pro biotics

1

MMIICCHHAAEELL

CCHH

“To … hell… with… yogurt.”

Chas Addams - The Half-Baked Cookbook. Simon and Schuster, New York, NY 2005

HHIIKKIINNDDAASS

The Bulgarian farmer's longevity and healthy life are the result of the consumption of fermented dairy products.

E. Metchnikoff

Published Definition Reference

Substances produced by microorganisms which promote the growth of other microorganisms

Lilly and Stillwell 1965

Organisms and substances which contribute to intestinal microbial balance Parker 1974

A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance

Fuller 1989

Live microorganisms which when

Probiotics ‐ definitions

A viable mono- or mixed-culture of microorganisms which applied to animal or man, beneficially affects the host by improving the properties of the indigenous microcflora

Havenaar and Huis In’t Veld 1992

Living microorganisms, which upon ingestion in certain numbers, exert health benefits beyond inherent basic nutrition

Schaafsma 1996

A microbial dietary adjuvant that beneficially affects the host physiology by modulating mucosal and systemic immunity, as well as improving nutritional and microbial balance in the intestinal tract

Naidu et al. 1999

A preparation of or a product containing viable, defined microorganisms in sufficient numbers, which alter the microflora (by implantation or colonization) in a compartment of the host and by that exert beneficial health effects in this host

Schrezenmeir and de Vrese 2001

Live microorganisms which when administered in adequate amounts confer a health benefit on the host.

FAO/WHO report, October 2001

Live microorganisms which when administered in adequate amounts confer a health benefit on the host.

2

Probiotic Market• Global market is currently valued at $22.6 billion and

projected to reach $28.8 billion in 2015• Target consumers are mainly located in Japan, Europe and

USA• Between 2003 and 2005, US probiotic market grew by 8.7% to

$5bn– 5% growth until 2013

• Growth factors include:– Consumer understanding of the effect of nutrition on health

– Rising healthcare costs

Source: Tallon 2009; “Global Probiotic Market to Grow – Analyst.” FLEXNEWS. 27 Sept 2010. Web. 27 Sept 2010.

• Dairy dominate the market• Beverages and snacks grow in size

US Probiotic Products

Probiotic products launched in United States, by category (2000‐2010)

14

16

18

s

Source: Mintel GNPD 22 Jan 2011

0

2

4

6

8

10

12

14

2000 2003 2004 2005 2006 2007 2008 2009 2010Year

Num

ber o

f Pro

duct

s

Dairy Non-Alcoholic Beverages Snacks Other

Human probiotics

G i i l bi i

Human probiotics can be grouped according to the ecological niches of the human body they occupy (or the part of the body they deliver their health‐promoting action to), such as:

• Gastro‐intestinal probiotics• Skin probiotics• Scalp probiotics• Probiotics of the oral cavity• Probiotics of the underarm and feet• Urogenital (including vaginal) probiotics

3

• Lb. acidophilus• Lb. amylovorus• Lb. brevis• Lb. casei• Lb. casei ssp. rhamnosus• Lb. crispatus

• Bf. adolescentis• Bf. animalis• Bf. bifidum• Bf. breve• Bf. infantis• Bf lactis

Probiotics Species

Bacillus cereusClostridium botyricumEnterococcus faecalisEnterococcus faeciumEscherichia coliLactococcus lactis ssp

Lactobacillus species

Bifidobacteriumspecies Other species

• Lb. delbrueckii ssp. bulgaricus

• Lb. fermentum• Lb. gasseri• Lb. helveticus• Lb. johnsonii• Lb. lactis• Lb. paracasei• Lb. plantarum• Lb. reuteri

• Bf. lactis• Bf. longum

Lactococcus lactis ssp. cremorisLactococcus lactis ssp. lactisLeuconostoc mesenteroides ssp. dextranicumPediococcus acidilacticiPropionibacterium freudenreichiiSaccharomyces boulardiiStreptococcus salivarius ssp. thermophilus

Cited by W.H. Holzapfel and U. Schillinger, Introduction to pre- and probiotics, Food Research International 35 (2002), pp. 109–16

Disorders Strains Clinical outcomes

Diarrhea caused by pathogenic bacteria and viruses

Lb. rhamnosus GG, Lb. casei Bf. lactis BB-12, Bf. bifidum Sc. thermophilus

Prevention and treatment of acute diarrhea caused by rotaviruses in children

Helicobacter pylori infection and complications Lb. johnsonii La1, Lb. salivarius, Lb. acidophilusLB

