Allergic Disease - Probiotics and Prebiotics

Allergic Disease - Probiotics and Prebiotics 
Category: Health Condition/ Disease
Practice Questions
Q1: What is the safety and efficacy of probiotic supplementation for the treatment of eczema
among infants, children and adults?
Subcategory: Intervention
Updated: 2018-12-31
Key Practice Point #1

Recommendation
Currently available probiotic strains (mostly Lactobacillus species but some Bifidobacteria species)
probably do not have much effect on parent- or patient-rated eczema symptoms or quality of life. They
may have a small, but clinically uncertain, benefit on investigator-rated eczema severity score after
supplementation, and eczema severity and number of flares over the month or two after supplementation
ends. However, in the studies examined, the probiotic supplements were well tolerated with no more
adverse effects reported with probiotics than with control/placebo. Only a few studies were low risk of bias
and many were of short duration; more research of longer duration and higher quality is needed to confirm
whether probiotics can or cannot help treat eczema.
Evidence Summary
A Cochrane meta-analysis of RCTs on the safety and efficacy of probiotics for the treatment of eczema
found that one to four months of supplementation with probiotics (mostly Lactobacillus species but some
Bifidobacteria species) did not improve participant- or parent-rated symptoms at the end of the
supplementation period. However, meta-analysis of the few studies that had follow up did find
a statistically significant improvement over the two to eight weeks after supplementation ended; although it
was small benefit and of uncertain clinical relevance. Additionally, meta-analysis detected a significant
improvement in investigator-rated eczema severity scores (Severity Scoring of Atopic Dermatitis -
SCORAD Scale) with probiotic supplementation. Analysis of the few follow-up studies also found
a difference in favour of probiotics for changes in global eczema severity and number of flares over the two
to eight weeks after supplementation ended. Meta-analysis found no benefit of probiotics on scores of
quality of life at the end of supplementation or at/up to eight weeks follow up (post supplementation)
period.
There were no difference in adverse effects (gastrointestinal symptoms) between probiotics and
control/placebo.
Grade of Evidence: B
Remarks
While it has been shown that the nature or composition of the microbiome is different in those with
eczema versus those without (such as lower bifidobacteria presence with eczema and progressively lower
Allergic Disease - Probiotics and Prebiotics

© 2021 Dietitians of Canada. All rights reserved. PAGE 1
bifidobacterial with progressively more severe eczema) it is not yet clear if supplementation can alter this
and then subsequently impact other body systems such as the skin and/or the immune system and then
impact eczema presence or severity. Nor is it known how long treatment would need to be in order to elicit
change, if possible.
Evidence
a. Authors of a 2018 Cochrane review on the effect of probiotics for treating eczema identified 39
RCTs (n=2599) that met inclusion criteria (1). While there was no age restriction on the
population for inclusion criteria, most studies were conducted on children: in 14 RCTs, the study
participants were <18 months of age, in 33 RCTs the participants were <18 years of age and six
RCTs were on adults. In total, the age of the participants ranged from 0-55 years of age who had
doctor-diagnosed mild to severe eczema. Most of the studies were conducted in Europe (22
RCTs) with the remaining in Asia (eight RCTs) and Australasia (two RCTs). Supplementation
lasted from four to 16 weeks with anywhere from no follow up or up to eight weeks of follow up
after supplementation was discontinued. The probiotics used were mostly from the Lactobacillus
species and some also from the Bifidobacteria species and dose was highly variable across the
different studies. Meta-analysis of 13 trials (n=754) found no significant benefit of probiotic
supplementation on participant- or parent-rated symptoms at the end of the supplementation
period (MD=-0.44 (on a 0-20 scale), 95%CI, -1.22 to 0.33, with statistical heterogeneity,
moderate quality evidence). However, meta-analysis of the three studies (n=195) that had data
on eczema symptoms two to eight weeks following end of supplementation period did find
statistically significant improvement with probiotics on patient- parent-rated symptom score
[SCORAD C] (MD=-1.81, 95%CI, -3.13 to -0.49 with no heterogeneity). Meta-analysis of six
studies (n=552) found no benefit of probiotics on scores of quality of life (SMD=0.03, 95%CI, -
0.36 to 0.42, with statistical heterogeneity, low quality evidence) at the end of supplementation
and meta-analysis of two RCTs (n=261) also found no significant benefit at up to eight weeks
follow up (post-supplementation period). Meta-analysis of 24 trials (n=1596) found a small but
statistically significant improvement in investigator-rated eczema severity scores (the 0-103
SCORAD – Severity Scoring of Atopic Dermatitis with probiotic supplementation (MD=-3.91 on
the SCORAD, 95%CI, -5.86 to -1.96, high statistical heterogeneity). Cochrane review authors
noted that other investigators have suggested that the minimum clinically significant difference on
the SCORAD is estimated to be either 4.1 or 8.7 points. Hence, the 3.91 point difference, while
statistically significantly different, may not be clinically significant. Sensitivity analysis of the
data on changes in scores (difference in SCORAD between pre- to post- treatment for each
individual) found improvement with probiotics that was statistically and possibly clinically
significant (MD=-4.46, 95%CI, -6.49 to -2.43, 14 RCTs, n=1035, with some heterogeneity).
Follow-up analysis of seven RCTs (n=509) also found a difference in favour of probiotics for
changes in global eczema severity and number of flares over the two to eight weeks after
supplementation ended (MD=-7.72, 95%CI, -11.85 to -3.59, high heterogeneity thought to be due
to the differences in the duration of the follow-up period.) Subgroup and stratified analysis
indicated no difference as a function of age, severity of eczema, single versus multi-strain or
whether or not prebiotics were used in addition to the probiotics. Adverse effects that were
reported in the trials consisted primarily of gastrointestinal complaints such as diarrhea,
constipation, abdominal colic, or vomiting. However, meta-analysis of seven trials (n=402) found

