microbiota en gedrag
TRANSCRIPT
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Het effect van het microbioom op gedrag – van wetenschap naar praktijk (en weer terug)
Koen Venema
Beneficial Microbes Consultancy, Wageningen, The
Netherlands, [email protected]
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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• initiator and organisor of the
Beneficial Microbes Conference series
• editor-in-chief of the journal
Beneficial Microbes
• founder and CEO of
Beneficial Microbes Consultancy
2008 2010
2012
10-12 Oct. 2016
2015
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Waar gaan we het vandaag over hebben?
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Tijdens deze gast lezing zal ik een uitleggen wat microbiota en
probiotica zijn en doen en tevens uitleggen waarom het nodig is om in
multidisciplinaire teams de rol van de microbiota en probiotica op
moderne ziektes en aandoeningen, zoals overgewicht, allergiën,
inflammatoire ziektes, autisme, gedrag, depressie, etc., te onderzoeken.
Verwacht een combi van een klein beetje hard-core science met enkele
interessante feiten en af en toe wat humor.
“If you don't like bacteria, you're on the wrong planet.”
― Stewart Brand
“Wanneer je al het meercellige leven van de aarde zou
wegvagen, zou het microbiële leven waarschijnlijk een
klein beetje verschuiven. Verdwijnt het microbiële
leven, dan betekent dat de onmiddelijke dood voor
onze planeet.”
― Carl Woese
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Als kinderen geboren worden, komen ze uit een relatief steriele omgeving van de baarmoeder in een wereld vol met bacteriën…
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Script van deel 1 van de presentatie
Microbiota
aandacht in de wetenschap
rol van microbiota bij ziekte en gezondheid
hoe ziet onze microbiota er nu uit?
ontwikkeling microbiota van jong tot oud
probiotica
prebiotica
feces transplantatie (repoopulate)
niet alle probiotica zijn hetzelfde
Take home messages deel 1
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Microbiota in de (wetenschappelijke) pers
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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.... want de microbiota is betrokken bij:
- colon kanker
- inflammatory bowel disease (IBD)
- allergie (huid, luchtwegen)
- overgewicht
- type I en II diabetes
- levensduur
- prikkelbaar darm syndroom (IBS)
- angst en depressie
- brein ontwikkeling en cognitie
- autisme
- Parkinson’s
- Alzheimer’s
- .....
Probiotics and Prebiotics
Current Research and Future Trends
2015. Eds. K. Venema & A.P. do Carmo
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Het aantal bacteriën in de darm is 10x zo veel als onze eigen lichaamscellen Volwassenen kunnen ~ 1 kg darmbacteriën met zich meedragen We deponeren per jaar ons eigen gewicht aan bacteriën in het toilet Als we 70 zijn komt dat overeen met 12 olifanten > 50% van feces is bacteriën (natgewicht) Elk persoon heeft meer darm bacteriën dan het aantal mensen dat er ooit op deze planeet geleefd heeft 400 - >1000 species
“Soundbites”
Courtesy of Roderick Mackie / Glenn Gibson
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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De darm microbiota is noodzakelijk voor:
- ontwikkeling van de darm
- ontwikkelen en trainen van het immuun systeem (70% van het immuun systeem
zit in de darmen)
- het produceren van vitamines (o.a. vit. K)
- het produceren van zogenaamde korte-keten vetzuren (SCFA; azijnzuur,
propionzuur en boterzuur); waarvan boterzuur als meest belangrijkste geacht
wordt, omdat microbieel boterzuur verantwoordelijk is voor ~70% van de totale
energiebron van het epitheel van de dikke darm
- kolonisatie resistentie
- door competitie voor nutrienten
- door competitie voor aanhechtingsplaatsen
- door productie van SCFA, waardoor lage pH
- door productie bacteriocines
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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“Exposed to a world of micro-organisms”
• Totale oppervlak van de darm is de grootte van een tennis court
• Dus dit moet goed verdedigd worden tegen indringers
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Dit is waar uw lunch
nu is, met uw levende
bacteriele gasten
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Bacteriën strijden om de aanhechting aan darm-epitheel
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Als kinderen geboren worden, komen ze uit een relatief steriele omgeving van de baarmoeder in een wereld vol met bacteriën…
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Moedermelk als een bron van gezonde bacteriën
Probiotica
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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microbiota
verstoring
microbiota
verstoring
ontsteking
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Ziekte van Crohn
gereduceerde microbiele
genen diversiteit
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Microbiota en overgewicht/obesitas
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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microbiota
verstoring
microbiota
verstoring
overgewicht
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Kunnen we (een aantal van) die ziektes managen?
