pre-implanted tumor cells in animal

models. Feeding cultures of LAB to mice has also been shown to

inhibit the growth of injected tumor cells.66

PROBIOTICS - Frequently Asked Questions

How do I know I need probiotics?

Probiotics may be used to maintain a healthy, balanced intestinal

microflora. Modern diets consisting of highly processed, sterilized

foods are deficient in essential microorganisms such as L. plantarum,

L. rhamnosus, L. casei, and L. acidophilus.67 These organisms must be

consumed to maintain their needed presence in the gastrointestinal

Page 5

tract. Infants born by cesarean section and formula-fed infants have

disordered intestinal microflora that may have short- and long-term

adverse health consequences and may benefit from probiotics.68,69

Aging is associated with microflora alterations especially a decrease in

the numbers of bifidobacteria.26 Probiotics may reverse age-associated

changes in intestinal microbial balance. Probiotics may be taken along

with antibiotics, immunosuppressants or other drugs that disrupt the

microflora equilibrium. Symptoms that have been extensively studied

and shown to be improved by probiotics include antibiotic-associated

diarrhea and other types of diarrhea, vaginitis, lactose intolerance,

intestinal and vaginal dysbiosis, abdominal distention, flatulence, and

constipation. Some probiotics have also been shown to alleviate food

allergies and modulate the immune system. When symptoms are

present, the need for probiotics is best determined in consultation with

a health practitioner experienced in their use.

What probiotics do I take?

Consulting a knowledgeable health practitioner experienced in the use

of probiotics is the optimal approach to determine which probiotics

may be of most benefit. The appropriate choice of probiotic may be

guided by clinical reports and research published in the medical

literature. For example, L. acidophilus, L. bulgaricus, B. longum, and

S. thermophilus have been shown to reduce the risk of diarrhea

induced by the antibiotics.12 At least six rigorous clinical trials have

shown that S. boulardii substantially decreases the risk of antibioticinduced

diarrhea and protects against C. difficile.12 Rotavirus

gastroenteritis in children can be prevented by L. rhamnosus, L. casei,

S. thermophilus and B. bifidum.6 L. rhamnosus has been shown to

effectively reduce the symptoms of food allergies.18,59 H. pylori, an

organism associated with peptic ulcer disease, is antagonized by a

number of lactobacilli including L. casei, L. delbrueckii, L. helveticus,

and L. acidophilus, as well as by Bifidobacterium.70,71 For people with

irritable bowel syndrome or inflammatory bowel disease a

combination of lactobacilli and bifidobacteria appears to offer the

most benefit.1,31 People desiring to favorably alter their intestinal

microflora are best served by a broad combination of Lactobacillus and

Bifidobacterium species.

How will I know if probiotics have helped me?

If symptoms are present, a reduction or resolution of symptoms is the

best indication probiotics have helped. Symptoms may take days or

even weeks to improve depending on the individual’s response to the

probiotics and the severity of the underlying condition. If probiotics

are used in the absence of symptoms as a general health measure to

restore a balanced intestinal microflora, then it may not be apparent

that probiotics are helping.

Are there any side-effects from probiotics?

Uncommonly people may experience a worsening of their clinical

symptoms following the initiation of probiotics. This is attributed by

some practitioners to a “die-off” effect as pathogenic bacteria die

releasing toxic cell products. The exact mechanism for a transient

worsening in symptoms is unknown, but it does occur. Persistence in

taking the probiotics is usually rewarded by an improvement in

symptoms. Some individuals may experience gas, abdominal

discomfort, and even diarrhea that usually resolve with time. Rarely,

probiotics have been associated with opportunistic infections.

Are there tests that can assess my response to probiotics?

With certain exceptions, such as the presence of C. difficile toxin or

pathogenic microorganisms in the stool, there are no readily available,

reliable clinical laboratory tests that can assess a response to probiotics.

Many practitioners order stool cultures on the premise that probiotic

content in the intestinal tract is reflected in stool count.However, most

probiotics are fastidious and not easily cultured from routine stool

samples. Intestinal biopsy and DNA amplification techniques are used

currently to demonstrate probiotic colonization of the intestines. A

negative stool culture for probiotic species does not indicate lack of

colonization, presence, or benefit.

Should I buy a probiotic containing prebiotics?