no difference between probiotic and control groups for these adverse effects (RR=1.54, 95%CI,
0.90 to 2.63, low quality evidence, no heterogeneity) indicating that probiotics did not increase
the risk of adverse effects in this population. The review authors’ overall conclusion was that
currently available probiotic strains probably do not have much effect on patient-rated eczema
symptoms or quality of life and may have a small, clinically uncertain, benefit on investigator-
rated eczema severity score. They acknowledged that the low efficacy observed in their meta-
analyses could be due, at least in part, to the short duration of the trials failing to allow enough
time for modulation of the microbiome composition or function. They noted that not enough
studies had adequate long-term follow up and so clear conclusions on longer term evaluation is
not yet clear. They recommended that future studies report long-term follow up, such as six
months after active supplementation has ended to observe changes in eczema (1). A longer
evaluation period (supplementation and/or follow-up time post supplementation) may be needed
to adequately modify the microbiome to the point such modification can then lead to changes in
other body tissues such as the skin and immune responses. Nine of the RCTs were low risk of
bias and so there is room for improvement in study design and execution in addition to duration
of observation.
Comments
While the terms “eczema” and “atopic dermatitis” have often been used interchangeably, just under half of
children with eczema do not test positive on skin prick test for atopy (1). With atopy, one produces IgE
antibodies in response to the allergen. The latest World Allergy Organization nomenclature proposes that
the term “eczema” replace the term “atopic eczema/dermatitis syndrome”. Atopy can only be used if IgE
sensitivity is confirmed by blood IgE antibodies or positive skin prick test. Consequently, eczema can be
classified as atopic or non-atopic. The Cochrane review that informs the above Key Practice Point used
the more general or broad term of eczema, thereby including studies on eczema with or without IgE
sensitization confirmation.
Rationale
The rationale behind supplementation with probiotics is that the intestinal microflora/microbiota
composition has been found to be different in those with eczema versus those without eczema (1). In
particular, research found significantly lower proportion of Bifidobacterium species in those with eczema
versus those without and lower proportion of Bifidobacterium species to be associated with greater
severity of eczema. However, most (approximately 2/3) of the studies on probiotics for eczema used
Lactobacillus species while fewer (approximately 1/3) used Bifidobacterium species.
References
1. Makrgeorgou A, Leonardi-Bee J, Bath-Hextall FJ, Murrell DF, Tang ML, Roberts A, et al.
Probiotics for treating eczema. Cochrane Database Syst Rev. 2018 Nov 21;11:CD006135. doi:
10.1002/14651858.CD006135.pub3. Abstract available from:
https://www.ncbi.nlm.nih.gov/pubmed/30480774
Q2: Are there any safety concerns with the use of probiotics?

