Ore and probiotics

1. PROBIOTICS, SYNBIOTICS AND
PREBIOTICS
PRESENTER- Dr. Kuldeep Singh
MODERATOR- Prof. Afzal Azim

2. INTRODUCTION
 The total number of human cells is approximately 3.0·10
13
while the number of microorganisms inhabiting humans is
approximately 3.8·10
13
.
 Most of the microbiota colonizes the gut establishing a
symbiosis with their host.
 The gut microbiota of a healthy subject harbors all three main
life domains: bacteria, archaea, and eukarya.
 There are six known bacterial phyla. Firmicutes and
Bacteroidetes are the most abundant, followed by
Actinobacteria and Proteobacteria .

3. INTRODUCTION
The large intestine is the most densely populated habitat due to the
slow transit time and the availability of fermentable substrates.

4.  The gut microbiota composition varies among individuals,
changing throughout life due to intrinsic factors like age and
genetics and extrinsic modifiable factors like diet environment,
and drug use.
 In the intensive care unit (ICU), patients are subjected to
antibiotics, gastrointestinal transit changes, nutritional changes,
and sepsis , collectively leading to a gut microbiota imbalance,
namely dysbiosis, whose most common symptom is diarrhea .
 Ninety percent of the intestinal microflora is lost within 6 h of
ICU admission .
 ICU patients have lower bacterial diversity and variability, and
opportunistic pathogens are enriched over symbiotics

5. The shift from microbiota to pathobiota in the ICU is driven by antibiotics and ICU-
speciic treatments like artiicial feeding, mechanical ventilation, proton pump
inhibitors, vasopressors, and opioids.
Corriero et al. Critical Care (2022) 26:379

6. Potential personalized approach for treating dysbiosis in ICU patients

7. WHAT ARE PROBIOTICS?
 The term “probiotic” comes from Latin “pro”
and the Greek “bios”, together meaning “for
life.”
 Probiotics are defined as “live microorganisms
that, when administrated in adequate amounts,
confer a health benefit on the host”.
 © 2019, International Scientific Association for Probiotics and
Prebiotics

8. HISTORY
 Probiotics were first conceptualized over a
century ago by Elie Metchnikoff.
 Metchnikoff was the first to introduce the idea
that consuming live microbes may be beneficial
to health. He suggested that it is possible to
replace harmful microbes in the gut microbiota
with beneficial ones.

9. HISTORY
 During an outbreak of shigellosis in 1917, the German
professor Alfred Nissle isolated a strain of Escherichia
coli from the feces of a soldier unaffected by the
disease. This strain, named E. coli Nissle 1917, was later
used to help prevent acute gastrointestinal
salmonellosis and shigellosis.
 In 1930, the Japanese microbiologist Minoru Shirota
subsequently Lacticaseibacillus paracasei strain Shirota.
These efforts led to the first commercially marketed
fermented dairy drink. It was marketed as Yakult starting
in 1935 and continues to be manufactured and sold
worldwide today.

10. PROBIOTICS
 The most common are species of Bifidobacterium
(adolescentis, animalis, bifidum, breve and longum)
or Lactobacillus (acidophilus, casei, fermentum,
gasseri, johnsonii, paracasei, plantarum, Rhamnosus
and salivarius).
 Saccharomyces Boulardii (a yeast).
 Newly identified human commensals associated with
healthy intestines may comprise probiotics of the future.
Such microbes include Akkermansia muciniphila,
Faecalibacterium prausnitzii, Roseburia spp. and
Eubacterium hallii.

11. MECHANISM OF ACTION
O’Toole and Cooney (2008)

12. Rijkers (2010)

13. EFFECTS OF PROBIOTICS
MOLECULAR-
 Produces nutrients and antioxidants
 Produces growth and coagulation factors
 Activates the MALT system
 Modulates Th1/Th2 response
 Promotes antioxidant actions
 Controls potentially pathogenic microorganisms
 Reduces production of endotoxins
 Reduces mutagenicity

14. EFFECTS OF PROBIOTICS
HUMORAL-
 Stimulates IgA production
 Inhibits IgE production
 Stimulates NO production
 Modulates cytokine response
CELLULAR-
 Stimulates macrophage function
 Stimulates NK cell activity
 Promotes growth and regeneration
 Promotes apoptosis

15. POTENTIAL USES
 Prevention of antibiotic-associated diarrhea.
 Management of some mild to moderate digestive
symptoms associated with irritable bowel syndrome or
functional bowel conditions.
 Reducing symptoms associated with lactose
maldigestion.
 Reducing colic symptoms and eczema in infants,
 Treating infectious diarrhea.
 Decreasing common infections of the respiratory tract,
gut, or vaginal tract.