Inhibition of the pathogen growth and decrease urease enzyme activity necessary for the pathogen to remain in the acidic environment of the stomach

Inflammatory diseases and bowel syndromes Lb. rhamnosus GG Remediation in inflammatory conditions through modulation of the gastrointestinal microflora

Cancer in gastrointestinal tractLb. rhamnosus GG, Lb. rhamnosus LC-705, Lb. casei Shirota, Lb. acidophilus LA-2, Bifidobacterium sp., Propionibacterium sp.

Prevention or delay of the onset of certain cancers

Lb i Shi t Lb h HN001 Lb

Examples of probiotic strains used in prevention and treatment of some diseases

Mucosal immunity Lb. casei Shirota, Lb. rhamnosus HN001, Lb. acidophilus HN017, Bf. Lactis HN019 Enhancement of immune parameters

Allergic symptoms Lb. rhamnosus GG, Bf. lactis BB-12 Prevention of allergic diseases onset

Cardiovascular disease Lactobacillus sp. Prevention and therapy of ischemic heart syndromes

Bacterial and yeast vaginitis Lb. acidophilus, Lb. rhamnosus GG Eradication of vaginitis through restoration of dominated vaginal flora

Urinary tract infections Lactobacillus GR-1, Lactobacillus B-54, Lactobacillus RC-14

Lower risk of urinary tract infections through restoration of dominated vaginal flora

Strains OriginLactobacillus casei Shirota Yakult, JapanLactobacillus crispatus CTV05 Gynelogix, USALactobacillus reuteri MM53 BioGaia, SwedenLactobacillus casei F19 Arla Foods, Denmark/SwedenBifidobacterium lactis HN019 Danisco, FranceLactobacillus rhamnosus GG Valio, FinlandPropionibacterium freudenreichii ssp. shermanii JSLactobacillus acidophilus NCFM Rhodia, USALactobacillus acidophilus NCFB 1748Lactobacillus johnsonii LA1 (NCC 533) Nestlé Switzerland

Probiotic lactic acid bacteria marketed worldwide

Lactobacillus johnsonii LA1 (NCC 533) Nestlé, SwitzerlandLactobacillus acidophilus LA10 (NCC 90)Lactobacillus fermentum RC-14 Urex, CanadaLactobacillus rhamnosus GR-1Lactobacillus casei DN-114 001 Danone, FranceBifidobacterium animalis DN-173 010Lactobacillus plantarum 299v Probi AB, SwedenLactobacillus rhamnosus 271Lactobacillus casei CRL 431 Chr. Hansen, USABifidobacterium lactis BB-12Lactobacillus acidophilus LA-5Lactobacillus bulgaricus LBY27Streptococcus thermophilus STY-31

Adapted from FAO/WHO 2001

4

Human probiotics

G i i l bi i

Human probiotics can be grouped according to the ecological niches of the human body they occupy (or the part of the body they deliver their health-promoting action to), such as:

Gastro‐intestinal probiotics


Probiotic Products

• Dairy foods– Beverages, yogurt, kefir, ice cream, cheese

• Non‐dairy foods– Beverages, bars, chocolate, cereal, pizza, g pcondiments

• Dietary supplements– Infant formula, drops, tablets, capsules, powders

• Clinical therapeutics and health supporting/promoting formulations

Non‐Dairy BeveragesProduct Company Type Strain Dose Claim

GoodBelly NextFoods Juice Drink

Lactobacillus plantarum 299v, Bifidobacterium lactis Bi-07 (Probi)

20 bn per 300ml*

Clinically proven to promote healthy digestion and support natural immunity

Bravo Skane- 100% Lactobacillus plantarum HEAL9, Lactobacillus 4bn per Helps the body’s

Friscus mejerier%

Juice paracasei 8700:2 (Probi)p

1Lp y

natural defenses

ProViva Female Danone Juice

DrinkLactobacillus plantarum 299v (Probi)

Not provided

Helps body to increase iron uptake by about 50%

Gefilus Valio Juice Lactobacillus rhamnosus GG (Valio)

50 bn per 1L

Enhances natural defenses

Naked Probiotic PepsiCo Juice Bifidobacterium lactis

HN0195 bn per 300ml

Help promote healthy digestive and immune system

5

Swedes first with non‐dairy probiotic "little bottle”

ww

w.new

-nutrition.com/new

spage/030403a.ht

• Skane’s ProViva probiotic fruit arrived in the Swedish marketplace in 1994, containing Lactobacillus plantarum 299v (Probi).