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Probiotics: definition
live microorganisms which, when administered in
adequate amounts, confer a health benefit on the host FAO/WHO 2001
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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<105
106
107
108
109
CF
U/m
l
Niet alle probiotica zijn gelijk! Slide van Ger Rijkers
#55
#22
#36
0 1 2 3 4 5 6 Time (hrs)
Lactobacillus acidophilus
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Hoe werken probiotica? Hoe kunnen op het brein inwerken als ze in de darm zitten?
barrier/
mucosal
integrity
lumen/
resilience
immune system dendritic cell
epithelial
cell
microbiota
probiotics
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Hoe kies je dan het juiste probiotica?
Courtesy of Ger Rijkers
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Hoe blijf je op de hoogte?
Welke publicaties zijn van goede kwaliteit?
Wat voor type bewijs is voldoende?
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Graad A
Graad B
Graad C
Graad D
Aanbeveling op basis van bewijs
Systematische review of meta-analyse
(minstens) 1 RCT
(minstens) 1 goed opgezette en
gecontroleerde studie
(minstens) 1 cohort studie
Goed opgezette beschrijvende
studies, case control, case series
Verslagen van expert comitees,
klinishe ervaring van experts
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Zijn DBPCRT altijd nodig? Double-Blind Placebo-Controlled Randomized Trials
Courtesy of Eric Claassen
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Zijn DBPCRT altijd nodig? Double-Blind Placebo-Controlled Randomized Trials
DBPCRT leveren graad A bewijs en zijn het meest overtuigend....
.... als ze op de juiste manier uitgevoerd worden!
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Prebiotics: definition
a selectively fermented ingredient *
that results in specific changes in
the composition and/or activity of
the gastrointestinal microbiota, thus
conferring benefit(s) upon host
health
* largely restricted to carbohydrates until now Blatchford, Venema and others 2014, Intl J Probiotics Prebiotics 8(4)
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Effect van probiotica op maagdarm ziektes
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Effect van soort probiotica n
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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■ genome stability
Sybesma et al. AEM 2013
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Antibiotica gebruik & C. difficile
C. difficile
bacterie
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• C. difficile vaak ongevoelig voor antibiotica
• dat is juist de reden dat na een antibioticum kuur C.diff
uitgroeit
• en is tegelijk de reden dat een volgende antibioticum kuur niet
goed helpt
• veel patienten hebben recidiverende C.diff infecties
• soms/vaak zijn die levensbedreigend
• vaak is dan de enige optie nog .....
• FECES TRANSPLANTATIE
• cure-rate van ~90% !!
• geen medicijn is zo goed !
Antibiotica gebruik & C. difficile
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Feces transplantaties.....
....
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Graad A
Graad B
Graad C
Graad D
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Do you (have to) believe what a company tells you?
Wanneer geen probiotica? immunocompromised?
kritiek zieke mensen?
zeer jong kinderen?
ouderen met een verminderde
weerstand?
zwangere vrouwen?
In veel van deze gevallen worden probiotica al
gebruikt.
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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understatement
Bij veel van de hedendaagse problemen kunnen probiotica een
gezonde bijdrage leveren
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Wrap up and Take home messages
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Conclusies Deel 1
• Probiotica werken! Maar het maakt
wel uit welke stam (of mengsel) je
kiest.
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Script van deel 2 van de presentatie
gut-brain axis
rol van microbiota
preclinische aanwijzingen
klinische studies
niet alle probiotica zijn hetzelfde
Take home messages deel 2
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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.... want de microbiota is betrokken bij:
- colon kanker
- inflammatory bowel disease (IBD)
- allergie (huid, luchtwegen)
- overgewicht
- type I en II diabetes
- levensduur
- prikkelbaar darm syndroom (IBS)
- brein ontwikkeling en cognitie
- autisme
- .....
control rat autistic rat
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Anxiety
BALB/c SPF mice w/o antibiotics
ATM = neomycin 5 mg/mL, bacitracin 5 mg/mL, and pimaricin 1.25 μg/mL After ATM: more explorative
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Anxiety
BALB/c SPF mice w/o antibiotics
After ATM: biochemical
changes in the brain. BDNF: Brain-derived neurotrophic factor,
a protein which is active in areas vital to
learning, memory, and higher thinking
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Anxiety – microbiota transplant
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Anxiety – microbiota transplant
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Birth delivery mode alters anxiety-like behaviour (8-9 wks)
Original setup
Natural birth Cross-fostered C-section
marble bury test
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Stress alters the gut-brain axis
cortisol
cytokines
adrenocorticotropic hormone
serotonin (5-HT)
barrier function of the gut
Increased permeability
translocation of endotoxin
increased colonic transit
mucosal inflammation
changes in colonic morphology
etc.
