Probiotic Effects on Immune

Related Diseases and Immune

Mediated Mechanisms
Presented by Ana Sesatty, Dietetic Intern
November 30,2015

INTRODUCTION

Probiotics are live bacterial or yeast microorganisms

Main families include Saccharomyces, Lactobacillus, and Bifidobacteria

Probiotics found in foods

More than 400 species

Yogurt, fermented milk, cheeses, and kefir

Dietary probiotic supplements

Different doses and strains

Introduce beneficial bacteria or yeast

Restore and/or maintain intestinal microbial balance

Growing interest in therapeutic uses and mechanisms of probiotics

SCIENTIFIC HISTORY

Discovered in 1907 by Russian scientist Eli Metchnikoff

Studied Bulgarian peasant population

Associated regular consumption of fermented dairy products with enhanced

longevity and health

Attributed beneficial effects to lactic acid bacteria

Believed in intestinal toxic bacteria contributing to aging and disease

Believed in the modification of intestinal microflora

By replacing harmful with beneficial bacteria

Spent his life studying health benefits of lactic acid bacteria

SCIENTIFIC HISTORY

Eli Metchnikoffs microbial concept

abandoned from 1908 to 1964

Antibiotics discovered in 1928

1965: Lilly and Stillwell (57 yrs

later)

First to use term probiotics to

define organisms that secreted
substances which stimulated
growth of other organisms

probiotic term to define

organisms and substances that
contributed to intestinal microbial
balance

probiotic term to define live

microorganisms which benefited
the host by enhancing intestinal
microbial balance

2001: United Nations Food and Agriculture Organization/World Health

Organization

Adopted probiotic definition as

live microorganisms which when
administered in adequate amounts
confer a health benefit on the
host

Contributed to the prominence of

probiotic research in the last 15 yrs

1974: Parker (9 yrs later)

1989: Fuller (15 yrs later)

INTERNET AND MEDIA COVERAGE

Increasing and vast amount of coverage

Common probiotic topics

health benefits, side effects, weight loss, supplements, and brands

Promote probiotics as a miracle cure for a variety of medical conditions

May misrepresent scientific data and correlations

Publicize preliminary findings as proven facts

Misleading to the public

Probiotic products sales in North America increased from $2.6 billion in 2010 to
$3.3 billion in 2014

Probiotic Therapeutic Uses in

Immune Related Diseases
Inflammatory bowel diseases (IBD), antibiotic-associated diarrhea (AAD),
and food allergies

INFLAMMATORY BOWEL DISEASE (IBD)

Crohns disease (CD)

Ulcerative Colitis (UC)

Studies show mixed results

Most studies show no benefits of

probiotic interventions

A few studies show no benefits of

probiotic interventions

Review of randomized clinical trials (RCT) results

Only 3 out of 14 RCT studies

supported positive findings using
probiotics to treat and maintain
disease remission.

Further studies are needed to determine probiotic effectiveness

Strong evidence supports probiotic interventions

Review of randomized clinical trials (RCT) results

19 out of 21 RCT studies supported

positive findings using probiotics to
reduce clinical symptoms, and
induce or maintain disease
remission.
Evidence suggests the use of a multi-strain probiotic and standard
therapy to be beneficial

ANTIBIOTIC-ASSOCIATED DIARRHEA (AAD)

Most common cause of AAD is Clostridium difficile infection

Studies are limited with mixed results

Study in hospital patients 65 yrs and older

Multi-strain probiotic of lactobacilli and bifidobacteria (6 x 10 10 CFUs) for 21 days

Probiotic supplementation was not effective in preventing AAD

Study in hospital patients receiving antibiotics

A high and low dose of multi-strain probiotic of lactobacilli and bifidobacteria for 7 days

High dose was 1.70 x 10 10 CFUs and low dose was 4.17 x 10 9 CFUs

High dose associated with lower AAD occurrence, C. diffile diarrhea, and
gastrointestinal symptoms

Scientific evidence is inconclusive and further studies are needed to determine

the effectiveness of probiotics in preventing AAD

FOOD ALLERGIES

Studies are limited with mixed

results

Study in infants with cows milk

allergy

Lactobacillus casei and

Bifidobacterium lactis with
hydrolyzed formula for 12 months
Probiotic supplementation failed to
induce cows milk tolerance

Study in infants with cows milk

alergy

Lactobacillus GG (1.4 x 107 CFUs)

for 12 months

Probiotic supplementation
accelerated cows milk tolerance

Study in children with peanut allergy

Lactobacillus rhamnosus (2 x 1010

CFUs) for 18 months

Peanut oral immunotherapy (OIT)

Probiotic supplementation with

peanut OIT reduced peanut skin
prick test responsiveness and IgE
levels

Scientific evidence is inconclusive

Further studies are needed to determine the effectiveness of

probiotics in preventing in preventing, attenuating, and treating food
allergic reactions

Probiotic Immune Mediated

Mechanisms
Toll-like receptors and NOD-like receptors

TOLL-LIKE RECEPTORS AND

PROBIOTICS

TLRs recognize pathogenicassociated molecular

patterns (PAMPs) and trigger
innate immunity response

Proposed mechanism

Probiotics activate TLRs

Releasing of cytokines

Triggers a controlled
response in dendritic
cell

Dendritic cell signals

differentiation of T
helper cells resulting in
the production of Treg

Upregulation of
cytokines

Inhibits production of
Th1, Th2, and TH17 and
subsequent
inflammatory response

NOD-LIKE RECEPTORS (NLRs)

AND PROBIOTICS

NLRs recognize pathogenicassociated molecular patterns

(PAMPs) and trigger innate
immunity response

Proposed mechanism in CD

Bacterial invasion due to a

lack of defensins (host
defense peptides)

NOD2 receptors do not

recognize bacteria

Bacteria enters the

dendritic cell activating
macrophages

Excessive proinflammatory
cytokine production

Probiotics induce and

upregulate defensins
production

Inhibits bacteria from

entering the dendritic cell
and subsequent
inflammatory response

CONCLUSION

Probiotics are difficult to research

Different strains, doses, populations, diseases and genetic variability

Scientific evidence on probiotic therapeutic uses in immune related

diseases remains limited with mixed results and is inconclusive

Probiotic immune-mediated mechanisms are poorly understood with

limited studies

Further studies are needed to determine the effectiveness of

probiotics in immune related diseases and underlying immunemediated mechanisms

MY PROFESSIONAL RECOMMENDATIONS

No official nutrition guidelines on the use of probiotics

Do not recommend the use of probiotics alone to prevent, attenuate,

or treat immune related diseases

Recommend probiotics in combination with standard treatments

Do not recommend probiotics in immunosuppressed patients

Recommend probiotics to healthy individuals

Recommend to obtain probiotics from food instead of supplements

When using probiotic supplements would recommend to look at the

dose, strain, quantity, quality, and package information

Discuss evidence is inconclusive, further studies are needed, and

reported side effects

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