Symposium on Advances in Pediatric Intensive Care

Probiotic Use in the Critically lLL

Sunit C. Singhi and A. Baranwal
Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research,
Chandigarh, India

ABSTRACT
Probiotics are live microbes which when administered in adequate amounts confer a health benefit to the host (FAO/WHO
joint group). Their potential role in bio-ecological modification of pathological internal milieu of the critically ill is under
evaluation. Probiotics are available as single microbial strain (e.g., Bacillus clausii, Lactobacillus) or as a mix of multiple strains
of Lactobacillus (acidophilus, sporogenes, lactis, reuteri RC-14, GG, and L. plantarum 299v), Bifidobacterium (bifidum, longum,
infantis), Streptococcus (thermophillus, lactis, fecalis), Saccharomyces boulardii etc. Lactobacilli and Bifidobacteria are grampositive, anaerobic, lactic acid bacteria. These are normal inhabitant of human gut and colonize the colon better than others.
Critical illness and its treatment create hostile environment in the gut and alters the micro flora favoring growth of pathogens.
Therapy with probiotics is an effort to reduce or eliminate potential pathogens and toxins, to release nutrients, antioxidants,
growth factors and coagulation factors, to stimulate gut motility and to modulate innate and adaptive immune defense
mechanisms via the normalization of altered gut flora. Scientific evidence shows that use of probiotics is effective in prevention
and therapy of antibiotic associated diarrhea. However, available probiotics strains in currently used doses do not provide much
needed early benefits, and need long-term administration to have clinically beneficial effects (viz, a reduction in rate of infection,
severe sepsis, ICU stay, ventilation days and mortality) in critically ill surgical and trauma patients. Possibly, available strains
do not adhere to intestinal mucosa early, or may require higher dose than what is used. Gap exists in our knowledge regarding
mechanisms of action of different probiotics, most effective strains- single or multiple, cost effectiveness, risk-benefit potential,
optimum dose, frequency and duration of treatment etc. More information is needed on safety profile of probiotics in immunocompromised state of the critically ill in view of rare reports of fungemia and sepsis and a trend toward possible increase in
nosocomial infection. At present, despite theoretical potential benefits, available evidence is not conclusive to recommend
probiotics for routine use in the critically ill. [Indian J Pediatr 2008; 75 (6) : 621-627] E-mail: sunit.singhi@ gmail.com
Key words: Probiotics; Critically ill; Intensive Care unit; Children

Live microbes and fermented food-products are in use for

their health-promoting effects since pre-Vedic and Vedic
period. Moreover, Ayurveda recommended Dahi (curd)
for its therapeutic effect in diarrheal patients much before
the microbial existence was recognized. In modern times,
Metchnikoff identified the possible health benefits of lactic
acid bacteria (LAB) viz., Lactobacillus bulgaricus and
Streptococcus thermophillus at the turn of the last century.
Subsequently, the term probiotics was coined by Lilley
and Stillwell in 1965.1 Recently, it has been defined by a
Joint Working Group of FAO/WHO as live microbes
which when administered in adequate amounts confer a
health benefit to the host.2 Development of target-specific

Correspondence and Reprint requests : Prof. Sunit C. Singhi, Head,

Department of Pediatrics, Advanced Pediatrics Center, PGIMER,
Chandigarh, India-160012. Ph.: +91-172-2746699, 2755301, Fax: +91172-2747099
[Received February 29, 2008; Accepted February 29, 2008]

Indian Journal of Pediatrics, Volume 75June, 2008

probiotics is the focus of current research. Their potential

role in bio-ecological modification of pathological internal
milieu of the critically ill is under evaluation. This review
will examine current status of probiotics in care of the
critically ill as per available evidence, and will try to
identify direction for future research.
Gut Microflora and their Significance
Gut represents a complex ecosystem with a delicate
balance between the microflora and the host. Human gut
contains about 400 different species of microbes as
commensals; total estimated number being >10 times the
number of eukaryotic cells in the human body. They
constitute about 60% of fecal solids. 3 Human gut
microflora is principally comprised of obligate anaerobes
(about 95%) and facultative anaerobes (1-10%). Obligate
anaerobes include Bifidobacterium, Clostridium,
Eubacterium, Fusobacterium, Peptococcus, Peptostreptococcus
and Bacteriodes; and facultative anaerobes are
Lactobacillus, E. coli, Klebsiella, Streptococcus, Staphylococcus
and Bacillus. Very small amounts of Pseudomonas
621

