probiotics from foods to supplements a scientific point of vie · 2015-12-03 · dietary...

“The Global Voice of Probiotics”“The Global Voice of Probiotics”

Probiotics from foods to supplements a scientific point of view

“The Global Voice of Probiotics”“The Global Voice of Probiotics”

Arthur OuwehandResearch Manager/Technical Research FellowDuPont Nutrition & Health, Kantvik, FinlandIPA/IPA Europe Scientific Advisory Board

ILSI Europe Probiotic Task Force

DuPont Nutrition & HealthLegacy Danisco, Legacy Solae

Probiotics, starter cultures, Prebiotics, Fibre, Sweeteners, Soy Proteins

“The Global Voice of Probiotics”

Todays topics:� When is a product or microbe a probiotic and when not

� What to expect from these products and what not

� Combining probiotic strains

� Modulating microbiota with probiotics

“The Global Voice of Probiotics”“The Global Voice of Probiotics”

Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (Hill et al. 2014)

☺ Lactobacillus sp.

☺ Bifidobacterium sp.

☺ E. coli, Enterococcus, yeast, Bacillus, .........

What are probiotics?

“The Global Voice of Probiotics”“The Global Voice of Probiotics”

Faecal

transplant

Fermented

foods

Probiotic

foods

Probiotic

dietary supplements

Probiotic

medical foods

Probiotic

medical device

Probiotic

pharmaceuticalsprobiotic

not

probiotic

Yogurt

Cheese

Sourkraut

Tempé

Natto

.............

• Foods that contain live microbes are not necessarily probiotic• These foods may be healthy, but that does not make them probiotic

When is a product a probiotic

and when not?

“The Global Voice of Probiotics”“The Global Voice of Probiotics”

Faecal

transplant

Fermented

foods

Probiotic

foods

Probiotic

dietary supplements

Probiotic

medical foods

Probiotic

medical device

Probiotic

pharmaceuticalsprobiotic

not

probiotic

probiotic

• Maintain health

• Promote/support health

• Reduce risk for disease

(not prevent)

• Prevent disease

• Cure disease

• Mitigate disease

When is a product a probiotic

and when not?

“The Global Voice of Probiotics”

Example of risk reductionRespiratory tract infection (duration)

King et al. Br. J. Nutr. 2014

“The Global Voice of Probiotics”

Example of risk reductionRespiratory tract infection (incidence)

West et al.Clin. Nutr. 2013

“The Global Voice of Probiotics”

Example of risk reductionRespiratory tract infection (incidence)

Respiratory tract infection

Respiratory tract infection

Respiratory tract infection

Placebo

Probiotic

“The Global Voice of Probiotics”

Example of risk reductionAntibiotic Associated Diarrhoea

Pattani et al. Open Med. 2013

“The Global Voice of Probiotics”

Example of risk reductionAtopic Dermatitits

Wickens et al. Clin. Exp. Allergy2013

“The Global Voice of Probiotics”

Example of risk reductionAtopic Dermatitis; reduced severity

Wickens et al. Clin. Exp. Allergy2013

“The Global Voice of Probiotics”

Summarise� Probiotics are live microbes; not all live microbes are

probiotics

� Probiotics can be drugs, here we talk about dietary supplements and functional foods

� Maintain health, reduce risk (not prevent)

“The Global Voice of Probiotics”

Probiotics; alone or together?

� Mono-strain probiotics

� Multi-strain probiotics

� Multi-species probiotics (is also multi-strain)

“The Global Voice of Probiotics”

Probiotics; why mix?

� Combine the benefits of different strains

� More diversity is better

� Seek synergies

� ..........

� Up to each manufacturer to document this

“The Global Voice of Probiotics”

Probiotics; why mix?

Chapman et al. 2011

“The Global Voice of Probiotics”“The Global Voice of Probiotics”

Antimicrobial activity; single or multipleC. difficile E. coli S. Typhimurium

Lactobacillusmix vs. single

No difference Mix>single(p>0.01)

No difference

Bifidobacteriummix vs. single

Mix>single(p>0.0001)

Mix>single(p>0.05)

No difference

Multigenusmix vs. Lactobacillus

Mix>single(p>0.0001)

No difference Mix>single(p>0.0001)

Multigenusmix vs. Bifidobacterium

Mix>single(p>0.0001)

No difference Mix>single(p>0.0001)

Chapman et al. 2012

“The Global Voice of Probiotics”

Probiotics; why mix?

� Combine the benefits of different strains

� More diversity is better

� Seek synergies

� ..........

� Up to each manufacturer to document this

� Antagonism?

“The Global Voice of Probiotics”

Antimicrobial effect of probiotics

Wells et al. 1997

Lactobacillus fermentum

Streptococcus bovis

“The Global Voice of Probiotics”

Antagonism between mixed probiotics?