•2003 marked approval of its health claims— the first given to a probiotic product marketed in Europe — enabled Skane

m

to market ProViva on its ability to calm an unsettled stomach by reducing the formation of gas.

•Pro Viva Shot! is an 80 ml juice drink which delivers 250 million bacteria (more than Proviva). The brand is an extension of Skånemejerier’s highly successful Pro Viva probiotic juice which in 2001 sold some 15 million liters in Sweden – a country of just 8 million people.

http://www.functionalingredientsmag.com

The first probiotic juice was launched in the fall of 2007 by Next Foods, founded by Steve Demos (who also founded Silk soy milk). GoodBelly is an

http://goodbelly.com/

organic fruit juice‐based probiotic beverage that contains a patented probiotic called Lactobacillus plantarum 299v, which was developed in the U.K. and has tested well for its effects on Irritable Bowel Syndrome. Twenty billion live bacteria are in each serving juices to provide digestive health. Three flavors include: Brilliant Blueberry, Peach Mango and Strawberry Rosehip. CLAIM: “GoodBelly is specifically designed to be enjoyed daily in order to boost your immune system and improve digestive health by replenishing your body’s healthy microflora. GoodBelly’s patented Lp299v probiotic strain has been clinically proven in over 15 years of research.”

Tokyo (JCN) ‐ Japanese food conglomerate Kagome announced their launch of a lactic acid bacteria beverage series, Labre, on March 14, 2006

The new product, which contains Lactobacillus brevis subsp. coagulans (Labre), helps maintain health. It comes in three sizes: 130ml, 100ml and 80ml. Prices are 105 yen (90 cents) for a 130ml bottle and 170 yen ($1 45) for three 80ml packs The 100ml

Kagome aimed to generate 10 billion yen ($86 mil) from sales of the new beverage in the first year.

($1.45) for three 80ml packs. The 100ml bottle, which will be available via home delivery only, will be open‐priced.

6

Activia® is a great‐tasting lowfat yogurt from Dannon® that contains Bifidus Regularis™ a natural probiotic culture that can help regulate your digestive system by helping reduce long intestinal transit time.

Do I really want “it” to go faster?!

=

September 23, 2009Dannon settles class action suit over Activia health claimsDannon has reached a settlement in a class action lawsuit filed over misleading advertising on its Activia and DanActive lines of yogurt, according to the Associated Press. The health claims indicated that the yogurt's bacteria would help with digestion or with the immune system.

As part of the settlement the White Plains N Y company doesAs part of the settlement, the White Plains, N.Y. company does not admit any wrongdoing but will create a $35 million fund to reimburse qualified consumers up to $100 for products purchased.

http://www.csgrr.com/Dannon/

http://bx.businessweek.com

7

Human probiotics

G i i l bi i

Human probiotics can be grouped according to the ecological niches of the human body they occupy (or the part of the body they deliver their health‐promoting action to), such as:Probiotics of the oral cavity• Gastro‐intestinal probiotics• Skin probiotics• Scalp probiotics• Probiotics of the oral cavity• Probiotics of the underarm and feet• Urogenital (including vaginal) probiotics

When he was just a boy of 12, John Tagg contracted an especially bad case of strep throat that led to rheumatic fever. Rheumatic fever is a delayed, autoimmune reaction to the bacteria that causes strep throat – Streptococcus pyogenes. It is a very painful, inflammatory condition that makes joints swell and redden. Because rheumatic fever can permanently weaken and damage the heart, it is important to prevent a recurrence of strep John’s doctor put him on a course of

K12 story

important to prevent a recurrence of strep. John s doctor put him on a course of antibiotics every day for 10 years, a common procedure at the time.

This childhood experience inspired Professor Tagg to devote his life to the study of friendly probiotic bacteria that can prevent strep throat and other infections that enter through your mouth.

