M I C H A E L C H I K I N D A S

To hell with yogurt.

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

TheBulgarianfarmer's longevityandhealthylife aretheresultofthe consumptionoffermented dairyproducts. E.Metchnikoff

Probiotics definitions
Published Definition Substances produced by microorganisms which promote the growth of other microorganisms Organisms and substances which contribute to intestinal microbial balance A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance 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 Living microorganisms, which upon ingestion in certain numbers, exert health benefits beyond inherent basic nutrition Reference Lilly and Stillwell 1965 Parker 1974 Fuller 1989 Havenaar and Huis Int Veld 1992 Schaafsma 1996 Naidu et al. 1999

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

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

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

Schrezenmeir and de Vrese 2001 FAO/WHO report, October 2001

ProbioticMarket
Globalmarketiscurrentlyvaluedat$22.6billionand projectedtoreach$28.8billionin2015 TargetconsumersaremainlylocatedinJapan,Europeand USA Between2003and2005,USprobioticmarketgrewby8.7%to $5bn 5%growthuntil2013 Growthfactorsinclude: Consumerunderstandingoftheeffectofnutritionon health Risinghealthcarecosts
Source: Tallon 2009; Global Probiotic Market to Grow Analyst. FLEXNEWS. 27 Sept 2010. Web. 27 Sept 2010.

USProbioticProducts
Dairydominatethemarket Beveragesandsnacksgrowinsize
ProbioticproductslaunchedinUnitedStates,bycategory(20002010)
18 16

Num of Products ber s

14 12 10 8 6 4 2 0 2000 2003 2004 2005 2006 2007 2008 2009 2010

Year
Dairy Non-Alcoholic Beverages Snacks Other

Source: Mintel GNPD 22 Jan 2011

Humanprobiotics
Humanprobioticscanbegroupedaccordingtothe ecologicalnichesofthehumanbodytheyoccupy(or thepartofthebodytheydelivertheirhealth promotingactionto),suchas: Gastrointestinalprobiotics G i i l bi i Skinprobiotics Scalpprobiotics Probioticsoftheoralcavity Probioticsoftheunderarmandfeet Urogenital(includingvaginal)probiotics

ProbioticsSpecies
Lactobacillus species Lb. acidophilus Lb. amylovorus Lb. brevis Lb. casei Lb. casei ssp. rhamnosus Lb. crispatus Lb. delbrueckii ssp. bulgaricus Lb. fermentum Lb. gasseri Lb. helveticus Lb. johnsonii Lb. lactis Lb. paracasei Lb. plantarum Lb. reuteri Bifidobacterium species Bf. adolescentis Bf. animalis Bf. bifidum Bf. breve Bf. infantis Bf. Bf lactis Bf. longum Other species Bacillus cereus Clostridium botyricum Enterococcus faecalis Enterococcus faecium Escherichia coli Lactococcus lactis ssp ssp. cremoris Lactococcus lactis ssp. lactis Leuconostoc mesenteroides ssp. dextranicum Pediococcus acidilactici Propionibacterium freudenreichii Saccharomyces boulardii Streptococcus salivarius ssp. thermophilus

Cited by W.H. Holzapfel and U. Schillinger, Introduction to pre- and probiotics, Food Research International 35 (2002), pp. 10916

Examplesofprobioticstrainsusedinpreventionandtreatmentofsomediseases

Disorders Diarrhea caused by pathogenic bacteria and viruses

Strains

Clinical outcomes

Lb. rhamnosus GG, Lb. casei Bf. lactis BB-12, Bf. Prevention and treatment of acute diarrhea bifidum Sc. thermophilus caused by rotaviruses in children Lb. johnsonii La1, Lb. salivarius, Lb. acidophilus LB Lb. rhamnosus GG Lb. rhamnosus GG, Lb. rhamnosus LC-705, Lb. casei Shirota, Lb. acidophilus LA-2, Bifidobacterium sp., Propionibacterium sp. Lb. Lb casei Shi t Lb rhamnosus HN001 Lb i Shirota, Lb. h HN001, Lb. acidophilus HN017, Bf. Lactis HN019 Lb. rhamnosus GG, Bf. lactis BB-12 Inhibition of the pathogen growth and decrease urease enzyme activity necessary for the pathogen to remain in the acidic environment of the stomach Remediation in inflammatory conditions through modulation of the gastrointestinal microflora Prevention or delay of the onset of certain cancers Enhancement of immune parameters Prevention of allergic diseases onset

Helicobacter pylori infection and complications

Inflammatory diseases and bowel syndromes Cancer in gastrointestinal tract

Mucosal immunity Allergic symptoms

Cardiovascular disease

Lactobacillus sp.