Prebiotics are carbohydrates that are indigestible by the human

intestine and selectively stimulate the activity and growth of certain

bacteria in the colon.Most prebiotics are non-digestible chains of 2 to

9 sugar molecules (oligosaccharides). They are commonly found in

chicory, asparagus, artichokes, onions, garlic, leeks, and soybeans as

well as in human breast milk and cow’s milk. Prebiotics have attracted

great attention as a way of increasing the number of healthy beneficial

commensal bacteria in the intestine. The most extensively used

prebiotics include lactulose, oligofructose, galactooligosaccharides,

soybean oligosaccharides, and chicory-derived inulin. Some prebiotics,

such as lactulose, are synthetic, whereas most other oligosaccharides

are natural food components.

After ingestion, prebiotics pass through the small intestine into the

colon where they are selectively utilized by the beneficial LAB

microorganisms.Numerous studies suggest bifidobacteria prefer short

chain oligosaccharides and recent studies suggest oligofructose,

soybean oligosaccharides and galactooligosaccharides are the most

bifidogenic.72,73 Prebiotics can significantly increase the numbers of

bifidobacteria in the colon and decrease the populations of pathogenic

bacteria such as clostridia, fusobacteria, and Gram-positive cocci.

Inulin is a commonly used prebiotic that is not usually associated with

the gas and bloating sometimes associated with other prebiotics. Inulin

is also more difficult for pathogens to metabolize and unlike some

highly processed, long chain fructooligosaccharides less likely to be

used as a food source by pathogenic bacteria. Probiotics combined

with prebiotics, termed synbiotics, are generally a good choice.

When and how should I take a probiotic?

People often receive contradictory answers to this question. Probiotic

labels from different manufacturers may directly contradict each other.

Some suggest that the probiotics be taken with meals whereas others

recommend between meals. Health professionals are also divided on

this topic. Advocates of ingesting probiotics with meals reason that

food buffers stomach acid thereby providing protection for the

microorganisms. Those who recommend taking probiotics without

food usually suggest consuming them with lots of water. The water

dilutes the stomach acid and may help move the organisms quickly

into the intestines minimizing exposure to acid and bile. Few studies

provide direct support for either approach. However, numerous

studies have administered probiotics with meals and documented

significant benefits. The most prudent approach is to consume

probiotics with moderate amounts of food no warmer than room

temperature.

If I am taking antibiotics, when should I take a probiotic?

In the past, people were often told not to take probiotics while on

antibiotics. The thinking was that the antibiotics would kill ingested

probiotics. The trouble with this approach is that it allowed pathogenic

microorganisms to proliferate unopposed by beneficial bacteria often

resulting in antibiotic-associated diarrhea and other problems.

Probiotics should be taken while on antibiotics. The probiotics should

be taken at least 1 hour before or 2 hours after ingestion of antibiotics.

How much probiotic do I take?

The answer depends on whether the probiotics are being used for

therapeutic reasons or simply to maintain a healthy intestinal

microflora balance. In general, a dose of 1 billion colony forming units

(CFUs) is required to deliver significant numbers of viable probiotics

to the intestines. There is a trend toward using higher doses. The

proprietary probiotic blend VSL#3 comes in packets each containing

450 billion organisms and has been used safely in patients with

inflammatory bowel disease.Doses as high as 200 billion CFUs per day

have been safe and well-tolerated in patients following liver

transplantation. A clinical research study involving the administration

of 200 billion organisms daily of a Klaire Labs proprietary blend of 6

probiotic species to kidney transplant patients has been approved by

the Western Institutional Review Board and is ongoing.

Do probiotic organisms survive exposure to stomach acid

and bile?

Different probiotic organisms have differing sensitivities to stomach

acid and bile. S. boulardii is not affected by gastric acid. LAB are more

sensitive and do not thrive in an excessively acidic or alkaline medium.

Some LAB, such as L. rhamnosus, are more sensitive than others.

