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probiotic symposium
1. THE
Annual probiotic symposium
The Yakult India Microbiota and
Probiotic Science Foundation
3rd and 4th December
2016
Chennai -INDIA
Chennai 2016
MUGH MUGH
3. Role of Probiotics in GI
DISEASES”
Asso. Prof. Dr Aziz koleilat
Beirut Arab University
Makassed University General Hospital
Beirut –Lebanon
Makassed @pediatrics.org
drkoleilat@hotmail.com
Chennai 2016
PASPGHAN
PASPGHAN
6. Definition
Probiotics Live microorganisms that confer a health benefit on
the host when administered in adequate amounts.
Prebiotic Dietary substances that nurture specific changes in
the composition and/or activity of the GI microbiota
(favoring beneficial bacteria), thus conferring
benefit(s) upon host health.
Synbiotics Products that contain both probiotics and prebiotics.
(Fuller, 1989 ,Roberfroid 2000,Gibson et al. 200).
Chennai 2016
Adapted from Guarner F, Khan AG, Garisch J, et al.
Probiotics and prebioticsworld gastroenterology organisation
global guidelines, 2011.
7. Louis Pasteur
(1822 - 1895)
Metchnikoff Elie
(1848-1916)
Potential benefits of
Lactobacillus~125 yrs ago 1905: Concept of Probiotics
Chennai 2016
Tissier , In 1899
8. HISTORY
Fuller ,1989, defined probiotics as microbial supplements that
benefit the host animal by improving its intestinal microbial
balance*.
Strachan, in 1989 propagated The hygiene hypothesis.
*Martin H. Floch et al , 2001 , Nutrition
Parker, In1974 was actually the first to use the
term "probiotic." in the clinical sense in which it is
now employed.*
Gibson and Roberfroid ,in 1995 introduced the
concept of prebiotics. J Nutr 1995, 125: 1401-1412.
Isoulori ….in 1999 introduced Probiotics
concept as immunomodulators. (AAA&I).
*Martin H. Floch et al , 2001 , Nutrition .
**IMF (Infant Milk Formula)
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9. Probiotics
New England Journal of Medicine 2002
Not all probiotics have same effect or function
They are strain specific – with specific mechanism …..
• Can be used in combination Or each alone…..
Lactobacillus bacteria mainly in the small
intestine.
Bifidobacteria reside in the large intestine.
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Now, Genetically engineered species that secrete
immunomodulators ex.Lactococcus lactis
10. Probiotics
The MAPK pathway is a chain of proteins in the cell that
communicates a signal from a receptor on the surface of
the cell to the DNA in the nucleus of the cell.
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11. Function and Action of PROBIOTICS
Modulate intestinal
immune function
•Reduce pro inflammatory cytokines
•Promote telarogenic cytokines profile
•Increase secretory IgA
Promote epithelial cell
hemostasis
•Enhance barrier function
•Promote cyto protective responses
•Improve cell survival
•Increase mucin production
Neuromodulatory effects •Muco-opioid and canaobiod receptors
on epithelial cells
•Reduces visceral hypersensitivity and
stress responses via enteric nerve cells.