Prevention and therapy of ischemic heart syndromes

Bacterial and yeast vaginitis Urinary tract infections

Lb. acidophilus, Lb. rhamnosus GG Lactobacillus GR-1, Lactobacillus B-54, Lactobacillus RC-14

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

Probioticlacticacidbacteriamarketedworldwide
Strains Lactobacillus casei Shirota Lactobacillus crispatus CTV05 Lactobacillus reuteri MM53 Lactobacillus casei F19 Bifidobacterium lactis HN019 Lactobacillus rhamnosus GG Propionibacterium freudenreichii ssp. shermanii JS Lactobacillus acidophilus NCFM Lactobacillus acidophilus NCFB 1748 Lactobacillus johnsonii LA1 (NCC 533) Lactobacillus acidophilus LA10 (NCC 90) Lactobacillus fermentum RC-14 Lactobacillus rhamnosus GR-1 Lactobacillus casei DN-114 001 Bifidobacterium animalis DN-173 010 Lactobacillus plantarum 299v Lactobacillus rhamnosus 271 Lactobacillus casei CRL 431 Bifidobacterium lactis BB-12 Lactobacillus acidophilus LA-5 Lactobacillus bulgaricus LBY27 Streptococcus thermophilus STY-31 Rhodia, USA Nestl, Nestl Switzerland Urex, Canada Danone, France Probi AB, Sweden Chr. Hansen, USA Origin Yakult, Japan Gynelogix, USA BioGaia, Sweden Arla Foods, Denmark/Sweden Danisco, France Valio, Finland

Adapted from FAO/WHO 2001

Human probiotics Human probiotics can be grouped according to Gastrointestinalprobiotics

the ecological niches of the human body they occupy (or the part of the body they deliver their health-promoting action to), such as: Gastrointestinalprobiotics G i i l bi i Skinprobiotics Scalpprobiotics Probioticsoftheoralcavity Probioticsoftheunderarmandfeet Urogenital(includingvaginal)probiotics

ProbioticProducts
Dairyfoods

Beverages,yogurt,kefir,icecream,cheese
Nondairyfoods

Beverages,bars,chocolate,cereal,pizza, g p condiments
Dietarysupplements

Infantformula,drops,tablets,capsules,powders
Clinicaltherapeuticsandhealthsupporting/promoting formulations

NonDairyBeverages
Product Company Type Strain Lactobacillus plantarum 299v, Bifidobacterium lactis Bi-07 (Probi) Dose 20 bn per 300ml* Claim Clinically proven to promote healthy digestion and support natural immunity Helps the bodys p y natural defenses Helps body to increase iron uptake by about 50% Enhances natural defenses Help promote healthy digestive and immune system GoodBelly NextFoods Juice Drink

Bravo Friscus

Skanemejerier

% 100% Juice

Lactobacillus plantarum HEAL9, Lactobacillus paracasei 8700:2 (Probi)

4bn per p 1L

ProViva Female

Danone

Juice Drink

Lactobacillus plantarum 299v (Probi)

Not provided

Gefilus

Valio

Juice

Lactobacillus rhamnosus GG (Valio)

50 bn per 1L

Naked Probiotic

PepsiCo

Juice

Bifidobacterium lactis HN019

5 bn per 300ml

Swedesfirstwithnondairyprobiotic"littlebottle
www.new-nutrition.com/newspage/030403a.htm