Subcategory: Monitoring/Evaluation
Updated: 2019-06-26
Key Practice Point #1

Recommendation
Probiotic products are generally safe for those in good general health. However, caution should be
exercised when considering using probiotics among high risk groups such as critically ill patients and
hospitalized and postoperative patients of all ages due to the risk of serious infection (bacteremia,
fungemia, sepsis and endocarditis, in particular) among these vulnerable groups.
Caution may also need to be taken if one has or is living with someone who has an indwelling venous
catheter as there have been some cases of infection linked to environmental exposure (probiotic powder
airborne contaminating catheter tips and then entering the blood stream this way).
Cautions/contraindications/risk information found on product label should be followed. Product labels

generally caution against product use by those with an immune-compromising condition or those on long-
term corticosteroid treatment.
Allergy
Those with known food allergies, particularly to cow’s milk, egg and soy proteins:
should avoid probiotics that indicate on the label that they could contain allergens
may even wish to avoid probiotics where the label explicitly indicates or suggests it is free of
particular allergens as there have been some rare cases of anaphylactic reactions attributed to
probiotics that contained allergens that the label had not declared. If not avoiding, then it would
be prudent to at least consider the risk benefit ratio of using probiotics on the individual basis
among those with allergies.
Evidence Summary
A systematic review and meta-analysis of hundreds of RCTs and clinical controlled trials on tens of
thousands of children and adults being treated with probiotics found no difference in the rate of side-effects
or adverse events between probiotic and control conditions. However, a few dozen case reports have found
various probiotics to be strongly linked (and often culture confirmed) to infection such as sepsis,
endocarditis, bacteremia (Lactobacillus, Bifidobacterium) and fungemia (Saccharomyces boulardii) among
high risk and vulnerable population groups such as those who are critically ill, postoperative, hospitalized
or who have venous indwelling catheters. Catheters were attributed as a route of transmission of infection
even among individuals who were not administered probiotics themselves but were in a hospital bed beside
individuals who were. The powder can become airborne and contaminate equipment, surfaces, hands etc.
Case reports from Europe described a few cases of young children with cow’s milk allergy or both cow’s
milk and egg allergy developing an anaphylactic reaction within moments of ingesting probiotic
supplement. Additionally, experimental skin prick test trials motivated by these cases also found children
with allergy to test positive to probiotic supplements that did not indicate on the label they contained
allergens (cow’s milk proteins, hydyrolyzed soy proteins, egg protein). The culture medium which grows

the probiotic can be a source of protein allergen in the resulting product.
Grade of Evidence: C
Remarks
Many probiotic product labels often note under caution or risk information that they should not be used by
those with an immune-compromised condition or those on long-term corticosteroid treatment. Product
labels also often encourage consulting a health care practitioner prior to use if pregnant, breastfeeding,
taking other medications or supplements, have a health condition and to discontinue use if digestive upset
occurs.
Evidence
a. Investigators described the case of an infant with cow’s milk allergy who incurred an anaphylactic
reaction with generalized urticaria and laryngeal edema fifteen minutes after ingestion of a
commercial probiotic supplement in France (1). Makers of the particular probiotic indicated that it
was grown on lactoserum proteins and medium containing casein. The investigators then
described a small study they ran on 10 children with cow’s milk allergy whereby they performed
skin prick tests with cow’s milk based infant formula and three different commercially available
probiotics. All 10 children tested positive for reaction to the cow’s milk formula, seven tested
positive for the same probiotic from the case study and 10 tested positive to a probiotic that was
grown in the presence of hydrolyzed soy proteins. Analysis of the probiotics detected beta-
lactoglobulin in the product from both the case study and the trial. The authors called for
manufacturers to ensure that their manufacturing procedures effectively eliminate residual food
allergens from the culture medium, to test for residual allergen in the final product and to declare
on product labels what type of culture medium was used.
b. In a 2012 report, investigators described the case of a six-year old girl in Spain who developed an
anaphylactic reaction in response to an acidophilus probiotic (2). The child was allergic to cow’s
milk and egg proteins. The child’s anaphylactic reaction occurred within moments of consuming
the probiotic solution. She recovered with immediate treatment for the anaphylactic reaction. The
probiotic product label claimed that it was free of milk proteins and it did not include any
information about egg protein content. However, analysis of the product detected the presence of
both cow’s milk and egg proteins. Investigators then sampled 11 probiotic products that were
commercially available in Spain to determine if they contained cow’s milk and egg protein.
Investigators also conducted skin prick tests of the probiotic solutions on 15 children aged five to
11 years (five of which had cow’s milk allergy, five of which had egg allergy and five had no
allergies). If the probiotic label indicated that it contained cow’s milk protein or egg protein than
those solutions were not tested on children with known allergy to the respective protein. Six
children with cow’s milk allergy had positive skin prick test to three of the probiotics and four
children with egg allergy had positive skin prick test to one of the probiotics. The children with no
allergies did not have a positive skin prick test to any of the probiotics. In three of the probiotic
supplements that contained no label warning that it could contain cow’s milk protein;
investigators quantified more than 2.5 mg/kg of cow’s milk protein in the product and one
supplement with more than 2.5 mg/kg of egg white protein in the product. Some of the probiotics