Today, more than 35 years later, Professor Tagg is a world renowned microbiologist from the University of Otago in New Zealand whose targeted research has led to the discovery of S. salivarius BLIS K12, a revolutionary ORAL probiotic that prevents infection (including strep throat) where it begins – in your mouth.

http://culturedcare.com/

BLIS K12 is a new, advanced probiotic discovered by Professor John Tagg from the Department of Microbiology and Immunology at the University of Otago in New Zealand.

BLIS stands for Bacteriocin‐Like‐Inhibitory‐Substance and is the naturally occurring component of certain strains of micro‐organisms

K12 story

http://www.springerlink.com/content/dg56pk5k48l6w5h1/fulltext.html

component of certain strains of micro‐organisms (probiotics) which control undesirable and disease‐causing bacteria. BLIS K12 is the special BLIS probiotic strain derived from the friendly bacteria S. salivarius.

It has been shown to safely control the bacteria that frequently causes strep throat, earache, upper respiratory infections, sinus infections and halitosis (bad breath).

http://culturedcare.com/

8

www.stenata.cz

Nisin: Howell et al. J. Clin. Periodontol. 1993. 20(5):335-9.Histatin-5: Paquette et al. J. Clin. Periodontol. 1997.24(4):216-22.

Human probiotics

G i i l bi i

Human probiotics can be grouped according to the ecological niches of the human body they occupy (or the part of the body they deliver their health‐promoting action to), such as:


Urogenital probiotics

Bacterial vaginosis• Lactobacillus is replaced by several pathogenic bacteria

of which Gardnerella vaginalis is most prevalent1. • Associated with premature labor, premature rupture of

membranes and low birth weight2, higher risk of acquisition of HIV3 and herpes simplex virus type 2 infection4.

• Cured by antibiotics: clindamycin or metronidazole, but there is high risk of reoccurrence5.

1 Hill. 1993. Obstet. Gynecol. 169:2,2:450-454. 2 Flynn et al. 1999. J.Fam.Prac. 48:11:885-892. 3 Martin et al. 1999. J. Infect. Dis. 180:6:1863-1868.4 Cherpes et al. 2003 Sex. Transm. Dis. 30:5:405-410.5 Uehara et al. 2006. Int J Antimicrob Agents. 28.1. S30-S34.

9

Problems associated with the treatment of BV

Credit: Stem Jems / Photo Researchers, Inc.

VagiforteVagiforte capsules and tablets contain a mixture of lyophilized lactic acid bacteria, namely Lactobacillus acidophilus, Bifidobacterium bifidum and Bifidobacterium longum, which are natural inhabitants of the human vagina and intestinal tract

www.bioflora.co.za

intestinal tract.

Lactic acid bacteria control the overgrowth of pathogenic microorganisms in the human digestive tract and prevent their transfer to the uro-genital tract. Administration of high doses of these bacteria helps to prevent the development of vaginal thrush caused by Candida albicans, frequently associated with broad-spectum antibiotic treatment.

10

Can we consider the “strain replacement

Alternatives?

therapy” approach as an alternative to use of highly‐concentrated and target‐deliverable specific antimicrobials?

• Migrate to the surface of the epithelial cells

Adh t th ith li l ll

Bottleneck of the strain replacement therapy

In order to succeed in a strain replacement therapy approach, the probiotic has to:

• Adhere onto the epithelial cells

• Successfully colonize the epithelial cells and develop a functional biofilm

• Finally, if it will survive all the previous phases, start producing antimicrobials such as hydrogen peroxide, bacteriocins, lactic acid etc.

Lactobacilli protect the vagina from overgrowth of pathogens by producing:

lactic acids (0 7 2 5 m /ml)

Vaginal lactobacilli

•lactic acids (0.7 – 2.5 mg/ml)

•hydrogen peroxide (82% of natural isolates)

•bateriocins (73% of natural isolates)

63% of natural isolates produce all three defense factors

Aroutcheva et al.. 2001. Am J Obstet Gynecol, 185(2), 375-9

11

Think twice BEFOREyou put it into your mouth

Potential Subtilosin Applications

• Subtilosin has strong antimicrobial activity against

Gardnerella vaginalis, the organism responsible for

bacterial vaginosis (BV)bacterial vaginosis (BV)

– BV is typically treated with conventional antibiotics

• Up to 30% of cases return with developed antibiotic resistance

– Antibiotic‐resistant BV infections can dramatically increase the

likelihood of contracting HIV and progression of the virus

12

WHAT? WHY?‐ Helps to restore and maintain ‐ All substances combinedhealthy status