Block effect of pathogens •Reduce pathogens binding
•Decrease luminal PH
•Produce anti bacterial bacitrocin
Nutritional benefit • Assist in breakdown of un digestable food
to produce usable nutrientChennai 2016
Koleilat 2016 E -CRONICS
13. How Probiotics Work
Lumen
(Adapted )Fedorak RN and Madsen KL Inflamm Bowel Dis, 2004
Cristiano Pagnini et al PNAS 2010 107:454-459;
adapted
lamina propria
Enhanced barrier integrity
Anti microbial activity
Secretesbacitreocin,
defensins
Stimulation of an immune
response
---Increase IgA
Immunomodulatory action
Decrease TNF & INFג
secretion
Increase TGFβ &IL10
secretion
Induce T reg cell
Induce T cell apoptosis
Dendretic cell modulation
•Competitive exclusion of
bacteria (Translocation &
adhesion)
Nuclear factor-κB (NF-κB)
PROBIOTICS
Enhanced tight junction
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14. Different Actions of Probiotics
Action Species
Produce pathogen- inhibitory substances L. reuteri
L. rhamnosus GG
Inhibit pathogen attachment S. boulardii &
L. acidophilus
B.clausii
Inhibit the action of microbial toxins S. boulardii
Stimulate immunoglobulin A S. boulardii
L. rhamnosus GG
Trophic effects on
intestinal mucosa
S. boulardii
Gary W. Elmer Am J Health-Syst Pharm 2001
Expert Review Gastroenterology &Hepatology
Prevention of barrier gut impairment B clausi
16. Probiotic influence on different immune functions
Immune system effect Organism
Increased phagocytosis
capacity
L. acidophilus (johnsonii) La1L. casei
B. lactis Bb12B. lactis HN019
L. rhamnosus GG L. rhamnosus HN0
Increased NK cell activity
L. Rhamnosus HN001
B. lactis HN109
L. casei subsp. casei + dextran
Stimulation of IgA production
• B. bifidum
• L. acidophilus (johnsonii)
• La1L. casei rhamnosus GG
• B. lactis Bb12
Suppression of lymphocyte
proliferation Induction of
apoptosis
L. rhamnosus GG L. casei GG B. lactis
L. Acidophilus L. delbrueckii subsp. bulgaricu
S. thermophilus
L. paracasei E. coli Nissle 1917
Increased cell- mediated
immunity
L. casei Shirota
V. Delcenserie 2008 curr,Issues Mol Chennai 2016 (Loris R 2016 Expert Review G&H.)
18. Probiotics Improve NAFLD in Obese Children and
Adolescents
Famouri, Fatemeh; Shariat, Zainab; Hashemipour, Mahin; Keikha, Mojtaba; Kelishadi, Roya
Journal of Pediatric Gastroenterology and Nutrition November 03, 2016
A probiotic compound containing Lactobacillus acidophilus,
Bifidobacterium lactis, B. bifidum, and L. rhamnosus was
found to be effective in reducing biochemical and sonographic
features of NAFLD in obese children.
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Non-alcoholic fatty liver disease (NAFLD)
• There was a significant decrease seen in serum
alanine aminotransferase and aspartate
aminotransferase, as well as a decline in mean
cholesterol, LDL-C, and triglycerides
19. Probiotic and Synbiotic Therapy in Critical Illness
William Manzanares; Margot Lemieux; Pascal L. Langlois; Paul E. Wischmeyer
Crit Care. 2016;20(262)
Chennai 2016
o Critical illness is characterized by a loss of commensal flora and an
overgrowth of potentially pathogenic bacteria, leading to a high
susceptibility to nosocomial infections
Probiotics significantly reduced the incidence of infectious
complications, including new episodes of VAP(Ventilator-associated
pneumonia )in critically ill patients.
o In the largest systematic review and meta-analysis of probiotics to date,
in 30 trials enrolling 2972 patients
Probiotics protect the gut barrier, attenuate pathogen overgrowth,
decrease bacterial translocation and prevent the infection.
Probiotic therapy with L. plantarum currently
demonstrates the most significant effect on the
reduction of infections..
(Klarin 2005 McNaught 2005 Klarin 2008)
*(William Manzanares 2016)
20. Lactobacillus acidophilus modulates intestinal pain and
induces opioid and cannabinoid receptors.
Rousseaux C, Thuru X, Gelot A et al.Nat Med 2007;13:35–37.
Abstract
• Abdominal pain is common in the general population and, in
patients with irritable bowel syndrome, is attributed to visceral
hypersensitivity.
• Oral administration of specific Lactobacillus strains induced the
expression of mu-opioid and cannabinoid receptors in
intestinal epithelial cells, and mediated analgesic functions in
the gut-similar to the effects of morphine.
Rousseaux C. Nat Med.2007
David B 2016 . Chennai 2016
These results suggest;
That the microbiology of the intestinal tract influences
our visceral perception,
That new approaches for the treatment of abdominal
pain and irritable bowel syndrome.