Probiotic manufacturers have devised a number of methods to

enhance probiotic survival after oral administration. Some

manufacturers offer enteric coatings for the probiotics composed of

cellulose or, in many cases, synthetic plasticized polymers. Many

individuals with environmental sensitivities cannot tolerate the

plasticized polymers. One manufacturer has developed an innovative

process that coats probiotic microorganisms with vegetable-derived

fatty acids. This micro-encapsulation not only shields the probiotics

from stomach acid, it protects them from air and moisture and keeps

them viable at room temperature. Klaire Labs makes use of a highly

purified marine plant extract in an acid-stable technology. The extract

is mixed with the probiotics.When exposed to stomach acid it forms a

gel-like matrix surrounding the microorganisms protecting them from

gastric acid. When delivery of probiotics to the oropharynx,

esophagus, and stomach is desirable, probiotics without a gastric acid

protective delivery system should be selected.

Do probiotics have to adhere to the intestinal tract to provide

a benefit?

Adherence to the intestinal mucosal lining is just one characteristic

among many that may, or may not, make an organism useful as a

probiotic. Adherence is a property observed under laboratory

conditions. There is evidence that normal intestinal microflora do not

adhere to intestinal epithelial cells, but live suspended in the intestinal

contents.74 Adherence is certainly not necessary for a probiotic to

provide benefit. There are numerous scientific and anecdotal reports

about the therapeutic benefits of yogurt, yet the primary bacteria

found in yogurt cultures, S. thermophilus and L. bulgaricus, are

transient microorganisms and do not adhere to the mucosa.

Modulation of immune function is a probiotic benefit that clearly does

not require mucosal adherence or intestinal colonization. Probiotics

are readily taken up by the specialized lymphoid nodules in the walls

of the small intestines called Peyer’s patches stimulating the

production of IgA, cytokines, and other mediators of immune

function. Even the administration of dead probiotics has been shown

to enhance immune function.75

Intestinal mucosal colonization has only been demonstrated in vivo for

a few probiotic strains. L. rhamnosus GG persisted in cultures from

rectal biopsies for up to 12 days after oral administration.76 Stool

culture sensitivity was quite poor even though samples were

immediately processed. In one subgroup, L. rhamnosus was found in

only 20% of final stool cultures compared to 88% of rectal biopsy

cultures. In a second study, probiotics were shown to be recoverable

from rectal biopsies when dispensed orally to critically ill patients

receiving powerful antibiotics.77 L. plantarum supplementation

reduced the populations of pathogenic Enterobacteriaceae and sulfite

reducing clostridia. In vivo studies of probiotic intestinal colonization

make two very important points. The first is that routine stool cultures

have a very limited use, if any, in assessing probiotic therapy. The

second is that sustained consumption of probiotics is required to

maintain colonization and benefit.

Is freeze-drying of probiotics harmful?

Freeze-drying, or lyopholization, is not harmful to probiotics when

done according to strict guidelines. It is an accepted practice that helps

ensure long-term probiotic microbial viability. Routine survival

studies ensure the probiotics remain viable following freeze-drying.

Probiotics that are not freeze-dried, such as liquid probiotics, have a

much shorter shelf life even when refrigerated. The short shelf life is

due to eventual toxicity of fermentation end-products to the

microorganisms. A well-known example is the die-off of yeast that

occurs over time during the fermentation of beer and wine. Freezedrying

halts fermentation thereby enhancing microbial viability.

Do all probiotics need to be refrigerated?

In general, it is highly recommended that probiotics be refrigerated to

maximally preserve their viability over time. Probiotics that have been

microencapsulated with fatty acids are the only exception and do not

need to be refrigerated. Probiotics sold in retail stores are often not

refrigerated. Consequently, industry and consumer studies have found

that 30 to 50% of probiotic products available in retail stores contain

significantly less viable microorganisms than claimed on their labels.

Although most probiotics should be refrigerated, they do not spoil or

die-off quickly at room temperature. They may be left at room

Page 6

temperature for days and even weeks without a great loss of viable

organisms. They should not be subjected to high temperatures for

prolonged periods of time. The graphs illustrate microbial viability for

selected probiotic strains over time at 4°C (39°F), 23°C (73°F) and

30°C (86°F) and show that survival is better at low temperatures than

high temperatures. At room temperature (23°C), colony counts begin

diminishing after one to two months explaining why so many overthe-

counter retail probiotic products do not contain the labeled

amounts of viable probiotics. The charts also show that certain strains,

such as L. rhamnosus, are more temperature-vulnerable than others.

However, leaving probiotics out at room temperature or even warm

temperatures for a few hours or even a few days will only result in small

losses of organisms. Although probiotics should be shipped with cold

packs, there is no cause for concern or worry if the cold pack has

melted by the time of delivery.