tested were pharmaceutical preparations and some were supplements, which fall under different
regulations in Spain. Investigators found that the pharmaceutical probiotics had more accurate
labeling information regarding potential allergens than the probiotic supplements. The authors
also noted that while cow’s milk is a common allergen and a common culture medium; other
protein sources that are also allergens could be used in culture too and so they questioned the
risk benefit ratio of probiotic use by those with known food allergies. The authors also called for
better screening tests of end products for residual food proteins.
c. In a systematic review of the safety of probiotics authors described the case reports in more
detail (3). The following are the conclusions for different probiotic species:
Lactobacillus species: Lactobacillus rhamnosus GG – five case reports among
neonates with medical conditions given Lactobacillus rhamnosus GG to treat antibiotic-
associated diarrhea or prevent small intestine bacterial overgrowth. All five infants
developed bacteremia and one infant who had cardiac stenosis developed endocarditis.
Bifidobacterium species: results of one case series and four RCTs among preterm
infants admitted to NICU linked prescription use of B. breve, B. lactis and B. langum
with functional ileus in two infants and one newborn with omphalocele developed
sepsis.
Combination Bifidobacterium and Lactobacillus: nine controlled trials conducted among
neonates and adults in the ICU with NEC, sepsis and constipation or post-surgery
indicated no adverse effects of combination treatment with Bifidobacterium and
Lactobacillus.
Saccharomyces boulardii: authors described 30 cases of preterm infant and adult post-
surgical patients who had underlying medical conditions who developed fungemia from
prescription use of S. boulardii given to prevent or treat diarrhea. However, one of the
infants who developed fungemia was not given S. boulardii but was in the cot located
next to the infant that was given S. boulardii and had developed fungemia. Yet another
four controlled clinical trials on S. boulardii among preterm infants, critically ill adults in
ICU and patients on enteral nutrition observed no adverse effects.
Synbiotics – combination of Bifidobacterium and Lactobacillus with prebiotics: in six
trials there were no adverse effects observed in pre-term infants or adults. In one
controlled trial with 296 patients with acute severe pancreatitis, treatment with probiotics
or control for 118 days found similar rates of infection as an adverse effect (30%
treatment, 28% control) but 16% mortality rate in treatment and 6% in control and nine
intestinal ischemia cases on treatment (8/9 died). Two other RCTs found no difference
between control and synbiotics for adverse effects.
The authors concluded from their review of the aforementioned evidence that the “most” at-
risk populations are critically ill patients (infants to adults), postoperative and hospitalized
patients and those who are immunocompromised. The authors recommended that before
prescribing probiotics the risk-benefit ratio be considered for each individual as it may be
different in healthy populations than in high risk groups. Additionally, because of the risk
of S. boulardii in patients with CVC or synthetic cardiac valve replacement the authors
recommended avoiding S. boulardii in these patients.
d. In a systematic review of the safety of probiotics among patients on nutrition support authors