Skanes 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 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 Sknemejeriers 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

http://goodbelly.com/

Thefirstprobioticjuicewaslaunchedinthefallof2007byNextFoods, foundedbySteveDemos(whoalsofoundedSilksoymilk).GoodBelly isan organicfruit juicebasedprobioticbeveragethatcontainsapatented probioticcalledLactobacillusplantarum 299v,whichwasdevelopedinthe U.K.andhastestedwellforitseffectsonIrritableBowelSyndrome. Twentybillionlivebacteriaareineachservingjuicestoprovidedigestive health.Threeflavorsinclude:BrilliantBlueberry,PeachMangoand StrawberryRosehip. CLAIM: GoodBelly isspecificallydesignedtobeenjoyeddailyinorderto boostyourimmunesystemandimprovedigestivehealthbyreplenishing yourbodyshealthymicroflora.GoodBellys patentedLp299v probiotic strainhasbeen clinicallyproven inover15yearsofresearch.

Tokyo(JCN) JapanesefoodconglomerateKagome announcedtheirlaunchofalacticacidbacteria beverageseries,Labre,onMarch14,2006 Thenewproduct,whichcontains Lactobacillusbrevissubsp.coagulans (Labre), helpsmaintainhealth.Itcomesinthree sizes:130ml,100mland80ml.Pricesare105 yen(90cents)fora130mlbottleand170yen ($1.45)forthree80mlpacks.The100ml ($1 45) for three 80ml packs The 100ml bottle,whichwillbeavailableviahome deliveryonly,willbeopenpriced.

Kagomeaimedtogenerate10billionyen($86mil) fromsalesofthenewbeverageinthefirstyear.

Activiaisagreattastinglowfat yogurtfromDannonthat containsBifidusRegularisa naturalprobioticculturethat canhelpregulateyourdigestive systembyhelpingreducelong intestinaltransittime.

Do I really want it to go faster?!

September23,2009 DannonsettlesclassactionsuitoverActiviahealthclaims Dannonhasreachedasettlement inaclassactionlawsuitfiled overmisleadingadvertisingonitsActiviaandDanActivelinesof yogurt,accordingtotheAssociatedPress. Thehealthclaimsindicatedthattheyogurt'sbacteriawouldhelp withdigestionorwiththeimmunesystem. Aspartofthesettlement,theWhitePlains,N.Y.companydoes As part of the settlement the White Plains N Y company does notadmitanywrongdoing butwillcreatea$35millionfundto reimbursequalifiedconsumersupto$100forproducts purchased. http://www.csgrr.com/Dannon/

http://bx.businessweek.com

Humanprobiotics
Humanprobioticscanbegroupedaccordingtothe ecologicalnichesofthehumanbodytheyoccupy(or thepartofthebodytheydelivertheirhealth promotingactionto),suchas:

Probioticsoftheoralcavity
Gastrointestinalprobiotics G i i l bi i Skinprobiotics Scalpprobiotics Probioticsoftheoralcavity Probioticsoftheunderarmandfeet Urogenital(includingvaginal)probiotics

K12story
Whenhewasjustaboyof12,JohnTaggcontracted anespeciallybadcaseofstrepthroatthatledto rheumaticfever. Rheumaticfeverisadelayed, autoimmunereactiontothebacteriathatcauses strepthroat Streptococcuspyogenes.Itisavery painful,inflammatoryconditionthatmakesjoints swellandredden. Becauserheumaticfevercan permanentlyweakenanddamagetheheart,itis importanttopreventarecurrenceofstrep.John sdoctorputhimonacourseof important to prevent a recurrence of strep Johns doctor put him on a course of antibioticseverydayfor10years,acommonprocedureatthetime. ThischildhoodexperienceinspiredProfessorTaggtodevotehislifetothestudyof friendlyprobioticbacteriathatcanpreventstrepthroatandotherinfectionsthatenter throughyourmouth. Today,morethan35yearslater,ProfessorTaggisaworldrenownedmicrobiologistfrom theUniversityofOtagoinNewZealandwhosetargetedresearchhasledtothe discoveryofS.salivarius BLISK12,arevolutionaryORALprobioticthatprevents infection(includingstrepthroat)whereitbegins inyourmouth.
http://culturedcare.com/