16. PREBIOTICS-HISTORY
 The concept of a ‘prebiotic’ was put forward in 1995 by
Gibson and Roberfroid in their scientific publication
called “Dietary modulation of the human colonic
microbiota: Introducing the concept of prebiotics”.
 In the decades that followed, scientific discussions
about prebiotics tended to focus on identifying
substrates that target health-promoting groups of
bacteria in the gut: usually, bifidobacteria and
lactobacilli.

17. PREBIOTICS- DEFINATION
 The most defination recent was agreed at the 2010
Meeting of the International Scientific Association of
Probiotics and Prebiotics (ISAPP).
 “A dietary prebiotic is a selectively fermented
ingredient that results in specific changes, in the
composition and/or activity of the gastrointestinal
microbiota, thus conferring benefit(s) upon host
health.”
 (Gibson et al., 2011).

18. PREBIOTICS
 “A substrate that is selectively utilized by host
microorganisms conferring a health benefit”.
 Thus, the concept includes three essential parts: a
substance, a physiologically beneficial effect, and a
microbiota-mediated mechanism.
 A prebiotic compound must confer a beneficial
physiological effect on the host and that effect should
derive at least in part from utilization of the compound
by resident microbes.

19. PREBIOTICS
 The most commonly-studied prebiotics are the soluble
fibers inulin, fructooligosaccharides (FOS),
galactooligosaccharides (GOS), and more recently
human milk oligosaccharides (HMOs).

20. PREBIOTICS
 At present, there are no official dietary
recommendations for ‘adequate intake’ or
‘recommended daily allowance’ for prebiotics in healthy
individuals.
 Most prebiotics for the gut require an oral dose of at
least 3 grams per day or more to confer a benefit.
Typically, around 5 grams is the target for FOS and GOS
in the daily diet—and this includes dietary sources of
prebiotics.

21. CRITERIA FOR PREBIOTIC SELECTION
 The prebiotic concept is based on the selective
stimulation of the host’s own beneficial
microbiota.
 It is essential to measure the effect of the
candidate prebiotic on bacterial growth; it is
not enough simply to know that fermentation
has taken place.
 The main site of action for prebiotics is the
colon. Thus, a prebiotic should resist the effects
of gastric acidity and digestive enzymes in
order to reach the colon intact..

22. Prebiotics must be selectively utilized and have adequate evidence of health benefit for
the target host. Dietary prebiotics must not be degraded by the target host enzymes.
CLA, conjugated linoleic acid; PUFA, polyunsaturated fatty acid; FOS,
fructooligosaccharides; GOS, galactooligosaccharides; MOS, mannanoligosaccharide; XOS,
xylooligosaccharide.

23. SYNBIOTICS-DEFINATION
 • “A mixture comprising live
microorganisms and substrate(s)
selectively utilized by host
microorganisms that confers a health
benefit on the host”.
 Within this definition, ‘host’ microorganisms comprise
both autochthonous (resident or colonizing the host)
and allochthonous (externally applied, such as
probiotics) microorganisms, either of which can be
targets for the substrate contained in the synbiotic.

24. SYNBIOTICS
 Two subsets of synbiotics were defined:
 A ‘complementary synbiotic’ is a synbiotic composed of
a probiotic combined with a prebiotic, which is designed
to target autochthonous microorganisms.
 A ‘synergistic synbiotic’ is a synbiotic in which the
substrate is designed to be selectively utilized by the co-
administered microorganism(s).