� Effect of probiotics on serum cholesterol

� Single strain (4 studies) -0.22 (95% CI; -0.65, 0.21)

� Multiple strain (6 studies) -0.31 (95% CI; -0.47, -0.16)***

� P-value between variables = 0.69

� Effect of probiotics on serum LDL-cholesterol

� Single strain (6 studies) -0.34 (95% CI; -0.68, 0.00)**

� Multiple strain (4 studies) -0.52 (95% CI; -0.85, -0.18)***

� P-value between variables = 0.47

� No difference between single and multiple strain

Sun & Buys 2015

“The Global Voice of Probiotics”

Antagonism between mixed probiotics?

� Effect of probiotics on diastolic blood pressure

� Single strain (4 studies) -0.28 (95% CI; -2.95, 2.39)

� Multiple strain (5 studies) -5.79 (95% CI; -8.66, -2.93)**

� P-value between variables <0.05

� Effect of probiotics on systolic blood pressure

� Single strain (4 studies) -1.99 (95% CI; -4.79, 0.81)

� Multiple strain (4 studies) -2.72 (95% CI; -4.35, -1.08)**

� P-value between variables <0.05

� Difference; multiple strain better

Khalesi et al. 2014

“The Global Voice of Probiotics”

Antagonism between mixed probiotics?

� Effect of probiotics on gastrointestinal diseases

� Single strain (51 studies) 0.63 (95% CI; 0.53, 0.76)**

� Multiple strain (33 studies) 0.73 (95% CI; 0.68, 0.79)**

� P-value between variables > 0.05

� No difference between single and multiple strain

Ritchie & Romanuk 2012

“The Global Voice of Probiotics”

Antagonism between mixed probiotics?

Pro-inflammatory and anti-inflammatory may cancel out in a mixture (in vitro). Biomarker, not clinical end-point

Timmerman et al. 2007

“The Global Voice of Probiotics”

Antagonism between mixed probiotics?� Effect of probiotics on experimental pancreatitis (= disease)

� Histopathology of pancreas

� Single strain (3 studies) -2.240 (-3.686, -0.794)**

� Multiple strain (3 studies) -0.503 (-1.893. 0.888)

� Bacterial translocation to pancreas

� Single strain (2 studies) 0.123 (0.011, 1.416)*

� Multiple strain (3 studies) 0.359 (0.047, 2.714)

� Bacterial translocation to mesenteric lymphe nodes

� Single strain (2 studies) 0.147 (0.041, 0.529)**

� Multiple strain (3 studies) 0.371 (0.122, 1.133)*

� Difference; multiple strain worse (only example)Hooijmans et al. 2012

“The Global Voice of Probiotics”

Single vs. Multiple strain

� What meta-analyses compare:

� Single strain (A) vs. Multiple strain (B + C)

� vs.

� What should be compared:

� Single strains (A, B) vs. their combination (A + B)

� vs. vs.

“The Global Voice of Probiotics”

Reduction in respiratory tract infection in children during the winter

Leyer et al. 2009

“The Global Voice of Probiotics”

Summarise� Combining probiotic strains does not affect efficacy in

most cases

� In some cases it may even improve efficacy

� In vitro, immune effects on defined biomarkers may cancel out each other

� Only in one case (disease), effects maybe reduced in a mixture

� Head-on comparisons are, however, few and do not show a negative interaction

“The Global Voice of Probiotics”

Probiotics:modulating intestinal microbiota

Durban et al. 2012

“The Global Voice of Probiotics”

Probiotics:modulating intestinal microbiota

Jalanka-Tuovinen et al. 2011

“The Global Voice of Probiotics”

Probiotics:modulating intestinal microbiota

Ottman et al. 2012

“The Global Voice of Probiotics”

Probiotics:modulating intestinal microbiota

� Intestinal microbiota is in practice faecal microbiota

� ’The intestinal microbiota’ does not exist

� Intestinal microbiota is highly personal

� Fairly stable over time (days-months), but changes during life

� Variation over time is smaller then variation between subjects

� Health benefits without modulating microbiota

� How to stabilise/improve/modulate the intestinal microbiota in healthy subjects?

“The Global Voice of Probiotics”

Maintain/restore microbiota during stress

Seven day antibiotic

treatment; influence

on selected

intestinal microbial

groups

Rashid et al. 2015

“The Global Voice of Probiotics”

Summarise� A healthy subject has a stable microbiota

� The microbiota is very personal

� What is a healthy microbiota?

� Probably the microbiota you have when you are healthy

� Improving the microbiota is probably not possible and possibly undesirable

� Feasible target: maintain microbiota during stress or restore after stress

� Other health targets?

“The Global Voice of Probiotics”

Conclusions� Probiotics are live microbes; not all live microbes are

probiotics

� Probiotics can be drugs, here we talk about dietary supplements and functional foods

� Maintain health, reduce risk (not prevent)

� Most cases, combining probiotics does not negatively affect activity

� Improving the microbiota of a healthy subject is challenging

� Instead, maintain or restore original microbiota

� Consider other health targets?