K12story
BLISK12isanew,advancedprobioticdiscovered byProfessorJohnTaggfromtheDepartmentof MicrobiologyandImmunologyattheUniversityof OtagoinNewZealand. BLISstandsforBacteriocinLikeInhibitory Substanceandisthenaturallyoccurring componentofcertainstrainsofmicroorganisms component of certain strains of microorganisms (probiotics)whichcontrolundesirableand diseasecausingbacteria.BLISK12isthespecial BLISprobioticstrainderivedfromthefriendly bacteriaS.salivarius. Ithasbeenshowntosafelycontrolthebacteria thatfrequentlycausesstrepthroat,earache, upperrespiratoryinfections,sinusinfectionsand halitosis(badbreath).
http://www.springerlink.com/content/dg56pk5k48l6w5h1/fulltext.html http://culturedcare.com/

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
Humanprobioticscanbegroupedaccordingtothe ecologicalnichesofthehumanbodytheyoccupy(or thepartofthebodytheydelivertheirhealth promotingactionto),suchas: Gastrointestinalprobiotics G i i l bi i Skinprobiotics Urogenital probiotics Scalpprobiotics Probioticsoftheoralcavity Probioticsoftheunderarmandfeet Urogenital(includingvaginal)probiotics

Bacterialvaginosis
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. et al. 1999. J.Fam.Prac. 48:11:885-892.

2 Flynn 3

Martin et al. 1999. J. Infect. Dis. 180:6:1863-1868. et al. 2003 Sex. Transm. Dis. 30:5:405-410.

4 Cherpes 5 Uehara

et al. 2006. Int J Antimicrob Agents. 28.1. S30-S34.

Problemsassociatedwith thetreatmentofBV

Credit: Stem Jems / Photo Researchers, Inc.

Vagiforte
Vagiforte 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 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.

www.bioflora.co.za

Alternatives?
Canweconsiderthestrainreplacement therapyapproachasanalternativetouse ofhighlyconcentratedandtarget deliverablespecificantimicrobials?

Bottleneckofthestrain replacementtherapy
Inordertosucceedinastrainreplacementtherapy approach,theprobiotichasto: Migratetothesurfaceoftheepithelialcells Adh Adhereontotheepithelialcells t th ith li l ll Successfullycolonizetheepithelialcellsand developafunctionalbiofilm Finally,ifitwillsurviveallthepreviousphases, startproducingantimicrobialssuchashydrogen peroxide,bacteriocins,lacticacidetc.

Vaginallactobacilli
Lactobacilliprotectthevagina fromovergrowthofpathogens byproducing: lacticacids(0.7 2 5 m /ml) lactic acids (0 7 2.5mg/ml) hydrogenperoxide(82%ofnaturalisolates) bateriocins(73%ofnaturalisolates) 63%ofnaturalisolatesproduceallthreedefensefactors
Aroutcheva et al.. 2001. Am J Obstet Gynecol, 185(2), 375-9

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ThinktwiceBEFORE youputitintoyourmouth

PotentialSubtilosinApplications
Subtilosinhasstrongantimicrobialactivityagainst Gardnerellavaginalis,theorganismresponsiblefor bacterialvaginosis(BV) bacterial vaginosis (BV)
BVistypicallytreatedwithconventionalantibiotics
Upto30%ofcasesreturnwithdevelopedantibioticresistance

AntibioticresistantBVinfectionscandramaticallyincreasethe likelihoodofcontractingHIVandprogressionofthevirus

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WHAT? Helpstorestoreandmaintain healthystatus Eliminatesabnormaldischarge Eliminatesodor Preventsitchingandburning sensation Contraceptive Antiviral

WHY? Allsubstancescombined

Subtilosin Subtilosin Subtilosin,saponin, polylysine,pentocin Lacticacid,subtilosin Znlactate

www.nonchalantmom.blogspot.com

www.cookerati.com

http://www.barsarefood.com/wp-content/uploads/2009/03/chocolatecrisp_large.jp

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Lactospore:aProbioticofChoice
L.sporogeneswasfirstisolatedanddescribedin1933byL.M.Horowitz WlassowaandN.W.Nowotelnow. ItwaslaterclassifiedasB.coagulans sincethisstrainpossesseskeyfeatures thatareidenticaltotheaforementionedsporeformer. Itshouldbementionedthatinmanycases,commercialproductscontaining B.coagulans usethenameL.sporogenes onthelabelsformarketing purposes,althoughitisnotanacceptednameforthisspeciesaccordingto theBergeysManualofDeterminativeBacteriology.