S.C. Singhi and A. Baranwal

aeruginosa is also there. Each human being has his own
unique microbial collection especially of lactic acid
bacterial (LAB) strains, e.g., Bifidobacterium and
Lactobacillus. Bifidobacteria are the predominant microbes
representing up to 80% of the cultivable fecal bacteria in
infants and 25% in adults. Peristaltic movement, secretion
of gastric acid and bile salts check the overgrowth of
microflora and helps to maintain a concentration gradient
away from proximal gut (Fig. 1). Majority of these
microbes have health promoting effects; a few species are,
however, potentially pathogenic. The good microbes
outnumber potentially pathogenic bacteria and live in
symbiosis with host, benefiting the later (Fig. 2). The
optimal composition and function of the flora depends on
the supply of food destined for colonic bacteria
(fermentable fibers, complex proteins, GI secretions) and
fluctuates with antibiotic usage, diarrheal diseases and
critical illness.

and small bowel,5 help in development of a competent

gut-associated immune system6 and maintain a chronic
and immunologically balanced inflammatory response.
The gut microflora provide physical barrier against
invading pathogens, the so called colonization
resistance. The mechanisms for barrier effects include (i)
competition for epithelial cell adhesion sites preventing
epithelial invasion (ii) competition for available nutrients
affecting survival of potential pathogens and (iii)
production of anti-bacterial substances (e.g., bacteriocins,
lactic acid) making the get environment unsuitable for
growth of potential pathogens. Microflora has nutritive
functions as well. It produces several enzymes and
biochemical pathways for fermentation of non-digestible
dietary residue and endogenously secreted mucus7 and
helps in recovering lost energy in form of short chain fatty
acids. They also play a part in synthesis of vitamins,8 and
in absorption of calcium, magnesium and iron.9
Critical illness, Gut, Sepsis and rationale of Probiotic
use

Fig. 1. Normal composition of gut microflora.

10

Pathogenic Effects

Health -promoting Effects

P. aeruginosa

Number/gm
of feces

Proteus

Exogenous &
harmful Endogenous
bacteria

Staphylococci

Pathogenic

Gastric acid
Bile salts

10

Clostridium

10

Immune
Stimulation

Enterococci

Gut motility
E. coli
10

Lactobacilli

Streptococci

Intestinal
putrefaction

Digestion of
Nutrients &
Minerals

Eubacteria

Bifidobacteria
Bacteroides
10

11

Synthesis of
Vitamins

Fig. 2. Delicate balance in gut microflora favors the host.

The gut microflora is important for development of

normal intestinal morphology. Studies on animals raised
in germ-free environment have hypoplastic intestinal
epithelium, reduced gut immunity, and impaired
peristalsis all of which improved when normal gut flora
were introduced. 4 The gut microflora stimulate the
epithelial cell proliferation and differentiation in the large
622

Critical illness and their care in the modern ICUs create

hostile environment in the gut and alters the microflora
tilting the balance to favor pathogens. The hostile
environment is contributed by various physical and
chemical changes namely broad-spectrum antibiotics,
changes in nutrient availability, gut motility, pH, oxygen
concentration, redox state, osmolality and release of high
levels of stress hormones including catecholamines.10 In
fact, stress-release of nor-epinephrine from sympathetic
nerve endings, which are in highest concentration in gut
epithelium, reduces the good microbes.11 In experimental
models of acute pancreatitis disappearance of beneficial
LABs was seen after 6 to 12 hours.12 Human studies have
also shown similar loss of LABs in the critically ill after a
short ICU-stay.13 Reduction in LABs breaks down the
colonization resistance and leads to overcrowding of
potential pathogens. With capability to sense their own
overcrowding, the potential pathogens adapt themselves
to express virulence genes for self-protection and invasion
after having achieved a critical biomass in face of
otherwise limited resources during such opportunism or
adversity.14 Overgrowth of various potentially pathogenic
commensals like Salmonella, E. coli, Yersinia, P. aeruginosa
have been shown to cause one or more of cytokine
release, cell apoptosis, activation of neutrophils and
disruption in epithelial tight junction permeability.11 Gut,
with loss of colonization resistance, is unable to prevent
the translocation of pathogens and toxins across the gut
wall into the blood stream. Overgrowth of pathogens and
microbial translocation have been shown to occur within
6-12 hours of inducing acute pancreatitis in experimental
studies.12,15,16 Not surprisingly, gut has been identified as
origin and promoter of nosocomial sepsis and multiorgan failure in the critically ill,17 which is the major
determinant of ICU outcome.
Indian Journal of Pediatrics, Volume 75June, 2008