evaluated case reports, RCTs and non-randomized studies (NRS) (4). The RCTs and NRS (53
trials, n=4131) did not find risk with probiotics and found mostly positive effects. However, 20
case reports on 32 patients did report adverse effects associated with two different types of
probiotics/yeasts: Lactobacillus rhamnosus GG (five cases of bacteremia, culture confirmed) and
Saccharomyces boulardii (27 cases of fungemia, culture confirmed). In these cases, the patients
(aged 1 month to 89 years) were all on enteral and/or parenteral nutrition, had central or
peripheral venous catheters and/or antibiotic therapy or immunotherapy and/or bacterial
translocation disorders such as colitis, sepsis, c. difficile and mucositis. Patients were treated
by stopping the probiotics and removal or change of the catheter. Death occurred in eight (25%)
of the cases. The concern is due in part to the fact that when on enteral or parenteral nutritional
support that bypassing gastric acidity could lead to increased probiotic survival and such
patients also have other vulnerabilities to infection. The review authors thought that the reason
the only two probiotics/yeasts linked to the infection were Lactobacillus rhamnosus GG and
Saccharomyces boulardii was not that these are more virulent strains, but that they are the more
commonly used products. The authors further stated that some infection may have occurred
because of environmental contamination (versus ingestion). Specifically, contamination of the
catheters due to probiotic powder in the air contaminating equipment or hands provides a route of
entry of probiotic into the circulation. Infection with Saccharomyces boulardii was detected in
patients who were not treated with Saccharomyces boulardii themselves, but instead were
located next to a patient who was treated with Saccharomyces boulardii. The review authors
recommended that caution be exercised when using probiotics in patients with risk factors such
as venous catheters or bacterial translocation disorders but that they need not be
contraindicated because there are potential benefits. Instead, they encouraged conducting a risk-
benefit analysis for each patient while also monitoring for adverse events.
e. The Agency for Healthcare Research and Quality commissioned an exploratory systematic
review which evaluated the published research evidence on the safety of probiotic therapy in
humans (5). The authors noted that, overall, there was very little research evidence focused on
probiotic safety and instead most of the research was focused on efficacy. Authors identified 622
studies (n=24615) for inclusion of which 235 made only general statements on the safety of
probiotics (i.e. products were well tolerated) while the other 387 studies provided more specific
information on side-effects. A total of 68% of studies used Lactobacillus in whole or part, 32%
used Bifidobacteria, 13% used Saccharomyces, 15% used Streptococcus, 5% used
Enterococcus and 3% used Bacillus. A total of 49% of studies were conducted in Europe, 11%
in US and 16% in Asia. Just over half of studies tested a single genus at once with others testing
products containing more than one genus. More than 90% of products were just probiotics (not
synbiotics). In 28% of studies subjects were also taking antibiotics. A total of 52 studies
intentionally excluded immunocompromised subjects, 73 excluded pregnant women and 36
excluded women who were lactating/breastfeeding. The study participants’ health status were on
a continuum ranging from “generally healthy” on one end to “critically ill/high risk” on the other
end with the median-indeterminate risk in the middle consisting of those with conditions such as
diarrhea, ulcerative colitis, bacterial vaginosis, etc. Most studies lasted one month or less with
only 5% being long term (1 year or more). Two thirds of studies administered the probiotic via the
oral route, with 10% of those being enteral tube route. Other routes of administration were
suppository, particularly vaginal suppository. Adverse events were directly assessed or reported