Clinicaltrialswith L.sporogenes haveproven successfulinthetreatmentof gastrointestinaldisorders,non specificvaginitis,aphthous stomatitis,hepatic encephalopathyandingrowth improvementoffarmanimals.

Supernatant of L. sporogenes inhibits S. mutans

Lactospore:aProbioticofChoice
B.coagulanscultureproducesonlythebeneficialL(+)formoflacticacidinthe gastrointestinaltract.Becauseofitsconvenientstorage,manufacturingand handlingattributes,thestraindoesnotrequirerefrigerationtomaintainits reportedhealthbenefits. reported health benefits LactosporesGRASstatuswasdeterminedbyanindependentpanelof scientists,assembledbySoni&Associates,whoreviewedsafetyand toxicologydata.GRASapprovalwillnowallowfoodmanufacturerstoadd Lactospore toavarietyoffoodsandbeveragesrangingfrombakedgoodsto milkproducts,soups,snacks,candy,nonalcoholicbeveragesandeveninstant teaandcoffee.

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SomecommerciallyavailablepreparationsofB.coagulans
Trade Name
SPORLAC LACTOSPORE SANVITA

Composition
L. sporogenes* B. coagulans

Dosage form
tablet powder

Therapeutic use
Lactose intolerance, gastro-intestinal infections, hyperchole- sterolemia, hepatic coma and precoma. Adjuvant to antibiotic therapy, convalescence therapy, enhancing immune response Geriatric and convalescence therapy, enhancing immune response, improves digestion. Non-specific vaginitis, leucorrhea and after antifungal /antiprotozoal treatment. oral rehydration therapy Antibiotic with adjuvant for nutritional status enhancement and maintenance of gastrointestinal ecological balance Diarrhea, dyspepsia, uticaria, eczema, strophilus, flora modifier after chemotherapy. B complex deficiency adjuvant with antibiotics B complex deficiency adjuvant with antibiotics adjuvant with antibiotics adjuvant with antibiotics and chemotherapeutic agents

L. sporogenes *, Vitamins B, granules L-lysine monochloride L. sporogenes*, vitamins B, minerals antioxidants fungal capsules diastase. L. sporogenes* vaginal tablets

SANVITONE MYCONIP BACTOLYTE AMPILAC

L. sporogenes L sporogenes* isotonic salts powder L. sporogenes*, ampicillin capsules

LACBON BECOPLUS NUTROLIN-B GUTFLOR VIZYLAC

L. sporogenes* L. sporogenes*, B complex, zinc L. sporogenes*, B complex L. sporogenes*, B complex L. sporogenes*, B complex

tablets powder capsule powder capsule powder tablet capsule tablet

http://www.lactospore.com/

Utrechtclinicaltrial
InitsFebruary14,2008edition,theBritish medicaljournalTheLancetpublishedthe findingsofthestudyintotheeffectofprobiotics onacutepancreatitis. p Themostimportantconclusionisthatinpeople withsevereacutepancreatitis,probioticsdidnot reducethenumberofinfectionsbutresultedina highernumberofdeaths.
http://www.umcutrecht.nl

Examplesofthemainantibioticresistancedeterminants identifiedandcharacterizedinlactobacilliandbifidobacteria
Gene(s) Lactobacillus 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) Cauwerts et al. (2006) Ahn et al (1992) al. (1992), Hummel et al. (2007), and Lin et al. (1996) Ammor et al. (2008a), Ammor et al. (2008b), Aquilanti et al. (2007), Klare et al. (2007), and van Hoek et al. (2008b) Ammor et al. (2008b), Aquilanti et al. (2007) Ammor et al. (2008a), Florez et al. (2006), Kazimierczak et al. (2006), van Hoek et al. (2008b) van Hoek et al. (2008b) van Hoek et al. (2008a) Resistance phenotype Mechanism of action Location (when studied) References

erm(B)/erm(C)/erm(T) erm(LF)/erm(GT)