Probiotic Use in the Critically Ill

Reversing the pathological microfloral tilt with
exogenous supply of new and effective flora (probiotics)
with/without food for the flora (prebiotics) seems an
attractive and non-invasive attempt to restore natural
flora and thus the colonization resistance. It is likely to
prevent microbial translocation and subsequent systemic
inflammatory response. Probiotics (especially LABs)
represent a therapeutic effort to reduce or eliminate
potential pathogens and toxins, to release nutrients, antioxidants, growth factors, coagulation factors, to stimulate
gut motility 18 and to modulate innate and adaptive
immune defense mechanisms19 via the normalization of
altered gut flora.
The appeal of probiotics in critical care setting is
threefold. First, the existing safety record renders them
attractive over many of the more aggressive therapeutic
options. Second, they represent a simple, non-invasive
attempt to recreate natural flora rather than a disruption
of the nature. Third, the proposed use is for prevention of
disease in a select group of patients which is associated
with high mortality.

2. Flora-SB

3. Lactisyn

4. Eugi

5. Prowell

6. Biogut

Currently Available Probiotics and their Mechanism of

action
The effectiveness of probiotics is related to their ability to
survive in the acidic and alkaline environment of stomach
and duodenum respectively, as well as their ability to
adhere to the colonic mucosa and to colonize the colon.
Some probiotics, e.g., Lactobacillus GG and L. plantarum
299v are better able to colonize the colon than others.
Saccharomyces boulardii are non-LA yeast and secret a
protease causing proteolysis of Toxin A and Toxin B of Cl.
difficile responsible for antibiotic associated diarrhea
(AAD). Bacillus clausii are gram positive spore-forming
strictly aerobic non-LAB and constitute less than 1% of gut
microflora. B. clausii stimulate CD4 proliferation and
TABLE 1. Commercially Available Probiotic Preparations in
Indian Market.
No. Products
Single strain probiotics
1. Cynobac Tender/
Baclac/Lactra/
Rexflora kid tab/
Oraflora
2. Cynobac/
Rexflora Cap
3. Econorm/Biogit/
Stibs
4. Laviest
5. Enterogermina

7. Bifilin

8. Binifit

9. Ecoflora

10. Flora-SB

Composition
Lactobacillus sporogenes (60 million
spores/Tab)

Lactobacillus sporogenes (180 million

spores/Tab or Cap)
Saccharomyces boulardii (250 mg/ Sachet)
Saccharomyces cerevisiae P (10 million
cells/Cap)
Bacillus clausii (200 million spores/5 ml)

Multi-strain probiotics
1. Bifilac
Lactobacillus sporogenes (50 million
spores)
Streptococcus fecalis (30 million)
Clostridium butyricum (2 million)
Bacillus mesentricus (1 million)

Indian Journal of Pediatrics, Volume 75June, 2008

11. Diacowin

Lactobacillus acidophilus (75 mg)

Lactobacillus rhamnosus (75 mg)
Bifidobacterium longum (75 mg)
Bifidobacterium bifidum (50 mg)
Saccharomyces boulardii (50 mg)
Lactobacillus lactis (490 million)
Lactobacillus acidophilus (490 million
spores)
Streptococcus thermophillus (10 million)
Streptococcus lactis (10 million)
Lactobacillus acidophilus (240 million)
Lactobacillus rhamnosus (240 million)
Bifidobacterium longum (240 million)
Bifidobacterium bifidum (240 million)
Saccharomyces boulardii (50 million)
Streptococcus thermophillus (240 million)
Fructo-oligosaccharides (300 mg)
Lactobacillus acidophilus (5000 CFU)
Bifidobacterium bifidum (5000 CFU)
Bifidobacterium longum (5000 CFU)
Bifidobacterium infantis (5000 CFU)
Fructo-oligosaccharides
Lactobacillus acidophilus (300 million)
Lactobacillus rhamnosus (300 million)
Lactobacillus paracasei (300 million)
Lactobacillus sporogenes (1200 million)
Bifidobacterium longum (300 million)
Saccharomyces boulardii (600 million)
Inulin (200 mg)
Fructo-oligosaccharides (200 mg)
Lactobacillus acidophilus (500 million)
Lactobacillus rhamnosus (500 million)
Bifidobacterium bifidum (500 million)
Bifidobacterium longum (500 million)
Streptococcus thermophillus (250 million)
Saccharomyces boulardii (250 million)
Fungal Amylase (200 mg)
Fructo-oligosaccharides (100 mg)
Streptococcus fecalis (30 million)
Clostridium butyricum (2 million)
Bacillus mesentricus JPC (1 million)
Lactobacillus sporogenes (50 million)
Lactobacillus rhamnosus GR-1 (1000
million CFU)
Lactobacillus reuteri RC-14
Lactobacillus acidophilus (40 mg)
Lactobacillus rhamnosus (40 mg)
Bifidobacterium bifidum (25 mg)
Bifidobacterium longum (40 mg)
Saccharomyces boulardii (25 mg)
Fructo-oligosaccharides (100 mg)
Saccharomyces boulardii (141.25 mg)
Lactic Acid Bacilli (50 million)