Does it matter if probiotics come in plastic or glass bottles?

Probiotics are usually anaerobic organisms, meaning they live in the

absence of oxygen. Exposure to air is undesirable and even toxic.

Exposure to moisture is potentially more detrimental to freeze-dried

probiotics than air. Some people argue that probiotics should be

packaged in glass bottles to minimize exposure to air and moisture.

However, the difference in permeability between glass and

high-density polyethylene (HDPE), a plastic commonly used for

bottling, is negligible. Furthermore, once the container has been

opened, air and moisture enter the bottle and the relative permeability

of glass and HDPE becomes irrelevant. The placement of desiccants

inside probiotic containers is a good way to minimize moisture inside

the container be it glass or plastic. Bottling probiotics in glass or HDPE

containers is equally acceptable.

Is it beneficial to have the supernatant included in

the probiotic?

Supernatant is culture medium transformed by the bacteria as they

multiply adding a variety of substances to the original medium. Milk is

an example of a culture medium; yogurt is an example of a supernatant.

At least one company claims that including the supernatant with the

bacteria provides additional health properties. Additional benefit to the

supernatant is possible, although the evidence is scant. Maintaining the

supernatant during production could be detrimental to probiotic

survival. The by-products of fermentation may be toxic to the probiotics.

The hypothetical benefits of including supernatant seem to be

outweighed by the negative impact on probiotic viability.

Can probiotics be used for infants?

Probiotics have been used safely and with benefit in infants. A

newborn’s intestinal tract is sterile and does not harbor

microorganisms. Microbial colonization begins at birth. During the

first week of life, Streptococcus, Clostridium, Bifidobacterium, and

Lactobacillus all vie for predominance. By the end of the first week,

bifidobacteria are usually established as the predominant bacteria.

Breast-fed infants typically have much higher numbers of

bifidobacteria in their intestinal tracts than do formula-fed infants

who have higher levels of E. coli and other pathogenic coliform

bacteria. This is due in part to the presence of bifidogenic substances

in breast milk.

Although the newborn intestinal tract is quickly colonized, it is not

fully developed. Infants are unable to metabolize a form (isomer) of

lactic acid known as D(-). Exposure to D(-)-lactic acid could

theoretically lead to D(-)-lactic acidosis, a serious condition.78 Some

have advocated that probiotic formulations intended for infants

should not include D(-)-lactic acid producing organisms such as

L. acidophilus, L. brevis, L. plantarum, or L. bulgaricus. However, there

are no reports of D(-)-lactic acidosis in infants due to probiotics and

D(-)-lactic acid producing probiotics have been used safely in infants.

Clinical trials have demonstrated the benefits and safety of probiotics

in infants. In one controlled trial, infants age 3 to 24 months, received

an average of 41 million or 3.7 million CFU each of B. lactis and

S. thermophilus per kilogram each day in a standard milk-based

formula for an average of seven months. The probiotics were well

tolerated and the infants receiving probiotics had adequate growth, less

colic or irritability, and a lower frequency of antibiotic use.79 In

another study, 190 million CFU B. bifidum and 14 million CFU

S. thermophilus per gram of formula reduced the incidence of acute

diarrhea and rotavirus shedding during hospital stays.80 Two studies

have found probiotic supplementation significantly improves infants

with atopic eczema.18,19 A low dose of 60 million CFU L. rhamnosus

GG did not decrease the incidence of necrotizing enterocolitis in

preterm infants with a gestational age less than 33 weeks.81 However, a

proprietary probiotic formulation containing 10 billion CFU of

L. acidophilus and B. infantis per capsule administered with breast milk

significantly reduced the incidence and severity of necrotizing

enterocolitis in very low birth weight infants.82

CONCLUSION

Probiotics have been used by people for millennia since the time

humans first consumed fermented milk products. Probiotics can be

essential for the normal digestive, endocrine and immunological

functions of the bowel. They inhibit pathogenic microorganisms and

have been used therapeutically to treat a variety of gastrointestinal and

even systemic disorders. Probiotics transiently colonize the bowel and,

except when used to treat an acute disorder, must be regularly

consumed to maintain benefit. Selection of appropriate probiotics,

alone and in combination, is best done in consultation with an

experienced, knowledgeable health practitioner.

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