via means such as provider assessment, patient diaries, questionnaires, phone interviews and
lab tests. Reported side-effects in trials were typically gastrointestinal in nature such as bloating,
fullness, diarrhea, flatulence and nausea but this was not different between probiotic and control
groups. Meta-analysis of 121 studies reported no difference between conditions for number of
study participants with adverse events (RR=0.98, 95%CI, 0.93 to 1.04). Meta-analysis of 208
studies on number of incidences of AEs also found no significant difference between probiotics
and control (RR=1.00, 95%CI, 0.93 to 1.07). Collectively, these analyses indicated no difference
between probiotic and control in the quantity of AEs or the number of people who experienced an
AEs. When meta-analyses were run separately for different AE outcomes there was still no
difference between probiotic and control. Specifically, meta-analysis of 126 parallel RCTs saw no
difference in rate of GI AEs (RR=1.03, 95%CI, 0.89 to 1.18), meta-analysis of 65 parallel RCTs
for all incidences of infection saw no significant difference between treatment and control
(RR=1.00, 95%CI, 0.87 to 1.16). There remained no difference between treatment and control for
AEs when only studies with generally healthy subjects and subjects with health conditions were
analyzed separately or when meta-regression analysis as a function of health status was run.
Authors then evaluated 43 described cases of adverse events. Authors described the events as
rare events but of clinical importance. The risk was fungemia with presence of Saccharomyces
boulardii/cervisiae in blood cultures in 33 cases and eight cases of bacteremia from
Lactobacillus acidophillus/casei/rhamnosus GG and sepsis in nine cases linked to S. boulardii,
Lactobacills rhamnosus GG, Bacillus subtilis, Bifidobacteria breve. Other case reports also
described D-lactic acidosis associated with Lactobacilllus alone or blended with Bifidobacteria or
a case of endocarditis, abscess, fever associated with Lactobacillus or S. boulardii. The
individuals in the case reports were critically ill/high risk patients before they were treated with
probiotics. Only one person in the case reports was deemed generally healthy before developing
infection. An additional 36 trials monitored for fungemia, bacteremia, sepsis but did not find
infections from probiotics. The RCTs, CCTs or case series also did not produce evidence
suggesting a risk of acquired/transferable antibiotic/antifungal resistance. However, six case
reports suggested this could be a risk. Collectively, these described critically ill/high risk patients
(i.e. immunocompromised with recurrent septicemia, neonate with omphalocele, patient with
cancer, patient in ICU, patient with diabetes) who were administered Lactobacillus rhamnosus,
Bacillus subtilis, Bifidobacteria, S. boulardii, and developed infections such as abscess,
septicemia, fungemia and it was found that the probiotic that was isolated from the infections
was resistant to various antibiotics. However, in each case a different antibiotic was found that
the infection responded to and the individual recovered. The authors noted that while controlled
trials have not demonstrated a statistically significant increased risk of adverse events in healthy
or ill populations, there are case reports of individuals with existing health issues that have
developed probiotic-associated infections. The authors stated that because so few of the
published RCTs published evaluated safety as a primary outcome, there is insufficient
information to conclude on safety with confidence. They stated that results from the case reports
of infection from probiotics in vulnerable groups are an indication of a potential concern in some
populations.
References

1. Lee TT, Morisset M, Astier C, Moneret-Vautrin DA, Cordebar V, Beaudouin E, et al.
Contamination of probiotic preparations with milk allergens can cause anaphylaxis in children
with cow's milk allergy. J Allergy Clin Immunol. 2007 Mar;119(3):746-7. Epub 2007 Jan 30.
Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/17270264
2. Martín-Muñoz MF, Fortuni M, Caminoa M, Belver T, Quirce S, Caballero T. Anaphylactic reaction
to probiotics. Cow's milk and hen's egg allergens in probiotic compounds. Pediatr Allergy
Immunol. 2012 Dec;23(8):778-84. doi: 10.1111/j.1399-3038.2012.01338.x. Epub 2012 Sep 9.
3. Didari T, Solki S, Mozaffari S, Nikfar S, Abdollahi M. A systematic review of the safety of
probiotics. Expert Opin Drug Saf. 2014 Feb;13(2):227-39. doi: 10.1517/14740338.2014.872627.
Epub 2014 Jan 3. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/24405164
4. Whelan K, Myers CE. Safety of probiotics in patients receiving nutritional support: a systematic
review of case reports, randomized controlled trials, and nonrandomized trials. Am J Clin Nutr.
2010 Mar;91(3):687-703. doi: 10.3945/ajcn.2009.28759. Epub 2010 Jan 20. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/20089732
5. Hempel S, Newberry S, Ruelaz A, Wang Z, Miles JN, Suttorp MJ, et al. Safety of probiotics used
to reduce risk and prevent or treat disease. Evid Rep Technol Assess (Full Rep). 2011 Apr;
(200):1-645. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/23126627
Summary of Recommendations and Evidence

