1. Probiotics Terms:
Probiotic – Probiotics are live microorganisms (bacteria or yeasts) which, when administered in adequate amounts, confer a health benefit on the host
Prebiotic - nutritional supplement taken to increase the amounts of beneficial bacterial in the gut or vagina. Example “FOS” (fructose oligosaccharides)
Biotherapeutic agent - microorganism used for specific therapeutic activity in humans
Nutriceutical - food products with beneficial effects in preventing or treating diseases

2. Predominant Flora: Stomach
Stomach (0-103 cfu/ml): Gram+ aerobes, Lactobacillus & Streptococcus

3. Predominant Flora: Vagina
Vagina: diverse aerobes & anaerobes including Lactobacillus jensenii, Lactobacillus acidophilus, Lactobacillus casei.

4. Predominant Flora: Urinary Tract
Kidneys: sterile
Bladder: sterile
Urethra: E. coli

5. Predominant Flora: Intestines
Small intestine: Proximal ileum ( cfu/ml) aerobic Gram+ Distal ileum ( cfu/ml) Gram- anaerobes
Colon ( cfu/ml): Bacteroides, Eubacteria, Peptostreptococci, E. coli, Bifidobacterium, Fusobacteria

6. Functions of Normal Flora
Digestion
Production of vitamins
Mucosal maturation
Stimulate Immune System
Attachment
Intestinal transit
Colonization resistance

7. Use of Probiotics in Larger Controlled Trials in Humans
Prevention of Diarrhea
antibiotic associated diarrhea
infantile diarrhea
traveler’s diarrhea
Treatment of Diarrhea
Clostridium difficile disease
acute diarrhea - pediatric and adult

8. Saccharomyces boulardii and Antibiotic Associated Diarrhea in Hospitalized Patients N=180; site: University of Washington, Harborview Hospital
Start Antibiotic
Stop Antibiotic
Stop Study
Yeast continued for 14d
Start Yeast (within 48h)

9. Surawicz et al., Gastroenterol. 1989;96:981

10. Saccharomyces boulardii and Beta lactam Antibiotic Associated Diarrhea in Hospitalized Patients N=193; site: University of Washington, University of Kentucky
Start Antibiotic
Stop Antibiotic
Stop Study
yeast or placebo continued for 3d
Start yeast or placebo

11. McFarland et al. Am J Gastroenterol 1995;90:439-448

12. Lactobacillus GG & Prevention of Infantile Nosocomial Diarrhea [Methods]
DBPC in Poland
81 hospitalized children (1-36 months old)
No diarrhea on admission
Randomized during stay: – LGG (12 x 109 CFU/d) – Placebo
Szajewska H. J Pediatr 2001;138:361-5.

13. Lactobacillus GG & Prevention of Infantile Nosocomial Diarrhea [Results]
33.3
*p<0.05
16.7
6.7*
2.2*
Placebo (n=36)
L. GG (n=45)
Szajewska H. J Pediatr 2001;138:361-5.

14. D’Souza et al., BMJ 2002;324:1361

15. Lactobacilli and Pediatric Diarrhea Treatment (L. rhamnosus and L
Lactobacilli and Pediatric Diarrhea Treatment (L. rhamnosus and L. reuteri in hospital setting)
N=69 Rosenfeldt et al., Pediatr Infec Dis 2002;21:411

16. Huang, et al. , Digestive Diseases and Sciences, Vol. 47, No
Huang, et al., Digestive Diseases and Sciences, Vol.47, No. 11 (Nov 2002)

20. McFarland et al., JAMA; 271, 1913-1918, (1994).

21. S. boulardii & High Dose Vancomycin for C. difficile Disease
50%
*p=0.05
16.7%*
Placebo (n=14)
S. boulardii (n=18)
Surawicz CM. Clin Infect Dis 2000;31:

22. Rates of Clostridium difficile per Patients in the United Kingdom General Practice Research Database
Dial, S. et al. JAMA 2005;294:
Copyright restrictions may apply.

23. Comparison of Community-Acquired Matched Cases and Controls--Medication Variables
Dial, S. et al. JAMA 2005;294:
Copyright restrictions may apply.

24. Clostridium difficile Disease
C. difficle makes 2 toxins. Recent strains are more toxinogenic
severity ranges from simple antibiotic associated diarrhea to mild colitis to pseudomembranous colitis to toxic megacolon to death
Relapses following treatment are common
Risk factors are antimicrobial exposure; recently gastric acid suppressive therapy has also been found to be a significant risk
All antibiotics have some (undefined) risk but those impacting the anaerobic intestinal microflora may have a higher risk (beta lactams, clindamycin, tetracyclines, etc)
Treatment is metronidazole 250mg QID as a first try. If treatment failure or relapse, use vancomycin PO 125mg QID. If failure, 500mg QID.
Use Saccharomyces boulardii probiotic to prevent relapses. Dose is 500mg BID for 4-6weeks.

25. Other Uses for Probiotics –Limited Data
Crohn’s Disease
Ulcerative Colitis
Pouchitis
Allergy/Exema
Irritable Bowel Syndrome Dental caries
High Cholesterol Urinary Tract Infections
Helicobacter pylori
Lactose Intolerance
Candida vaginal infections
Bacterial Vaginosis

26. Potential Advantages and Disadvantages of Probiotics
Multiple Mechanisms of Action
Resistance is Infrequent
Use May Reduce Exposure to Antibiotics
Delivery of Microbial Enzymes
Well Tolerated
Benefit to Risk Ration is Favorable
Few Controlled Trials
Persistence Possible
Translocation Possible
Transfer of Resistance Plasmids?
Infection Possible
Quality Control Issues
Regulatory Issues in USA

29. Lactobacillus rhamnosus GG Dietary Supplement: Culturelle

30. Saccharomyces boulardii Dietary Supplement: Florastor

32. Evidence supporting commercially available (USA) probiotics*
condition L. acidophilus L. reueri LGG Sb
AAD
Uneven
Good
Acute Adult ?
Acute pediatric
Traveler diarrhea
Fair
C. dif
Limited BV
Good**
Good***
L. acidophilus=Lactinex; L. reueri=Probiotica; LGG=Culturelle; Sb=Florastor; ** strains tested not yet available in USA

33. Probiotics Summary
Living microorganisms with multiple mechanisms of action
Good safety profile
Some applications to prevent and treat infectious diseases
An alternative to antibiotics in some situations
May have other applications, e.g. allergy, cancer, colitis, IBS
Product selection is very important