‐ Eliminates abnormal discharge ‐ Subtilosin

‐ Eliminates odor ‐ Subtilosin

‐ Prevents itching and burning ‐ Subtilosin, saponin,sensation poly‐lysine, pentocin

‐ Contraceptive ‐ Lactic acid, subtilosin

‐ Antiviral ‐ Zn lactate

late

cris

p_la

rge.

jp

www.nonchalantmom.blogspot.com

http

://w

ww

.bar

sare

food

.com

/wp-

cont

ent/u

ploa

ds/2

009/

03/c

hoco

www.cookerati.com

13

Lactospore®: a Probiotic of Choice

L. sporogenes was first isolated and described in 1933 by L.M. Horowitz‐Wlassowa and N.W. Nowotelnow.

It was later classified as B. coagulans since this strain possesses key features that are identical to the aforementioned spore‐former.

It should be mentioned that in many cases, commercial products containing B. coagulans use the name L. sporogenes on the labels for marketing purposes, although it is not an accepted name for this species according to the Bergey’s Manual of Determinative Bacteriology.

Clinical trials with L. sporogenes have proven successful in the treatment of gastrointestinal disorders, non‐specific vaginitis, aphthous stomatitis, hepatic encephalopathy and in growth improvement of farm animals.

Supernatant of L. sporogenesinhibits S. mutans

Lactospore®: a Probiotic of Choice

B. coagulans culture produces only the beneficial L‐(+) form of lactic acid in the gastrointestinal tract. Because of its convenient storage, manufacturing and handling attributes, the strain does not require refrigeration to maintain its reported health benefitsreported health benefits.

Lactospore®’s GRAS status was determined by an independent panel of scientists, assembled by Soni & Associates, who reviewed safety and toxicology data. GRAS approval will now allow food manufacturers to add Lactospore® to a variety of foods and beverages ranging from baked goods to milk products, soups, snacks, candy, non‐alcoholic beverages and even instant tea and coffee.

14

Trade Name Composition Dosage form Therapeutic useSPORLACLACTOSPORE

L. sporogenes*B. coagulans tablet powder

Lactose intolerance, gastro-intestinal infections, hyperchole- sterolemia, hepatic coma and precoma.

SANVITA L. sporogenes *, Vitamins B, L-lysine monochloride granules

Adjuvant to antibiotic therapy, convalescence therapy, enhancing immune response

SANVITONEL. sporogenes*, vitamins B, minerals antioxidants fungal diastase.

capsulesGeriatric and convalescence therapy, enhancing immune response, improves digestion.

MYCONIPÒ L. sporogenes* vaginal tablets Non-specific vaginitis, leucorrhea and after antifungal /antiprotozoal treatment.

BACTOLYTE L sporogenes* isotonic salts powder oral rehydration therapy

Some commercially available preparations of B. coagulans

BACTOLYTE L. sporogenes isotonic salts powder oral rehydration therapy

AMPILAC L. sporogenes*, ampicillin capsulesAntibiotic with adjuvant for nutritional status enhancement and maintenance of gastrointestinal ecological balance

LACBON L. sporogenes* tablets powderDiarrhea, dyspepsia, uticaria, eczema, strophilus, flora modifier after chemotherapy.

BECOPLUS L. sporogenes*, B complex, zinc capsule powder B complex deficiency adjuvant with

antibiotics

NUTROLIN-B L. sporogenes*, B complex capsule powder B complex deficiency adjuvant with antibiotics

GUTFLOR L. sporogenes*, B complex tablet adjuvant with antibiotics

VIZYLAC L. sporogenes*, B complex capsule tablet adjuvant with antibiotics and chemotherapeutic agents

http://www.lactospore.com/

In its February 14, 2008 edition, the British medical journal The Lancet published the findings of the study into the effect of probiotics on acute pancreatitis.