Allergic Disease - Probiotics and Prebiotics Summary of Recommendations and Evidence
Last Updated: 2019-01-29
This Summary of Recommendations and Evidence synthesizes the Key Practice Point(s) for each
Practice Question (PQ) in this Knowledge Pathway. It is organized by the Nutrition Care Process and
contains statements or recommendations that have been graded using either
the PEN or GRADE approaches to critical appraisal. For additional information on the evidence and
references, see the PQs in this Knowledge Pathway.
Content
INTERVENTION
1. Safety and Efficacy of Probiotic Supplementation for the Treatment of Eczema
1. Safety and Efficacy of Probiotic Supplementation for the Treatment of Eczema

Recommendation
Currently available probiotic strains (mostly Lactobacillus species but some Bifidobacteria species)
probably do not have much effect on parent- or patient-rated eczema symptoms or quality of life. They
may have a small, but clinically uncertain, benefit on investigator-rated eczema severity score after
supplementation, and eczema severity and number of flares over the month or two after supplementation
ends. However, in the studies examined, the probiotic supplements were well tolerated with no more

adverse effects reported with probiotics than with control/placebo. Only a few studies were low risk of bias
and many were of short duration; more research of longer duration and higher quality is needed to confirm
whether probiotics can or cannot help treat eczema.
Evidence Summary
Toggle content
Remarks
While it has been shown that the nature or composition of the microbiome is different in those with
eczema versus those without (such as lower bifidobacteria presence with eczema and progressively lower
bifidobacterial with progressively more severe eczema) it is not yet clear if supplementation can alter this
and then subsequently impact other body systems such as the skin and/or the immune system and then
impact eczema presence or severity. Nor is it known how long treatment would need to be in order to elicit
change, if possible.
Additional Remarks
Toggle content
Background
Probiotics Background
Last Updated: 2010-02-09

Are probiotics from food and supplements equally effective?
No general recommendation can be made. Most health-related effects of probiotics are thought to be
strain specific, therefore efficacy cannot be determined unless the food or supplement has been
appropriately tested in the form in which they are sold (1) or if bioequivalency has been demonstrated. It is
not possible to generalize a minimum dose of probiotics, as dosage varies for different probiotic strains
and the health effect being investigated (2),
Studies showing positive effects at levels below 108 CFU are uncommon in the literature therefore it is
believed that levels provided at a higher dose are needed for health effects (2).
What should consumers look for when choosing probiotic supplements?

NHPD regulations require the following on the product label:
product name
quantity of product in the bottle
recommended conditions of use, including dosage form, route of administration, and
recommended dose.
There are reports in the literature where products fail to meet the label claims with regard to levels of live
micro-organisms contained in the product (3,4). A Canadian study assessed whether commercially
prepared probiotic products contained viable organisms, as claimed by the manufacturers (4). The design
was a randomized, double-blind trial of 10 brands of probiotic preparations bought over-the-counter in

British Columbia's lower mainland. Only products claiming to contain Lactobacillus were included in the
study. The study measured the viable organisms in each probiotic brand and quantities of Lactobacillus in
each product. The results showed that none of the 10 products tested matched the amounts of probiotics
reported on their labels and two brands appeared to contain no viable probiotics. No lactobacilli grew in five
brands, although their labels stated that this was the main species. Eight brands contained viable cells,
but only 10% of the number stated by their manufacturers. Most product labels did not adequately identify
or quantify microbes.
Should probiotics always be refrigerated?

There are refrigerated food products containing probiotics, as well as freeze- dried supplements. The
freeze-dried supplements do not have to be refrigerated, but as a cautionary measure some manufacturers
recommended that they be refrigerated to assist in maintaining the viable counts. The shelf-life for
refrigerated food products containing probiotics ranges from three to six weeks (5). The shelf-life of dried
supplements is about twelve months. However, the viable counts of the probiotic micro-organisms may
decrease significantly during this time (5).
Should probiotics have a best before date?

