This document discusses probiotics as a treatment option for diarrhea and irritable bowel syndrome (IBS). It provides details on the types and causes of diarrhea, as well as the pathophysiology and treatment of IBS. Several studies are summarized that show the effectiveness of various probiotic strains, including Saccharomyces boulardii and Lactobacillus rhamnosus GG, in reducing the duration and incidence of diarrhea, as well as alleviating symptoms of IBS. The proposed mechanisms of action for probiotics include inhibition of pathogen growth, anti-toxin effects, and modulation of the intestinal environment.

1. Probiotic
:
A
treatm
ent
option
in
diarrhea
and
IBS

2. DIARRHOEA
• Increase in FREQUENCY, LIQUIDITY, VOLUME of stools
• Stool weight more than/equal to 200 gm/day (western diet) or 450
gm/day (indian diet)
• Diarrhea - WHO defines as passage of loose or watery stools; 3 or
more per day.
• Among children in the U.S., diarrhea accounts for more than 1.5 million
outpatient visits, 200,000 hospitalizations, and ~300 deaths per year.

3. PSEUDO-DIARRHOEA
Increased frequency but with NORMAL VOLUME
Seen due to local inflammation of rectum (IBS, proctitis)
• Patient passes small but frequent stools
TYPES OF DIARRHOEA
• ACUTE: less than 2 weeks
• PERSISTENT: 2-4 weeks
• CHRONIC: more than 4 weeks

4. SYMPTOMS AND SIGNS

5.  Bacterial bowel infection
COMPLICATIONS
 Dehydration
 Infections

6. • Leading cause of childhood morbidity & mortality in developing
countries
• Important cause of malnutrition
• 80% of deaths due to diarrhoea occur in the first two years of life.
• Children <3 years of age in developing countries experience around
three episodes of diarrhoea each year.
Morbidity

7. Epidemiologic features of Diarrhea
• 2 billion cases of diarrheal disease every year
– About 5000 deaths in children every day
– Incidence and risk of mortality are highest in this age group
• About 78% occur in the South-East Asian & African regions

8. ETIOLOGY OF ACUTE DIARRHOEA
Viral :
Rota Virus
 Adenovirus
Norwalk Agent
Bacterial :
 V. Cholera
 ETEC, EIEC
 Salmonella
 Shigella
Campylobacter
Fungal :
 Candida

9. Parasitic Infection
 Giardia Lamblia
 Cryptosporidium
 Entamoeba Histolytica
Drugs
 Laxatives
 Sorbitol
 Antacids
 Lactulose
 Theophylline
 Antibiotics
Diet :
Food Poisoning
Food allergy

10. Treatment
• Elimination of the cause
• IV fluids and electrolytes
• Medications

11. Diarrheal Disease
Current Management
Ofloxacin : Not recommended in children
Amoebic infections are to the tune of 5% in children < 5yrs
Limitations of Prescribing antibiotic in Diarrhea / Dysentry
Ofloxacin : Toxicity and risk of cartilage damage
Ofloxacin / Imidazoles : Bitter taste, Palatability, Nausea
5-8 days of lengthy treatment
Recovery time is 4-5 days after treatment
No effect on improvement of stool consistency
Emerging resistance, not recommened in < 8yrs of age
irrational combinations as H1/2 is different quinolones (12hrs)
Metronidazole(8hrs)
LimitationsLimitations

12. 12
A functional gastrointestinal disorder
symptoms :
abdominal pain
bloating or distension and various
symptoms of disordered defecation.
Thompson et alThompson et al,, 19921992
IRRITABLE BOWEL SYNDROME (IBS)

13. Pathophysiology

14. 14

15. Antidiarrheal medication is one of the
approach for treating IBS
• Loperamide – effective when used prophylactically 2-16mg/d
• Cholestyramine
• Bismuth subsalicylate

16. NORMAL BACTERIAL FLORA OF THE
GI TRACT
• Aerobic and anaerobic bacteria,
• yeast and fungi live into the GI tract 400 m2 of surface area.
• more than 2000 species of commensal bacterial organisms within our
bodies
Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725

17. Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725

18. GI flora components
Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725

19. Probiotics
• Microbes found in the food supply that enhance human health.
Criteria:
• bacteria of human origin
• able to adhere to the intestinal mucosa
• have potential to colonize in the GI tract
• can produce antimicrobial substances,
• stable against bile, HCl, and other acids, enzymes, and oxygen, and
determined to be safe and effective.