lymphocytic activity in Peyers patches. It also lead to

increase in IgA-positive lymphocytes and HLA-DR
positive T lymphocytes. Bifidobacteria are gram-positive
anaerobic LAB, colonize the colon within days of birth
and its population remains stable until advanced age.
Lactobacilli are gram-positive, facultative anaerobic LAB
and are normal inhabitant of human gut. L. plantarum
299v adheres to intestinal mucosa to re-inforce its barrier
function, thus prevents attachment of pathogens to the
intestinal wall. Lactobacilllus GG was found to eradicate Cl.
difficile in patients with relapsing colitis. L. plantarum ST31
623

S.C. Singhi and A. Baranwal

produce bacteriocins to limit the growth of potential
pathogens. L. casei increases level of circulating IgA. L.
acidophilus and B. bifidum appear to enhance the
phagocyte activity of circulating granulocytes. Many LAB
strains have anti-oxidative ability. Probiotics are also
shown to decrease intestinal permeability in the critically
ill.19 Multi-strain probiotics seems to be better than singlestrain ones, as individual probiotics have different
functions and show synergistic effects when administered
together. 18,20 Various single-strain and multi-strain
probiotics are commercially available for clinical use,
majority being LABs. Some of the preparations available
in Indian market are listed in table 1.
Probiotics in Critical illness: Available Evidence
Scientific evidence for prophylactic and therapeutic use of
probiotics in various disorders e.g., infectious diarrhea is
accumulating. With foregoing discussion, there seem to
be enough conceptual premises for probiotics to be
helpful in the critically ill as well, however the same
requires to be corroborated by clinical evidence. To be
clinically useful, following issues need to the resoled.
Whether probiotic adhere to the gut of critically ill ?
For possible positive effect, the administered probiotic
need to remain viable during gastric and intestinal transit.
Moreover, >10 7 colony forming units/ml of viable
microbes should reach the intestine21 and microbes should
adhere tightly on to the unfavorable gut mucosa of the
critically ill. In a small study population of critically ill
children, L. casei shirota has not led to colonization.22
However, in a randomized controlled trial (RCT) (n=69),
B. lactis Bb12 was shown to significantly increase the
Bifidobacterial count in the feces of preterm neonates after
continuous use of 7-21 days.23 In a small study (n=8) on
critically ill adults receiving broad spectrum antibiotics, L.
plantarum 299v was shown to colonize the rectal mucosa
only in 3 patients, that too by 7 days.24 Though microbes
were able to survive and adhere to the rectal mucosa, the
effect was seen too late and in lesser number of patients.
A probiotic with early and better adherence is needed for
their positive effect on the critically ill.
Whether probiotics prevent and restore the alteration in
microfloral composition?
Having colonized the gut mucosa, probiotic need to
prevent the growth of potential pathogens. In a RCT
(n=69), B. lactis Bb12 was shown to reduce the viable
counts of Enterobacteriaceae and Clostridium spp. in the
feces of preterm infants after continuous use of 7-21
days.23 In another RCT (n=80) on very low birth weight
preterm babies, L. casei rhamnosus was shown to reduce
candidal colonization of gut in significant number of
patients (48.8% vs 23.1%, P=0.01), however after 6 weeks
of continuous administration. Intensity of colonization
was also lesser in probiotic treated group.25 Similarly, in a
RCT (n=90) a multi-strain synbiotic has led to lower
624