Yes - a significant issue for probiotic supplements is the viability of the bacteria in the product. Most
products only claim the amount present “at the time of manufacture” which seldom reflects the content by
the time the consumer purchases it. Choose products from manufacturers that are labeled for viability
“through the end of shelf life” and not “at time of manufacture” (2).
Is there a way to tell if the cultures are still alive?

No, not unless microbiological testing is carried out on the product.
Do probiotics survive passage through the stomach?

In order for microorganisms to be classified as probiotics, they must meet several criteria. These criteria
include (6):
the ability to withstand and survive the effect of gastric acid, biliary secretions and pancreatic
secretions in order to reach the small and large intestine intact
be non-pathogenic and non-toxic
remain viable during transport and storage
exert beneficial effects on the host
stabilize the intestinal microflora
adhere to the intestinal epithelial cell lining
produce antimicrobial substances against pathogens.
It is important to note that a host of products called probiotics are commercially available but are not truly
probiotic. Clinical research evidence that they effectively meet the criteria listed above is needed to identify
true probiotics (1).
Do all probiotics function in the body in the same way?

No, the way they function in the human body is thought to be strain specific although this may not be the
case for all applications.

What products are available in Canada?
For an overview of probiotics and so-called ‘probiotics’ potentially being used in Canada, click here.
Additional Reading
1. Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the risks?
Am J Clin Nutr. 2006 Jun;83(6):1256-64. Abstract available from:
2. Douglas LC, Sanders ME. Probiotics and prebiotics in dietetics practice. J Am Diet Assoc. 2008
Mar;108(3):510-21. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/18313433
3. Floch MH, Madsen KK, Jenkins DJ, Guandalini S, Katz JA, Onderdonk A, et al.
Recommendations for probiotic use. J Clin Gastroenterol. 2006 Mar;40(3):275-8. Abstract
available from: https://www.ncbi.nlm.nih.gov/pubmed/16633136
4. Reid G, Anukam K, Koyama T. Probiotic products in Canada with clinical evidence: what can
gastroenterologists recommend? Can J Gastroenterol. 2008 Feb;22(2):169-75. Abstract available
at: https://www.ncbi.nlm.nih.gov/pubmed/18299736
References
1. Reid G, Anukam K, Koyama T. Probiotic products in Canada with clinical evidence: what can
gastroenterologists recommend? Can J Gastroenterol. 2008 Feb;22(2):169-75. Abstract available
at: https://www.ncbi.nlm.nih.gov/pubmed/18299736
2. Douglas LC, Sanders ME. Probiotics and prebiotics in dietetics practice. J Am Diet Assoc. 2008
Mar [cited 2009 1 Mar];108(3):510-21. Abstract available from:
3. Sanders ME, Walker DC, Walker KM, Aoyama D, Klaenhammer TR. Performance of
commercial cultures in fluid milk applications. J Dairy Sci. 1996 [cited 2007 6 Jan],79(6),:943-55.
4. Huff BA. Caveat emptor. "Probiotics" might not be what they seem. Can Fam Physician. 2004
[cited 2007 6 Jan];50:583-7. Abstract available from:
5. Kopp-Hoolihan L. Prophylactic and therapeutic uses of probiotics: a review. J Am Diet Assoc.
2001 Feb [cited 2007 6 Jan];101(2):229-38; quiz 239-41. Abstract available from:
6. Tomasik PJ, Tomasik P.. Probiotics and prebiotics. Cereal Chemistry. 2003 [cited 2007 6
Jan];80(2):113-7. Available from: http://cerealchemistry.aaccnet.org/doi/abs/10.1094/CCHEM-08-
11-0100
Disclaimer: The information included on this website is based on the best available evidence at the time of writing. It

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protocols, to assist practitioners to make practice decisions. It should be used to complement, not replace, sound clinical
judgment. While every effort is made to ensure information contained on this website is accurate and up-to-date, errors
may occasionally occur. Neither Dietitians of Canada nor any dietetic associations contributing to or licensing the content
in PEN: Practice-based Evidence in Nutrition® assumes any responsibility or liability arising from any error in or omission
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professional. Because PEN® content is updated regularly, printed web pages or PDF documents may become obsolete.
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