“Utrecht clinical trial”

p

The most important conclusion is that in people with severe acute pancreatitis, probiotics did not reduce the number of infections but resulted in a higher number of deaths.

http://www.umcutrecht.nl

Gene(s) Resistance phenotype Mechanism of action Location (when studied) References

Lactobacillus

erm(B)/erm(C)/erm(T) erm(LF)/erm(GT) MLS Ribosomal methylation Plasmid transposon

chromosome

Ammor et al. (2008a), Aquilanti et al. (2007), Cauwerts et al. (2006), Gfeller et al. (2003), Hummel et al. (2007), Klare et al. (2007), and Tannock et al. (1994)

mef(A) Macrolide Efflux – Cauwerts et al. (2006) Ahn et al (1992)

Examples of the main antibiotic resistance determinants identified and characterized in lactobacilli and bifidobacteria

Cat Chloramphenicol Antibiotic acetylation PlasmidAhn et al. (1992), Hummel et al. (2007), and Lin et al. (1996)

tet(W)/tet(M)/tet(S) tet(O)/tet(Q)/tet(36) tet(Z)/tet(W/O) tet(O/W/32/O/W/O)

Tetracycline Ribosomal protection Plasmid transposon chromosome

Ammor et al. (2008a), Ammor et al. (2008b), Aquilanti et al. (2007), Klare et al. (2007), and van Hoek et al. (2008b)

tet(K)/tet (L) Tetracycline Efflux Plasmid Ammor et al. (2008b), Aquilanti et al. (2007)

Bifidobacterium

tet(W)/tet(M)/tet(O) tet(W/32/O)/tet(O/W) Tetracycline Ribosomal protection Chromosome

Ammor et al. (2008a), Florez et al. (2006), Kazimierczak et al. (2006), van Hoek et al. (2008b)

tet(L) Tetracycline Efflux Chromosome van Hoek et al. (2008b) erm(X) MLS Ribosomal methylation Transposon van Hoek et al. (2008a)

http://www.springerlink.com/content/v48881431j1521j8/fulltext.html

15

Study Age Risk factors Probiotic Method of identification Form of sepsis

Rautio et al. (1999) 74 Diabetes mellitus LGG API 50 CH; PFGE of DNA restriction fragments Liver abscess

Mackay et al. (1999) 67Mitral regurgitation L. rhamnosus 3 × 109

cfu/day API 50 CH; Pyrolysis mass spectrometry Endocarditis

Dental extraction

Kunz et al. (2004)

3 monthsPrematurity

LGG No confirmatory typing BacteremiaShort gut syndrome

10 weeksPrematurity; Inflamed intestine; LGG PFGE of DNA restriction

fragments BacteremiaShort gut syndrome;

De Groote et al. (2005) 11 months

Prematurity; Gastrostomy;

LGG ¼ capsule/day rRNA sequencing BacteremiaShort gut syndrome; CVC;

Cases of bacterial sepsis in humans temporally related to probiotic use

Parenteral nutrition; Rotavirus diarrhea

Land et al. (2005) 4 months

Cardiac surgery; Antibiotic diarrhea LGG 1010 cfu/day

Repetitive element sequence-based PCR DNA fingerprinting

Endocarditis

Cerebral palsy; Jejunostomy feeding; CVC; Antibiotic diarrhea

LGG 1010 cfu/day Repetitive element sequence-based PCR DNA fingerprinting

Bacteremia

Richard et al. (1988)

47 Not stated B. subtilis 8 × 109

spores/day Antibiotic susceptibility Bacteremia



63 Neoplastic disease B. subtilis 8 × 109




Oggioni et al. (1998) and Spinosa et al. (2000) 73 Chronic lymphocytic

leukemiaB. subtilis 109 spores /day 16S rRNA sequencing Bacteremia


Assessment NotesPresence of antibiotic resistance genes Commonly used safety assessment

Mobility of antibiotic resistance genes Commonly used assessment; particularly relevant for Enterococcus

Adhesion to host tissues Not recommended as part of safety assessment (Vankerckhoven et al., 2008b)

Proposed in vitro safety assessments of probiotics

Resistance to host defense mechanisms Commonly used safety assessment(Vesterlund et al., 2007)

Presence of virulence genes and toxic metabolites

Particularly relevant for Bacillus and Enterococcus (Tompkins et al., 2008)

Hemolysis Very rare among probiotics (Vesterlund et al., 2007)

Bile salt deconjugation Irrelevant as safety measurement (Vankerckhoven et al., 2008b)

Presence of macrocapsules Rarely used safety assessment (Baumgartner et al., 1998)


If the science of probiotics holds up in clinical trials,...

...yogurt could replace many pharmaceutical drugs.

http://www.usprobiotics.org/news/healing_power.htm

pro biotics

Documents