jurriaan mes wageningen ur - food & biobased research...
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New perspectives on the link between
nutrition and the immune system
Jurriaan Mes
Wageningen UR - Food & Biobased Research
Nutritional factors that received an authorised health claims
regarding immune function:
● Copper, Iron, Zinc, Selenium
● Folate
● Vitamin A
● Vitamin B12
● Vitamin B6
● Vitamin D
● Vitamin C (2x)
● contributes to the normal function of the immune system
● contributes to maintain the normal function of the immune system during and after intense physical exercise
Current nutritions with immune health effects
Product launched with link to immune based
on these vitamins and minerals
EFSA guidelines leading
Approved compounds on vaccination effect
Savy M, et al. 2009 Landscape analysis of interactions
between nutrition and vaccine responses in children. J Nutr
139:2154S-218S.
● Evidence for definitive adjunctive effects of micronutrient
supplementation at the time of vaccination is also weak.
● No evidence for an effect of Vitamin A supplementation on
specific responses to diphtheria and tetanus, cholera, influenza,
Haemophilus influenza type b and pneumococcal vaccines.
Habib et al (2015) Zinc supplementation fails to increase the
immunogenicity of oral poliovirus vaccine: a randomized
controlled trial. 33(6):819-25.
Many more examples
Some general designs
Population: elderly
● Expected a more senescent immune system
● But very heterogeneous group
Common vaccination model
● More appealing to the general community
Often these studies are small
● <40
Analysis
● Often based on many markers – pilot trial – (need correction
multiples testing)
● Low in confirmative trials – one primary outcome
(preferred by EFSA)
Study related to support vaccination PS
Study related to support vaccination Lb
Akatsu H, et al 2013. Lactobacillus in jelly enhances the effect of influenza vaccination in elderly individuals. J Am Geriatr Soc. 2013 Oct;61(10):1828-30.
Study related to support vaccination Lb
Roman BE, Beli E, Duriancik DM, Gardner EM. 2013 Short-term supplementation with active hexose correlated compound improves the antibody response to influenza B vaccine. Nutr Res. 33(1):12-7.
Study related to immune support wolfberry
milk-based wolfberry formulation (Lacto-Wolfberry)
150 Chinese elderly (65–70 years old) supplemented with Lacto-Wolfberry or
placebo (13.7 grams/day)
IgG levels responded significantly different
Not known effect to separate vaccines
But no significant changes in many cellular parameters, DHT, inflammatory
markers, symptoms
Vidal et al (2012) Immunomodulatory effects of dietary supplementation with a milk-based wolfberry formulation in healthy elderly: a randomized, double-blind, placebo-controlled trial. Rejuvenation Res. 15(1):89-97.
Study related to immune support Lb
Jespersen 2015. Am J Clin Nutr. 101(6):1188-96.
Reaching enough illness symptoms (checked by practitioner) requires
large group and or long intervention period and or heavy
challenge period.
Shift to other vaccine models ?
Mwanza-Lisulo M, Kelly P. Potential for use of retinoic acid as an oral vaccine adjuvant. Philos Trans R Soc Lond B Biol Sci. 2015 Jun 19;370(1671).
Effect all-trans retinoic acid in oral typhoid
vaccination
Lisulo MM, et al. (2014) Adjuvant potential of low dose all-trans retinoic acid during oral typhoid vaccination in Zambian men. Clin Exp Immunol. 175(3):468-75.
Whole gut lavage fluid (WGLF) – local production need to flush out
Relation fruit & vegetable intake on vaccination
History dependent response
on IgG sab
But not on tetanus
Gibson et al 2012. Effect of fruit and vegetable consumption on immune function in older people: a randomized controlled trial. Am J Clin Nutr. 96(6):1429-36.
Tips and tricks
Subjets not exposed to vaccination model before?
● Or use memory cell population as new type of read out
Select vaccine on potential mechanism
● T cell dependent/independent
● Th1/Th2 directed
Use suboptimal doses
● Study dynamics of the response
● Window of improvement
Preferable use vaccine with definitions of normal levels of antibody response and protected levels
Make trial large and dedicated (if want to convince EFSA)
Gut innate immune system important
‘Leaky gut syndrome’ is a hypothetical condition that might be related to chronical diseases (Metabolic Syndrome, T2D, lupus, Multiple Sclerosis, migraines, autism etc).
‘dysfunctional gut syndrome’
● Malabsorption
● Abnormal hormonal signalling
● Mucosal barrier
● Local and systemic challenge by bacterial, endotoxins, PAMPs/MAMPs etc
● Local and systemic challenge by proteins/ epitopes trigger immune responses
www.schneiderclinic.com
Leaky is not only in between cells
Price et al (2013) Nuts 'n' guts: transport of food allergens across the intestinal epithelium. Asia Pac Allergy. 3(4):257-265.
Ghoshal S, et al (2009) Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res. 50(1):90-7.
Jialal I, Rajamani U. (2014) Endotoxemia of metabolic syndrome: a pivotal mediator of meta-inflammation. Metab Syndr Relat Disord. 12(9):454-6.
Markers to study gut/barrier function
Potential markers to use
● Sugar probes - Sucrose, Lactulose,
rhamnose, Sucralose, Erythritol
● Gut permeability – Zonulin, iFABP, CLDNs
● Endotoxines levels - LPS, LBP, CD14
● PAMPs, bacterial – DNA, flagella, peptidoglycans, etc
● Cholesterol metabolism - HDL/LDL/apoB
● Inflammatory markers – hsCRP, IL-6, TNF-α, calprotectin, α1-antitrypsin
● Food compounds – e.g. peanut allergen
● Others for specific (metabolic) functions to develop
An example with Probiotic mixture
Van Hemert et al (2013) Advances in Microbiology 3, 212-221
Some factors to keep in mind
Sample collection can influence outcome
● Faecal samples – random
● Urine – moderate dynamics, 0-5h, 5-24h
● Serum – overnight fasted or dynamics (area under the curve)
Use of challenge models
● NSAIDs – ibuprofen
● High fat, high sugar, or together (PhenFlex)
● Vary in type of fat (sat, mono-un, poly-un)
Future perspectives to study nutrition and immune support
Need to understand personal immune status
Need to identify key biomarkers
Personalized risk assessment model (+ nutrient based advices)
Castiglione et al. JMIR Res Protoc. 2013 Oct 31;2(2):e44.
acute challenge
Gut function
and microbiot
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Stress and chronic
inflammation
related challenges
Systemic and
Metabolic Related
processes
Physical Activity
Immune status
Immune status risk assessment
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Nutrients
Age
Thank you for
the attention