(Marilla Carabotti et al 2015)
21. Chennai 2016
Marilla Carabotti et al (2015) Ann Gastroenterol. Apr-Jun; 28(2): 203–209
Mary Sanders (2010)Academy of science new york
Koleilat (2016) EC Pediatrics 2.4:190-200
The gut-brain axis: interactions between enteric
microbiota,
central and enteric nervous systems
Annals of Gastroenterology (2015) 28, 1-7
Marilia Carabottia, Annunziata Sciroccoa, Maria Antonietta Masellib, Carola Severia
University Sapienza, Rome; S. De Bellis, Castellana Grotte, Bari, Italy
23. Clinical application of probiotics
in gastroenterology
Potential applications of probiotics for prevention and/or treatment of a
large number of gastrointestinal disorders, including: in use already.
Rota associated diarhea( Vanderhoof, J Pediatr 1999; (G Grandy 2010 BMC ,Marteau
PR, de Vrese M, Cellier CJ, Schrezenmeir JAm J Clin Nutr. 2001)
Antibiotic-associated diarrhea, (Szajewska ET al.JPGN 2001; Fang Yan cur opn 2010)
Infantile diarrhea. (Guandalini et al., JPGN, 2000)
IBD, (Rahimi R Dis Sci 2008,Pronio inf Bowel dis 2008)
IBS,(Quigly Jclin gast2008,HovevdaBMC2009)
Neonatal necrotizing enterocolitis (NEC),(CaplanJ Pein.2009)
Enteropathy in HIV infection, (MartinezCan J Micro 2009)
Fang Yan; David Brent Polk; Probiotics: progress toward novel therapies for intestinal diseases
Curr Opin Gastroenterol. 2010;26(2):95-101.
By down regulation amiloration , adjuvents, or synergisim
Chennai 2016
24. Chennai 2016
Diseases that have been reportedly treated with probiotics
include:
Allergy ,atopic Eczema (Isoulori 201
Obesity (Sean Davies et al , the Journal of Clinical Investigation, 24 June 2014
Intestinal pain (Rousseaux C .Nat Med.2007 )
Gluten intolerance, gastroenteritis, (Smecuol E 2013)
Helicobacter pylori infection, (Lesbros-Pantoflickova - 2007j.n) (Loris R 2016
Expert Review G&H.)
Colon cancer.(abdekrazak Arch Pediatr Adolesc Med. 2012,2013)
Clinical application of probioticsIn
gastroenterology
By:
Inflammation degradation ,
Immune boosting.
KOLEILAT. Probiotics Nowadays EC Paediatrics2.1(2016):100-107
25. Proposed use of probiotics in
gastroenterology
Radiation induced diarrhea .
(P.Delia,et al ,Use of probiotics for prevention of radiation-induced diarrhea World J
Gastroenterol. 2007)
Constipation .
(Dimidi E ,Christodoulides et al The effect of probiotics on functional constipation in
adults: a systematic review and meta-analysis of randomized controlled trials. Am J
Clin Nutr. 2014 )
Infantile colic.
(E bennett 2014 bmj probiotics and infant colics )
Dental Caries and Periodontal Disease .
(Amit Bhardwaj, Shalu V Bhardwaj Role of Probiotics in Dental Caries and Periodontal
Disease Arch Clin Exp Surg. 2012)
Cardiovascular diseases .
(RajivSaini, et al 2010 J Cardiovasc Dis : potential of probiotics in controlling cardio vascular
diseases )
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28. Use of Probiotics for Management of Acute
Gastroenteritis:
A Position Paper by the ESPGHAN Working Group
for Probiotics and Prebiotics
Hania Szajewska,
on Behalf of the ESPGHAN Working Group for Probiotics and
Prebiotics
January 2014 - Volume 58 - Issue 1
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29. …
General Comments
• Adjunct to rehydration therapy reduced the duration of diarrhea
• Strain specific In efficacy and safety .
• The safety and clinical effects should not be generalized….
• A lack of evidence regarding the efficacy of a certain probiotic(s) does not
mean that future studies will not establish health benefits.