26. DESIGN AND MECHANISMS OF ACTION OF
COMPLEMENTARY AND SYNERGISTIC SYNBIOTICS.

27.  Living microorganisms used to prevent dysbiosis
 Antimicrobial properties, positive impact on immune system,
reduced gut cell death
 Seems to reduce infections (especially VAP and C. diffcile infections)
and antibiotic consumption in critically ill patients
 Discordant mortality results
 Potential side-efects: sepsis, bacteremia, endocarditis, abscesses,
VAP

28. Thirty trials that enrolled 2972 patients were identified for
analysis. Probiotics were associated with a significant
reduction in infections (risk ratio 0.80, 95 % confidence
interval (CI) 0.68, 0.95, P = 0.009; heterogeneity I 2 =36%, P =
0.09). Further, a significant reduction in the incidence of
ventilator-associated pneumonia (VAP) was found (risk ratio
0.74, 95 % CI 0.61, 0. 90, P = 0.002; I 2 = 19 %). No effect on
mortality, LOS or diarrhea was observed. Subgroup analysis
indicated that the greatest improvement in the outcome of
infections was in critically ill patients receiving probiotics
alone versus synbiotic mixtures, although limited synbiotic
trial data currently exists.

34.  Study demonstrated that in 30 trials enrolling 2972
patients, probiotics significantly reduced the incidence
of infectious complications, including new episodes of
VAP in critically ill patients.
 Probiotic therapy with L. plantarum currently
demonstrates the most significant effect on the
reduction of infections.

35. 33 studies were included in this systematic review and meta-
analysis, with 4065 patients who received probiotics or synbiotics
(treatment group) and 3821 patients who received standard care or
placebo (control group).
The pooled data from all included studies demonstrated that the
treatment group has significantly reduced incidence of
ventilation-associated pneumonia (VAP).
There were no significant differences in diarrhea, CDI, incidence of
hospital acquired pneumonia, and in hospital mortality between
the two groups.

38. CONCLUSION AND LIMITATIONS
 This systematic review and metaanalysis supports the
potential role of probiotics or synbiotics in reducing the
incidence of VAP and sepsis, as well as the duration of
mechanical ventilation, length of hospital stay, length of
ICU stay, and ICU mortality in critically ill patients.
 However, limitations of this study include small sample size,
personal equation in the process of data extraction, and
different composition and dosage of the intervention.

39.  Johnstone et al.
 Prevention of Severe Pneumonia and Endotracheal Colonization Trial
(PROSPECT)
 OBJECTIVE - To evaluate the effect of Lactobacillus rhamnosus GG on
preventing VAP, additional infections, and other clinically important
outcomes in the intensive care unit (ICU).
 DESIGN, SETTING, AND PARTICIPANTS Randomized placebo-
controlled trial in 44 ICUs in Canada, the United States, and Saudi
Arabia enrolling adults predicted to require mechanical ventilation for
at least 72 hours. A total of 2653 patients were enrolled from October
2013 to March 2019 (final follow-up, October 2020).
 INTERVENTIONS Enteral L rhamnosus GG (1 × 10
10 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in
the ICU

40. SUBGROUP ANALYSES: VENTILATOR-
ASSOCIATED PNEUMONIA

41. RESULTS
 Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years),
2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years;
1063 women [40.1%.] with a mean Acute Physiology and Chronic Health
Evaluation II score of 22.0 (SD, 7.8) and received the study product for a
median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318
patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%;
hazard ratio [HR], 1.03 (95%CI, 0.87-1.22; P = .73, absolute difference,
0.6%, 95%CI, –2.5%to 3.7%).
 None of the 20 prespecified secondary outcomes, including other ICU-
acquired infections, diarrhea, antimicrobial use, mortality, or length of stay
showed a significant difference.
 CONCLUSIONS
 Among critically ill patients requiring mechanical ventilation,
administration of the probiotic L rhamnosus GG compared with
placebo, resulted in no significant difference in the development
of ventilator-associated pneumonia. These findings do not
support the use of L rhamnosus GG in critically ill patients.

42. CURRENT CHALLENGES FOR PROBIOTICS IN
THE ICU.
Schuurman, A.R.; Kullberg, R.F.J.; Wiersinga, W.J. Probiotics in the Intensive Care Unit. Antibiotics 2022, 11, 217.

43. © 2021, International Scientific Association for Probiotics and Prebiotics

44. © 2021, International Scientific Association for Probiotics and Prebiotics

45. © 2021, International Scientific Association for Probiotics and Prebiotics