Altered levels and metabolism of:
Altered:
bi-directional
crosstalk
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Immune
O’Mahony et al. Psychopharmacology (2011)
Endocrine Visceral Pain
Open Field Increased colonic transit, intestinal permeability, mucosal inflammation, colonic
morphology (O’Malley et al., 2010, Stress)
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Autism Spectrum Disorders
control rat autistic rat + PA
Single intracerebroventricular (ICV)
infusions (4 µL of 0.26 M solution over
4 min) of propionic acid (PA)
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http://apc.ucc.ie
Desbonnet et al 2014
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Social deficit after propionate infusion
control rat autistic rat + PA
Single intracerebroventricular (ICV)
infusions (4 µL of 0.26 M solution over
4 min) of propionic acid (PA)
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Odds Ratio: 1.23
(1.07, 1.40)
1,191,920
participants,
12,897 of which
had ASD
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Parkinson’s disease
Parkinson’s disease is the second most common neurodegenerative disease and is characterized by region-specific loss of dopaminergic neuromelanin-containing neurons in the brain Parkinson’s disease patients suffer from gastrointestinal discomfort nearly half of all Parkinson’s disease patients report long-term constipation Parkinson’s disease patients had a significantly increased intestinal permeability Future studies might elucidate further links between gut and brain function in Parkinson’s disease, and should preferably comprise investigations of the gut microbiota. Pro- and/or prebiotics that strengthen the epithelial barrier function might be beneficial to these patients
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Amyloid protein precursor (APP) is a pivotal protein in the formation of the plaque-inducing amyloid-β protein, which causes neuronal degeneration in the brain of Alzheimer’s disease patients systemic administration of LPS in mice has been shown to increase APP expression and caused neuronal cell death significantly increased plasma levels of LPS in Alzheimer’s disease patients compared with healthy controls were detected, which might suggest that Alzheimer’s disease patients suffer from elevated intestinal permeability Pro and/or prebiotics that have an anti-inflammatory effect or reduce bacterial and/or LPS translocation might be beneficial for these patients
Alzheimer’s disease
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Probiotic alters GABA
receptors in various
brain areas
Bravo et al., PNAS Sept 2011
L. rhamnosus JB-1 reduces anxiety and
behavioural despair
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Defensive Marble Burying
Elevated Plus Maze
174 1205
Esc = escitalopram
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Prebiotic BGOS feeding is anxiolytic less anxious
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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[BD
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0
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150
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Anxiolytic changes coincided with
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Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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0.0
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.... a reduction in inflammatory cytokines
Yakult seminar “Gut – brain – microbiota” – Almere – 13-Oct-2016 © Beneficial Microbes Consultancy
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Human trials
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Human trials (1)
in order of publication date
• 124 healthy volunteers; mean age 61.8 years
• Double-blind, placebo (milk) controlled study
• Lactobacillus casei Shirota in milk-drink for 3
weeks
• Mood and cognition were measured at baseline,
and after 10 and 20 days of consumption.
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Human trials (1); LcS
POMS = profile of mood state
• An unexpected finding was that
the consumption of probiotics
resulted in a slightly-poorer
performance on two measures
of memory.
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• 31 chronic fatigue syndrome patients
• RDBPC study
• Lactobacillus casei Shirota in sachet-format for 8
weeks
• Beck Depression Inventory (BDI) and the Beck
Anxiety Inventory (BAI) at baseline and after 8 w.
Human trials (2)
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Human trials (2); LcS
• there was a significant improvement in anxiety among those taking the
active LcS compared to the placebo. The differences as assessed by the
BDI did not reach statistical significance.