• The efficacy has to be confirmed in well-conducted RCTs,*
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*RCT-Randommised clinical trial
The efficacy of specific strains at a specific dosage
in a specific setting are not sufficient evidence to
support the presence of health effects at a lower
dosage and in a different setting.
30. Probiotics in gastrointestinal
disorders
The precise mechanism's of action of probiotics has not thus far been
clarified.
o Potential mechanisms to consider include:
Modulation of GI immunity by:
altering inflammatory cytokine profiles
down regulating pro inflammatory cascades
inducing regulatory mechanisms in a strain-specific manner;
Inhibiting pathogenic bacterial adherence;
Acidification of the colon by nutrient fermentation;
Enhancement of epithelial barrier function;
Induction of opioid and cannabinoid receptors in intestinal epithelial cells;
Reduction of visceral hypersensitivity, spinal afferent traffic, and stress
response
(Elizabeth C. 2010,Rousseaux C..2007 ) .
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Elizabeth C. Et a lTherap Adv ،Gastroenterol.2010
31. Action of Probiotics in gastrointestinal disorders
• Probiotics have intestinal barrier, immunologic, antibacterial, and motility
and sensation effects that may contribute to their efficacy in various
indications (Ohland CL2010 )
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Have direct effects affect the intestinal mucosa &epithelial
barrier by:
Increasing mucin expression/secretion by goblet cells .
Augmenting production of antimicrobial peptides, including β-defensin;
Enhancing tight junction stability decreasing epithelial permeability to
intraluminal pathogens and toxins. (Ohland CL2010 )
Influence mucosal immunity by :
Increasing levels of IgA-producing cells in the lamina propria
Promoting secretion of secretory IgA into the luminal mucus layers,
limit epithelial colonization by bacteria.
32. Action of Probiotics in gastrointestinal disorders
Influence cytokine expression and suppress mucosal inflammation,
potentially through Toll-like receptor signaling (deRoock 2010).
Attenuate post infectious intestinal dysmotility (, Lactobacillus
paracasei (VerduEF 2004)
Prevent and reverse dysmotility associated with intestinal infection.
(Collins et al. 2009)
Alleviate visceral hypersensitivity (KamiyaT 2006 ), by induction of
expression of cannabinoid and opioid receptors on intestinal cells .
Toll-like receptor
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33. • Recommendations for Probiotic Use in
Humans
• Martin H. Floch, MD* and W. Allan Walker, MDw
J Clin Gastroenterol. 2015 Nov-Dec;49 Suppl 1:S69-73.
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34. J Clin Gastroenterol. 2011 Nov;45 Suppl:S168-71. doi:
10.1097/MCG.0b013e318230928b.
Recommendations for probiotic use-2011 update.
Floch MH1, Walker WA, Madsen K, Sanders ME, Macfarlane GT, Flint HJ, Dieleman LA,
Ringel Y, Guandalini S, Kelly CP, Brandt LJ
Chennai 2016
The use of probiotics and ingestion of
expressed maternal breast milk containing
probiotics can help to stabilize
colonization and to reduce the incidence
and severity of NEC when given to
premature infants at risk. (Floch,Walker
2011)
Recommendations for Probiotic Use in Humans—A 2014 Update
Necrotizing Enterocolitis
•Bifidobacterium breve BBG-001 failed to prevent NEC
in very preterm infant
• kate Costeloe et al , Lancet 2016 Feb 28;387(10019):649-60. Epub 2015 Dec 28.
Daniells 2015)
35. Recommendations for Probiotic Use in Humans—A 2014 Update
Childhood Diarrhea
The microbiota is maintained in a stable ecology, and it appears that
probiotics are very helpful in shortening the course of acute
gastroenteritis diarrhea [Szujewsku H.2007. Guandalini S. 2008].
• There are numerous studies to establish this.
Chennai 2016
Reduction of diarrhea duration of little
more than 1 day, and to be exerted mostly
on diarrhea due to rotavirus.