20. World Gastroenterology Organisation Practice Guideline Probiotics and prebiotics.
www.worldgastroenterology.org/.../guidelines/19_probiotics_prebiotics
Benefits of probiotics….

21. Mechanism of Action
• Suppression of growth or epithelial binding/invasion by pathogenic bacteria
– 1. Decrease luminal pH
– 2. Secrete antimicrobial peptides
– 3. Inhibit bacterial invasion
– 4. Block bacterial adhesion to epithelial cells

22. Purported mechanisms of action of probiotics.
I.P. Kaur et al. / European Journal of Pharmaceutical Sciences 15 (2002) 1 –9

23. Altered Disease States
Probiotics have been thought to improve or ameliorate a plethora of
states, the most commonly reported upon are:
• Various states of diarrhea
• Inflammatory Bowel Disease
• H. Pylori Ulcers
• Urinary Tract Infections
• Vaginal Candida Overgrowth

24. Diarrhea is the condition most
beneficially treated by probiotic
therapy.
This can include diarrhea associated with
• antibiotics,
• travel,
• gastroenteritis,
• lactose intolerance,
• and Inflammatory Bowel Disease.

25. Commercially used probiotic strains.
Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725

26. Probiotics for Prevention and Treatment of Diarrhea Stefano Guandalini, MD
Use of different probiotics in children

27. ROLE OF
SACCHAROMYCES
BOULARDI

28. Saccharomyces boulardii
• Saccharomyces boulardii (S. boulardii)-yeast isolated from
the skin of Lychees
• non-pathogenic
• thermotolerant yeast
• grows optimally at 370
C.
• It is a live yeast that is available as a lyophilized preparation
for adults as a 250 mg capsule.
Prajapati P, Patel M, Krishnamurthy R. Saccharomyces boulardii- a probiotic of choice. CIBTech Journal of Biotechnology. 2013
Vol. 2 (2) April-June, pp.1-6

29. Properties of S boulardii
• resistant to stomach acids and bile acids
• Although the optimal temperature for most strains of Saccharomyces
range from 22-30 c, S. boulardii survives best at 37 c.
• S. boulardii is a safe and effective biotherapeutic agent for the
treatment of gastrointestinal disease.
Prajapati P, Patel M, Krishnamurthy R. Saccharomyces boulardii- a probiotic of choice.
CIBTech Journal of Biotechnology. 2013 Vol. 2 (2) April-June, pp.1-6

30. Pharmacokinetics
S. boulardii, when given orally -
• steady-state concentrations – 3 days
• clearance- 3-5 d after discontinuation
• half life -6 hours,
• fecal steady state concentration (2 × 107
/g) – 3 days
• some types of fiber (psyllium) increase S boulardii levels by 22%, while
other type of fiber (pectin) shows no effect.
McFarland LV. Systematicv review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol 2010
May 14; 16 (18):2202-2222

31. Stability of S boulardii
• Probiotics may be available as lyophilized or heat-dried preparations.
• Lyophilized preparations -
• stable over one year at room temperature, as long as it is protected
from moisture.
Prajapati P, Patel M, Krishnamurthy R. Saccharomyces boulardii- a probiotic of choice. CIBTech Journal of Biotechnology. 2013 Vol. 2 (2) April-June, pp.1-6