incidence (43% vs 75%, p= 0.05) of potential pathogens in

nasogastric aspirates of the critically ill, after 7 days of
continuous use. However, this favorable alteration in
upper gut didnot get translated in measurable clinical
benefits viz., septic complications and mortality.26
Whether probiotics reduce Translocation, Nosocomial
Sepsis, and thus Mortality?
In an experimental model of endotoxemia, 8 days pretreatment with L. plantarum 299v had significantly
reduced bacterial translocation in mesenteric lymph
nodes and liver.27 However, to be clinically effective in
critical care setting, the probiotic should be effective when
used after the onset of SIRS and/or endotoxemia. In a
large (n=585) placebo-controlled RCT, prolong
administration of Lactobacillus GG was not able to reduce
incidence of urinary tract infection, necrotizing
enterocolitis and bacterial sepsis in preterm newborns
(<33 weeks or < 1.5 kg birth weight). 28 By day 7 of
probiotic use (n=28), significantly increased serum IgA,
IgG levels and decreased intestinal permeability was
demonstrated in most critically-ill patients, however there
was no impact on the MODS scores. 19 Similarly, L.
plantarum 299v (n=103) had shown late attenuating effect
(i.e., after 15 days) on systemic inflammatory response on
critically ill patients as measured by serum IL-6 levels, but
again it didnot reduce sepsis morbidity and mortality.29 A
recently published RCT (n=61) revealed no benefit of
probiotic (L. rhamnosus GG) use in prevention of
nosocomial infection in PICU.30 A systematic review (8
RCTs; n=999) revealed no beneficial effect of probiotics/
synbiotics on critically ill adults in term of clinical
outcomes, viz. length of ICU stay, incidence of nosocomial
infection, pneumonia and hospital mortality.31
In contrast, in a RCT (n=65) on critically ill,
mechanically ventilated multiple trauma patients, 15 days
of multi-strain probiotic therapy (with prebiotics) led to
significant reduction in rate of infection, SIRS, severe
sepsis, ICU stay, ventilation days and mortality.32 Another
randomized but small (n=20) trial in brain-injured
patients, probiotic (with glutamine) given for 5 to 14 days,
was shown to significantly reduce the incidence of
infection (50% vs 100%, p=0.03), ICU stay (10 vs 22 days,
p<0.01) and ventilation days (7 vs 14 days, p=0.04). It also
significantly reduced the median number of infection per
patient.33 Similarly, a synbiotic preparation (n=145) was
shown to reduce the incidence and severity of necrotizing
enterocolitis in low birth weight neonates (<1500 gm).34
With foregoing discussion, it is obvious that probiotics
used in currently available strains and currently
recommended doses, are not able to provide much
needed early benefits, and rather need long term
administration to have its measurable effects and so may
be beneficial in critically ill surgical and trauma patients.
Possibly, available strains do not adhere to intestinal
mucosa early, or may require higher dose than what is
Indian Journal of Pediatrics, Volume 75June, 2008