The effect is strain-dependent, and dose-
dependent, with doses of at least 10
billion/d being necessary.
It is clear that starting Saccharomyces boulardii, LGG, or strains of
Lactobacillus reuteri are extremely helpful in shortening the course of
the diarrhea [Szujewsku H.2007. Guandalini S. 2008].
36. Recommendations for Probiotic Use in Humans—A 2014 Update
Antibiotic-associated Diarrhea
Probiotics are helpful in the prevention of C. difficile- associated diarrhea
in both adults and children. [Goldenberg 2013, Cochrane Database ] .
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FMT will be used used for the cure and
prevention of resistant C. difficile diarrhea in
the coming years.
66% lower infection rate when they received prophylactic probiotics with
multispecies probiotics products ,with single-species products reduced the
risk by 50%. Johnston 2012
The development of fecal microbial transplantation
(FMT) proved that it can cure and prevent resistant C.
difficile infection . (Garborg K. 2010,Floch
2012,Hamilton 2012)
S. boulardii, LGG, in combinations [Floch
2011] are helpful in accomplishing this
outcome in antibiotic-associated diarrhea
37. Recommendations for Probiotic Use in Humans—A 2014 Update
Inflammatory Bowel Disease
• Pouchitis can be prevented, and remission can be
maintained with the use of the probiotic VSL#3[Mimura T.2004].
Therapy reports , ProbioticsVSL#3( Escherichia coli Nissle, S.
boulardii and LGG; )was most successful [Miele E.2009).
• Regulate dysbiosis that occurs in simple ulcerative colitis [Floch 2012].
• Dysbiosis, which is seen with C. difficile, can be corrected in
selective ulcerative colitis patients and reduce symptom control By
FMT [Brace C.2014]
This is the same dysbiosis that is treated with FMT.
Chennai 2016
Feacal transplant
VSL#3 was the most effective in
ulcerative colitis,
less of an effect in Crohn’s disease
which does not respond as well [Shen J.,
2014].
38. Feacal transplant !!!!!!
• FMT permits the administration of over 500 strains of human organisms.
• They certainly fit the definition of a probiotic in that they are human
organisms administered to benefit health.(Floch 2012)
• There are many papers in the literature that demonstrate a probiotic —
namely, VLS#3—which is effective in ulcerative colitis, pouchitis, and
Irritable Bowel Syndrome.(Guandalinni S 2010)
It enables total biological stimulation of the
immune system and seeding of the host basic flora
for fermentation use, and possibly contains selective
therapeutic inhibition substances such as
defensins.
Koleilat : Fecal microbiota transplantation Review CRNSS Update series october 2016:1-9Chennai 2016
39. Recommendations for Probiotic Use in Humans—A 2014 Update
Irritable Bowel Syndrome (IBS)
• IBS is a major international clinical problem.
Bifidobacterium infantis B5624 (Ireland) has given the best reports
for relief of symptoms ” with good rating [Groeger D., 2013].
– Lactobacillus plantarum and Bifidobacterium animalis on
human IBS [Guyonnet D., 2007].
– Probiotics mixtures, including Lactobacillus acidophilus, L.
plantarum, Lactobacillus rhamnosus, Bifidobacterium breve,
Bifidobacterium lactis, Bifidobacterium longum, and
Streptococcus thermophilus were used. (Cha 2013) RCT
•
Chennai 2016
Effect on probiotics on IBS still remains controversial.
Enteric nerve cells
Act on stabilization and
immunomodulatory effect on the
intestinal microbiota and mucosa
Decrease irritability via enteric nerve cells
in the lumina properia. (Groeger D., 2013].
40. Helicobacter Pylori Infection
• The presence of clarithromycin-resistant H. pylori, eradication is
significantly attenuated. (Ushiyama et al.2003)
Lactobacillus gasseri inhibited both the in vitro growth of
clarithromycin-resistant H. pylori and the release of interleukin-8 from
epithelial cells, H. pylori colonization was significantly decreased by L.
gasseri.[Ushiyama et al.2003 ]
Induce inhibition of H. pylori growth and adhesion to
epithelial cells and an effect on the host immune system.