32. Mechanism of Action
McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol 2010 May 14; 16
(18):2202-2222

33. Anti-Microbial Action – Direct Anti-Toxin
Effect
• The anti-toxin action-mainly due to small peptides produced by the
yeast.
• Able to inhibit enterotoxin and cytotoxic activities of C. difficile by
degradation of toxin A and B
• Different types of mechanisms of action.
• luminal action
• trophic action
• mucosal-anti-inflammatory signaling effects.
• S. boulardii may interfere with pathogenic toxins,
• preserve cellular physiology,
• interfere with pathogen attachment,
• interact with normal microbiota
Prajapati P, Patel M, Krishnamurthy R. Saccharomyces boulardii- a probiotic of choice. CIBTech Journal of Biotechnology. 2013 Vol. 2
(2) April-June, pp.1-6

34. Inhibition of Growth and Invasion of
Pathogen
• S boulardii directly inhibits the growth of several pathogens (Candida
albicans, E. coli, Shigella, and cell invasion by Salmonella typhimurium.
• This mode of action important for the treatment of (chronic)
inflammation of the digestive tract.
Prajapati P, Patel M, Krishnamurthy R. Saccharomyces boulardii- a probiotic of choice. CIBTech Journal of Biotechnology. 2013 Vol. 2
(2) April-June, pp.1-6

35. Theodoros Kelesidis and Charalabos Pothoulakis Ther Adv Gastroenterol (2012) 5(2) 111–125

36. Continue…

38. Theodoros Kelesidis and Charalabos Pothoulakis gastrointestinal disorders for the prevention and therapy of Saccharomyces boulardii
Efficacy and safety of the probiotic

39. Research evidence for probiotic use in
inflammatory bowel syndrome (IBS)
• .
• Multi-strain probiotics have been found to provide general relief of
IBS symptoms such as abdominal pain, discomfort, and bloating.
• probiotics have a significant effect in altering the intestinal
environment.
Journal of Gastroenterology and Hepatology

40. Probiotic for irritable bowel syndrome
(IBS)
Bacillus coagulans(L.sporogenes)
• This has been found to provide significant improvement of
bloating and abdominal pain in patients who are diagnosed
with IBS.

41. Lactobacillus rhamnosus GG
• Decreases the intensity and frequency of abdominal pain in children
with IBS
. Bifidobacterium bifidum
• In a clinical trial done on this strain, 47% of people with IBS had
reported improved symptoms of IBS.

42. Bifidobacteria benefits on human health.
Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725

43. Research to Support the Claims

44. #1 Effects of Saccharomyces boulardii in
children with acute diarrhoea
• Aim:to evaluate the effect of S. boulardii in children with acute
diarrhoea.
• Methods: randomise study
• No. of childrens: 200
• Dose: a daily dose of 250 mg (S. boulardii group) or placebo (placebo
group) for 5 days

45. • Conclusion: The placebo-controlled study suggested that S. boulardii
significantly reduced the duration of acute diarrhoea and the durationZ. KURUGO¨ L & G. KOTUROG˘ LUEffects of Saccharomyces boulardii in children with acute diarrhoea. Acta Pædiatrica, 2005; 94: 44–47

46. #2 Saccharomyces boulardii in the
prevention of antibiotic-associated
diarrhoea in children
• Aim: To determine whether S. boulardii prevents antibiotic-
associated diarrhoea in children
• Methods:
• No. of children:269
• Age:6 months to 14 years
• with otitis media and/or respiratory tract infections
• Experimental group :Standard antibiotic treatment plus 250 mg of
S. boulardii
• control group :Standard antibiotic treatment plus placebo

47. Conclusion-S.boulardii effectively reduces the risk of antibiotic-
associated diarrhoea in children.
Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-
controlled trial M. KOTOWSKA, P. ALBRECHT & H. SZAJEWSKA. Aliment Pharmacol Ther 2005; 21: 583–590
Observations :

48. #3 Therapeutic effects of
Saccharomyces boulardii on mild residual
symptoms in a stable phase of Crohn's
disease
• Randomized, single-center, double-blind, placebo-controlled pilot study.
• 20 patients with established Crohn's disease suffering from diarrhea
and moderate complaints
• Treatment : Saccharomyces boulardii (S.b.) in a dosage of 250 mg t.i.d.,
initially for two weeks in addition to the basic treatment.
•
• Results: reduction in the frequency of bowel movements (5.0 ±1.4 vs. 4.1 ±
2.3 evacuations/day, p < 0.01)
•
Plein K, Hotz J Department of Gastroenterology, General Hospital of Celle. Zeitschrift fur Gastroenterologie [1993, 31(2):129-134]

49. • After this initial phase, the patients were allocated in randomized
order to the control group (n = 7) receiving placebo, or to the verum
group (n = 10) receiving S.b.(250 mg t.i.d.) for 7 weeks, while the
basic treatment was maintained.
• The group treated with S.b. showed a significant reduction in the
frequency of bowel movements in the tenth week.No adverse drug
events were observed.