Probiotic Use in the Critically Ill

being studied. In developing economies, majority of
critically ill children have various infectious diseases as
indication for PICU admission, and usually stay for
relatively shorter period. For example, only 28% of
surviving patients with disseminated staphylococcal
disease stayed in PICU for >7 days in our experience.35
Thus, despite theoretical potential benefits, available
evidence is not conclusive to recommend it for routine use
in the critically ill.36,37
Probiotic in Antibiotic Associated Diarrhea (AAD):
Available Evidence
With frequent use of broad spectrum antibiotics in critical
care setting, AAD is frequently observed among critically
ill children. Decrease in population of microbes having
beneficial metabolic functions and overgrowth of
pathogens contribute to the osmotic and invasive diarrhea
respectively.38 A meta-analysis of 9 placebo-controlled
RCTs (conducted during 1966-2000, including 2 pediatric
RCTs) revealed probiotics to be effective in prevention of
AAD; S. boulardii and lactobacilli having the best
potential.39 Another meta-analysis of 6 pediatric placebocontrolled RCTs (till 2005, n=766) have shown reduced
incidence of AAD in probiotic treated patients. Further
analysis revealed that if 7 patients are going to develop
diarrhea out of all patients receiving antibiotics, one can
be prevented if all of them received probiotics along with
antibiotics.40 Obviously, with the available preparations
cost-benefit ratio of AAD-prevention does not seem to be
clinically favorable.
A meta-analysis of 7 RCTs (n=881) revealed beneficial
therapeutic role of probiotics in AAD.41 To address the
issue in children, meta-analysis of 6 RCTs (n=707) were
performed. It revealed beneficial effect; however the same
could not withstand intention-to-treat analysis.42 Thus it
was opined to have large well-designed trials to look into
the cost of and need for routine use of probiotics in
AAD.39 While all these studies had tried to address the
issue of probiotic use for AAD in non-critical care setting,
AAD in the critically-ill has not received similar
attention.43
Safety Issues
Though probiotics do not seem to pose a significant risk of
infection,44 thorough understanding of risks and benefits
is imperative while beneficial effects are being evaluated.
In 28 critically ill children, use of L. casei shirota was safe
and has led to neither colonization nor bacteremia.22 Use
of probiotics was found to be safe in surgical 45 and
critically ill patients.24 However, there are rare reports of
fungemia and sepsis in immunocompromised patients46 as
well as in the critically ill 47,48 with use of S. boulardii.
Recently, use of L. rhamnosus GG in PICU patients was
shown have a statistically nonsignificant trend toward an
increase in nosocomial infection.30 Other theoretical safety
concerns are genetic transfer of antibiotic resistance,
Indian Journal of Pediatrics, Volume 75June, 2008

deleterious metabolic activities and excessive immune

stimulation in susceptible individuals,2 and need to be
addressed.
Well-designed, large and detail studies are required to
address the risk-benefit potential of therapeutic usage.
The risk and morbidity of probiotic-induced sepsis need
to be weighed vis--vis its preventive potential against
sepsis in the critically ill. The European Society of
Pediatric Gastroenterology, Hepatitis and Nutrition
(ESPGHN) committee on nutrition recently summarized
its approach to probiotics as follows Probiotics so far
used in clinical trials can be generally considered as safe.
However, surveillance for possible side effects, such as
infection in high-risk group (read, critically-ill group), is
lacking and is needed.49
Future Research Direction for Critical Care Use
Probiotics represent promising advance in the field of
prophylaxis and therapy, however much more need to be
done as far as its use in the critically ill is concerned.
Following are the areas for further research:
It is important to achieve tight adherence of probiotic
onto the intestinal mucosa, which may be difficult in
critical illness. Higher doses of existing strains or search
for different strains may be required.
Most of strains colonized the intestine, but did so after
one week of consumption. What we need is early and
effective mucosal adherence, preferably within 48
hours, to prevent multi-organ dysfunction in septic
pediatric patients.
Search for clinically beneficial probiotic strains which
have ability to eliminate unwanted antibiotic-resistant
gut pathogens, to prevent sepsis and to reduce SIRS.
More research is needed for better understanding of
pharmacokinetics, mechanism of action and selection
of specific probiotic (single-strain or multi-strain) for
specific critical care conditions.
It is known that probiotic preparations are highly
heterogeneous with difference in composition,
biological activity and clinically beneficial dose.
Research is needed in areas like appropriate dose,
administrative regimens and probiotic interactions.
Properties of different probiotic species vary and are
strain-specific. Therefore, the effects of one probiotic
strain cannot be generalized to others without
confirmation in separate studies.
Though probiotics are proven to be safe in healthy
children, more information is needed on their safety
profile in immunocompromised state of the critically
ill.
Significance of additional use of prebiotics need to be
defined.
625

S.C. Singhi and A. Baranwal

Available evidence suggest potential role of probiotic
in care of the critically ill. Recent ventures in metabolic
engineering and heterologous protein expression have
enhanced the enzymatic and immunomodulatory effects
of probiotics and with time, may allow more active
intervention for its use in the patients under
consideration.
CONCLUSION
With increasing knowledge, eco-immunonutrition with
probiotics and synbiotics seem to be logical tools in care of
the critically ill, however major gap exists in our
knowledge regarding mechanisms of action of different
probiotics, most effective strains single or multiple, cost
effectiveness, risk-benefit potential, optimum dose,
frequency and duration of treatment. There is long way to
go to have strain(s), which is clinically beneficial in the
critically ill. Optimally designed, well-powered,
randomized, large clinical trials with reproducible results
are required to define their preventive and therapeutic
role before routine use can be recommended.
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