Modify eradication rates and antibiotic-associated
gastrointestinal side effects.[Hamilton-Mille2003]
Probiotic-
Probiotics have been suggested to increase efficacy of
eradication therapy by:
preventing antibiotic-associated side effects and thus
increasing compliance.
significantly lower incidence of antibiotic-associated
diarrhea and taste disturbance (Bacillus Clausii ). [Cremonini F
2002] (Loris et al 2016 Expert Rivew G&H )
41. Probiotics useful in Celiac
Disease
Probiotics :Lactobacillus and Bifidobacterium(Desousa 2014 Clin Microbiol Rev).
• Alter intestinal microbiota composition and fermentation derived
metabolite by :
regulating epithelial cell barrier function
modulating immune response (Licciardi PV et al 2002 , Gut Pathol.2-24 )
• Dietary changes help alleviate the severity of celiac disease for some
patient, ameliorate inflammation to a varying degrees ,(Collado et al2008)
Chennai 2016
Synbiotics :manipulate the intestinal
microbiota and could improve the
quality of life for celiac patients
,especially on associated disease such
type 1 diabetes and other autoimmune
disorders (eczema herpitiforme )
(RossiMet al 2010 journal of Leukocyte Biology 87:749-751)
42. Probiotics & Pancreatitis
• The safe use of probiotics are raised by the outcomes of several clinical
trials.( Ridwan 2008 )
– A mixture of six probiotic bacteria (L. acidophilus, L. casei, L.
salivarius, L. lactis, B. bifidum, and B. infantis) used to treat patients
with severe acute pancreatitis ,
Increased their risk of mortality ,!!!!!!
– although this bacterial mixture inhibited the growth of most
pathogens that caused pancreatitis complications in the preclinical
animal studies. (Snydman 2008 Clin Infect Dis)
Chennai 2016
43. Lactose intolerance
• Application of pre- and probiotics to improve the clinical symptoms of
lactose intolerance
Lactobacillus delbrüeckii in a milk product can deliver β-galactosidase
activity.
Lactobacillus bulgaricus and Streptococcus thermophiles alleviate the
lactose intolerance through their enzyme lactase when the product
reaches the intestinal tract.
• lactose intolerance can be reduced by β-galactosidase enzyme of the
lactic acid bacteria which present in them. ( Masood et al. 2006)
(Roel J. Vonk 2012)
Chennai 2016
Meta-analysis show inconsistent results
(Levri et al. J Fam Pract 2005)
Benefit remains unproven.
Probiotics have an effect by two levels:
1.The Hydrolysis of lactose in the milk product
2.The hydrolytic capacity of probiotic to reduce the actual amount of lactose
44. Probiotics and Hepatic
Encephalopathy
Probiotics (VSL#3 or lactobacillus species.)are more effective than
placebo in;
– Reducing hospitalizations among cirrhotic patients,
– Improving MHE, (minimal hepatic encephalopath)
– Preventing progression of MHE to OHE. (overt HE)
• Probiotics appear to have similar effectiveness to lactulose in regard to
these outcomes.
• The potential role of probiotics in the treatment of minimal hepatic
encephalopathy in patients with cirrhosis.”still in research.
Chennai 2016
S Saab et al2016
45. Other GI Disorders
Collagenous Colitis:
Possible benefit of E.coli Nissle 1917 (Tromm et al. Z Gastroenterol 2004)
Placebo-controlled trial: Combination of Lactobacillus acidophilus
and Bifidobacterium animalis caused improvement in symptoms
but had no significant effect on primary endpoints (Wildt et al.Inflamm
Bowel Dis 2006)
.
Diverticular Colitis:
Combination of VSL#3 and an oral
beclomethasone Mezalamine ,was beneficial in
a case serie .(Tursi et al. 2008,floch etal2013)
Chennai 2016
Meta- analysis Cochrane Database Syst Rev.
2008 : No evidence for the effectiveness
probiotics!!!!!!!!!!!Alone …..