50. #4 Lactobacillus rhamnosus GG in the
prevention of antibiotic associated
diarrhea in children
• Objective: efficacy of Lactobacillus rhamnosus (Lactobacillus GG) in
reducing the incidence of antibiotic-associated diarrhea.
• Study design: Two hundred two children between 6 months and 10 years
of age were enrolled; LGG, 1 × 1010 – 2 × 1010 colony forming units per
day, or comparable placebo was administered.
• Results:
• Twenty-five placebo-treated but only 7 LGG-treated patients had
diarrhea.
• Lactobacillus GG overall significantly reduced stool frequency and
increased stool consistency

51. • Conclusion: Lactobacillus GG reduces the incidence of antibiotic-
associated diarrhea in children treated with oral antibiotics for common
childhood infections.
Antonson, MD, Terri L. Hanner, RN, James V. Lupo, PhD, and Rosemary J. Young, RN, MS, THE JOURNAL OF PEDIATRICS
VANDERHOOF ET AL VOLUME 135,NUMBER 5

52. Products in the market

55. Composition
Film Coated tablet contains : Probiotic Mixture
• (L.sporogenes, Bifidobacterium lactis, Bifidobacterium bifidum &
L.rhamnosus GG) – 2 billion c.f.u
• Saccharomyces boulardii – 250/500 mg.
• Indications
• Diarrheal Illnesses in Adults as well as in Children
• Affordable choice in children affected with Rotaviral Diarrhea.
• Indicated for Irritable Bowel Syndrome in the Adults.

56. S.b. cells are resistant to gastric acidity, proteolytic degradation, and
antimicrobial drugs.
Probiotic mixture is effective in alleviating irritable bowel syndrome
symptoms.
Probiotic mixtures are beneficial for a range of health-related outcomes
Multi-strain probiotics appear to show greater efficacy than single strains.
Mixture using species with different effects against different pathogens
have a broader spectrum of action that a single provided by a single strain.
Multi-strain supplements are formulated to target specific health
conditions.
S.b. cells are resistant to gastric acidity, proteolytic degradation, and
antimicrobial drugs.
Probiotic mixture is effective in alleviating irritable bowel syndrome
symptoms.
Probiotic mixtures are beneficial for a range of health-related outcomes
Multi-strain probiotics appear to show greater efficacy than single strains.
Mixture using species with different effects against different pathogens
have a broader spectrum of action that a single provided by a single strain.
Multi-strain supplements are formulated to target specific health
conditions.
·Response of Human and Rat Small Intestinal Mucosa to Oral Administration of Saccharomyces Boulardii JEAN-PAUL BUTS. PAU BERNASCONI,
MARIE-PAULE VAN CRAYNEST, PAUL MALDAGUE, AND ROGER DF MEYER, Vol. 20, No. 2, 1986
A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention K. KAJANDER*, , K. HATAKKA*, T. POUSSA, M.
FA¨ RKKILA¨ § & R. KORPELA*, , – Aliment Pharmacol Ther 2005; 22: 387–394.
Benefits

57. *Note
Probiotics should not be taken by patients who have an impaired immune
system. These are those who have HIV/AIDS, cancer, and undergoing
chemotherapy.
Fungaemia is a rare complication of the administration of S. boulardii,
and it is reported only in severely ill patients in intensive care units,
mechanically ventilated, treated by broad-spectrum antibiotics with
central venous catheter, or in immunocompromised adult patients. No
fungaemia has been reported in otherwise healthy adults and children