MLS

Ribosomal methylation

Plasmid transposon chromosome

mef(A) Cat tet(W)/tet(M)/tet(S) tet(O)/tet(Q)/tet(36) tet(Z)/tet(W/O) tet(O/W/32/O/W/O) tet(K)/tet (L) Bifidobacterium tet(W)/tet(M)/tet(O) tet(W/32/O)/tet(O/W) tet(L) erm(X)

Macrolide Chloramphenicol

Efflux Antibiotic acetylation

Plasmid

Tetracycline

Ribosomal protection

Plasmid transposon chromosome

Tetracycline

Efflux

Plasmid

Tetracycline

Ribosomal protection

Chromosome

Tetracycline MLS

Efflux Ribosomal methylation

Chromosome Transposon

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

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Casesofbacterialsepsisinhumanstemporallyrelatedtoprobioticuse
Study Rautio et al. (1999) Mackay et al. (1999) Age 74 67 3 months Kunz et al. (2004) 10 weeks Risk factors Diabetes mellitus Mitral regurgitation Dental extraction Prematurity Short gut syndrome Prematurity; Inflamed intestine; Short gut syndrome; Prematurity; Gastrostomy; Short gut syndrome; CVC; Parenteral nutrition; Rotavirus diarrhea Cardiac surgery; Antibiotic diarrhea Land et al. (2005) 4 months LGG Probiotic Method of identification Form of sepsis API 50 CH; PFGE of DNA Liver abscess restriction fragments L. rhamnosus 3 109 API 50 CH; Pyrolysis mass cfu/day Endocarditis spectrometry LGG LGG No confirmatory typing PFGE of DNA restriction fragments Bacteremia Bacteremia

De Groote et al. (2005)

11 months

LGG capsule/day

rRNA sequencing

Bacteremia

LGG 1010 cfu/day

47 25 Richard et al. (1988) 63 79 Oggioni et al. (1998) and 73 Spinosa et al. (2000)

Cerebral palsy; Jejunostomy feeding; LGG 1010 cfu/day CVC; Antibiotic diarrhea B. subtilis 8 109 Not stated spores/day B. subtilis 8 109 Not stated spores/day B. subtilis 8 109 Neoplastic disease spores/day B. subtilis 8 109 Not stated spores/day Chronic lymphocytic B. subtilis 109 spores leukemia /day

Repetitive element sequence-based PCR DNA fingerprinting Repetitive element sequence-based PCR DNA fingerprinting Antibiotic susceptibility Antibiotic susceptibility Antibiotic susceptibility Antibiotic susceptibility 16S rRNA sequencing

Endocarditis

Bacteremia Bacteremia Bacteremia Bacteremia Bacteremia Bacteremia

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

Proposedinvitro safetyassessmentsofprobiotics
Assessment
Presenceofantibioticresistancegenes Mobilityofantibioticresistancegenes Adhesiontohosttissues Resistancetohostdefensemechanisms Presenceofvirulencegenesandtoxic metabolites Hemolysis Bilesaltdeconjugation Presenceofmacrocapsules

Notes
Commonlyusedsafetyassessment Commonlyusedassessment;particularly relevantforEnterococcus Notrecommendedaspartofsafety assessment(Vankerckhoven etal.,2008b) Commonlyusedsafetyassessment (Vesterlund etal.,2007) ParticularlyrelevantforBacillus and Enterococcus (Tompkinsetal.,2008) Veryrareamongprobiotics (Vesterlund etal., 2007) Irrelevantassafetymeasurement (Vankerckhoven etal.,2008b) Rarelyusedsafetyassessment(Baumgartner etal.,1998)
http://www.springerlink.com/content/v48881431j1521j8/fulltext.html

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

...yogurtcouldreplacemany pharmaceuticaldrugs.

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

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