46. Summary
• Probiotics are a therapeutic class being increasingly used for a
variety of GI disorders.
• Probiotics appear to alter intestinal microflora and may exert
their effect's) by a variety of mechanisms.
• Many species of probiotics exist and it is generally accepted that
all probiotics are not created equal.
• Efficacy may be due to a single strain or multiple strains or a
combination of different probiotics.
• Probiotics do not provide additional benefit compared with
standard therapy alone.
.
Chennai 2016
48. • Dr Amal Nous MD
--Makassed University General Hospital
Clinical lecturer
Beirut Arab University Beirut, Lebanon
• Dr Dania Tabash
– MGH chief resident ,Pediatric Department
• Miss Lubna Sino
– Secretary research Department
Chennai 2016
50. THE ANNUAL MEETING
Pan Arab Societies Pediatric Gastroenterology ,Hepatology
& Nutrition
PASPGHAN- 2017
Beirut -Lebanon
General secretary of PASPGHAN Prof. Nezha Mouane (Morocco )
President of the congress Asc.Prof Aziz Koleiat( Lebanon )
SEPTEMBER 2017
Chennai 2016
51. Dr Aziz Koleilat
Associate professor Beirut Arab University
Makassed University General Hospital
Pediatric gastroenterology and Nutrition& Asthma
IBR member
GINA Meditrenian group ,
lebanon representative
Vice general secretary PASPGHAN
Pan Arab Society,Pediatric Gastro Enterology Hebatology & Nutrition .
drkoleilat@hotmail.com
009613231717 (Skyp. Whatsup)
Chennai 2016
MUGH
52. Criteria for use a probiotic
• It must be safe for consumption:
– Not pathogenic or carrying antibiotic resistance genes
– Not degrading to intestinal mucosa or conjugating for bile
acids
• It must survival intestinal transit: Acid and bile tolerant
• It must adhere to mucosal surface and colonize the intestine
(at least briefly,)
• Produce antimicrobial substances and antagonize pathogenic
bacteria
• At least one phase 2 study documenting benefit.
• It must be stable during processing and storage…….
(Borchers et al. 2009)
Chennai 2016
53. Misconception with probiotics
• All probiotic supplements are basically the same.
• Could have different effects on health.
• Can replace medications.
• Food and supplement labels provide accurate microbe counts.
• Yogurts are generally a good source of probiotics.
• The More Strains The merrier and better .
• The Higher the Number of Billions, the Better.
• The Best Probiotics are Kept in the Fridge.
• lyophilisation ensure that the probiotics remain viability at room
temperature.
• Probiotics may not be used while taking antibiotics Course.
www.livescience.chelp probiotics-myths.html 2014
Chennai 2016
54. COLONIZATION
• A common misconception is that probiotics must always colonize the
intestinal tract to exert their effects.
• Some probiotics (e.g., Bifidobacterium longum and Bacteroides
thetaiotamicron) become part of the human intestinal microflora,
whereas others (e.g., Lactobacillus casei and B. animalis) may not .
• Non colonizing probiotics indirectly exert their effects either in a transient
manner as they pass through or, more likely, by remodeling or influencing
the existing microbial community .
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55. Infection:
• Infective endocarditis or bacteremia (Extremely rare-) represent
0.05% -0.4%
• liver abscess caused by lactobacillus rhamnosus (500 ml/d).
Recovered with surgical drainage and antibiotics.
.
Safety of using probiotics
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Review of 200 cases of lactobacillus infection 1950-2003;
114 cases of bacteremia*
Mortality rate 32%
All patients had significant morbidity including
malignancy
62 cases of endocardidtis with 22.9% mortality rate.
(Cannon et al. Eur J Clin Microbiol Infect Dis 2005.)
56. Safety PROBIOTICS
disadvantages Kelli Cooper 2013
• Metabolic and enzymatic effect :theoretically may have some
effect on metabolism of bile salts and mucous. (not reported
yet )
• Immunological effects : when we have immunodeficient
patient and ingest large amount of certain probiotics cause
relapse of autoimmune reactions.
• Gene transfer: if genetically modified probiotics used may
harbor antibiotic resistant genes.
Risk is transferring of antibiotic resistance genes to the host,
as L. reuteri and L. plantarum have been found to carry such
genes. (Egervarn MJ Appl Microbiol. 2009)
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57. Chennai 2016
The use of probiotics during pregnancy, in neonates, and in
children has not been associated with any adverse
immunologic effects,(SrinivasanJ Pediatr Gastroenterol Nutr 2006)
Safety PROBIOTICS
disadvantages Kelli Cooper 2013
Infection : when probiotics, given to persons with
severe underlying disease, may cause systematic
infection.
Bacteremia and fungemia , occurrence in ill
patients and immuno deficient individuals has
also been reported . (Roy M Robins 2006)
Bacteremia reported in premature babies with
short-gut syndrome (Hala fatima 2010)
58. Dosage
Recommended Dosage for Probiotics
• Different brands of probiotics can contain anywhere from one to 10 billion
colony-forming units or CFUs.
• To maintain a healthy digestive tract, a probiotic with one to two billion
CFUs is recommended.
• However, if you are taking antibiotics, or if you have symptoms of a
bacterial imbalance such as diarrhea, you can take a probiotic with up to
10 billion CFUs until the problem clears up.
• To maintain microorganism balance, take a probiotic of one to two billion
CFUs daily or every other day.
• To correct a problem, probiotics containing 10 billion CFUs can be taken
daily for up to two weeks. -
Updated: Apr 21, 2015 | By Beverly Bird
Chennai 2016
59. Dose of probiotics for neonates
• The probiotic supplementation in infants should be done carefully,
especially those who are preterm because preterm of impaired immune
system, poor nutrition, and frequent exposure to harmful microorganisms.
• Recommended
- Neonates (less than 32 weeks age of gestation): 3 x 109 cfu/day
- Extremely low birth weight infants: 1.5 x 109 cfu/day until they reach
enteral feeds of 50-60 ml/kg/day
- The probiotic dose should be diluted in 1.0 to 1.5 mL of breastmilk or water.
Health and medicine dr Rega 2013 Chennai 2016
60. Facts about Probiotics
• Not all Probiotics have same action and functions
• Probiotics are specific strains
• Probiotics are not absolute treatment , mainly adjuvant , ameliorate
inflammation
• There are side effects for probiotics , fungioma , carditis
• Probiotics absolutely not effective in pancreatitis
• Probiotics are not a treatment for asthma
2015
Chennai 2016
61. Chennai 2016
Interestingly, reduced microbial diversity was associated
with diseases such as Crohn’s disease [Manichanh et al.
2006] and eczema in early life. [Forno et al. 2008]
62. As with diseases
• Most probiotics tested to date are more effective than
placebo in inducing or maintaining IBD remission
• There is good evidence to support the efficacy of S. boulardii
and LABs and the combination of the two for AAD, VSL#3 for
pouchitis, and B. infantis 35624 for IBS.
• Probiotics decrease the duration of symptoms in acute
infectious diarrhea.
• Probiotics, including E. coli Nissle 1917, LGG, and VSL#3 are
as effective as standard therapy (mesalamine) in inducing or
maintaining remission in UC or CD. When added to standard
therapy,
Chennai 2016
Summary
.
Need to be evaluated
AAD-Antibiotic associated diahrea
63. As with safety
• Probiotics have been shown to be safe in immunocompetent hosts in an
outpatient setting.
• Administration of probiotics to immunocompromised, chronically ill,
hospitalized patients with GI disorders, and indwelling catheters may
predispose to probiotic sepsis, probiotics may increase translocation of
bacteria into the bloodstream.
Chennai 2016
Summary
64. What MUST be finally resolved
• Optimal doses,
• Duration of treatment,
• Comparison of different strains and different probiotics,
• Single versus combination probiotics,
• Combination of probiotics with prebiotics,
• Efficacy of various probiotics in different disease states,
• Safety of probiotics in debilitated patients
• Safety in patients with compromised gut epithelial integrity
Chennai 2016