BDI: a 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for
measuring the severity of depression
BAI: is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety in
children and adults
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• 55 volunteers with a score of ≤12 in the HADS-
anxiety subscale and in the HADS-depression
subscale and ≤ 20 in the HADS total score on initial
examination
• RDBPC study
• L.helveticus R0052 + B. longum R0175 in a stick
format, or placebo (xylitol, maltodextrin, plum
flavour and malic acid) for 30 days
• Tests: HSCL-90; HADS; PSS, CCL
• Urinary cortisol
Human trials (3)
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Human trials (3); L.h R0052 / B.l R0175
Hopkins Symptom Checklist-90.The HSCL-90 is a 90-item self-reported
multidimensional questionnaire screening a broad range of psychopathological
disorders
Hospital Anxiety and Depression Scale: The HADS, is a 14-item self-assessment
instrument, often applied and convenient for measuring psychological distress in
subjects with somatic or psychosomatic disorders
Perceived Stress Scale: The PSS is a 14-item self-reported questionnaire
assessing the degree to which recent life situations are appraised as stressful
Coping Checklist: The CCL is a validated 29-item questionnaire measuring five
types of coping strategies when confronting an adverse event: ‘problem solving’;
‘avoidance with wishful thinking’; ‘seeks social support’; ‘positive re-evaluation’;
‘self-blamed’.
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Human trials (3); L.h R0052 / B.l R0175
Probiotics-treated subjects had a lower global severity index of the HSCL-90 over
time, due to lower values for somatisation, depression and anger–hostility.
The potential usefulness of the probiotics as an anti-stress/anti-anxiety agent was
supported by diminished HADS global scores over time.
Taken together, probiotics appears to show a beneficial effect on general signs of
anxiety and depression, but this did not generalise to the PSS, although all three
tests comprise self-reported measures.
In the CCL test the two groups differed in emotional reactivity, with subjects
administered probiotics reducing their self-blame score.
L. helveticus R0052 and B. longum R0175 taken in combination display
beneficial psychological effects in healthy human volunteers
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• Same study as the previous one, but now in a
subpopulation of 25 subjects with urinary free
cortisol (UFC) levels less than 50 ng/ml at baseline
• More scores were beneficially affected by the
probiotics in this subpopulation
Human trials (3a)
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• 36 healthy women, age 30 y +/- 10.4
• RDBPC study
• B. animalis subsp lactis DN-173 010, Streptococcus
thermophilus CNCM I-1630, 2 strains of L. bulgaricus,
CNCM I-1632 and CNCM I-1519 and Lactococcus lactis
subsp lactis CNCM I-1631 fermented milk, non-
fermented milk or no intervention for 4 weeks
• functional magnetic resonance imaging before and after
the intervention to measure brain response to an
emotional faces attention task and resting brain activity.
Human trials (4)
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Human trials (4)
A fermented milk product with probiotic resulted in robust alterations in the
response of a widely distributed brain network to a validated task probing
attention to negative context, which have been associated with the dampening
of emotional and sensory responsiveness.
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• 44 university students who performed strenuous
exercise daily
• RDBPC study
• Lactobacillus gasseri OLL2809, OLL2809 + α-
lactalbumin, or placebo for 4 weeks
• Profile of Mood States (POMS) questionnaire
Human trials (5)
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Human trials (5)
LG2809 ingestion was effective in elevating mood from a depressed state.
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• 224 healthy volunteers
• RDBPC study
• yogurt containing L. gasseri SBT2055 and B.
longum SBT2928, or control yoghurt for 12 weeks
• levels of two stress-induced hormones,
adrenocorticotrophic hormone (ACTH) and cortisol
Human trials (6)
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Human trials (6)
These results suggest that the probiotic-containing test yogurt confers
health benefits by alleviating stress.
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• 50 healthy participants, mean age 23.22 years
• RDBPC study
• two strains of L. acidophilus CUL60 and CUL21,
B.lactis CUL34 and B.bifidum CUL20 in a capsule, or
placebo for 6 weeks
• anxiety levels decreased in the probiotic condition
whilst increasing in the placebo condition (p=0.042).
• ‘continuity of attention’ increased in response to the
probiotic treatment and decreased with the placebo
• group (p=0.035)
Human trials (7)
Abstract
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• 75 infants
• RDBPC study
• L. rhamnosus GG or placebo during the first 6 months
of life
• attention deficit hyperactivity disorder (ADHD) and
Asperger syndrome (AS)
• At the age of 13 y, ADHD or AS was diagnosed in 6/35
(17.1%) children in the placebo and none in the
probiotic group (P = 0.008).
Human trials (8)
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• 40 healthy participants without current mood disorder
• RTBPC study
• a multispecies probiotic containing B. bifidum W23,
B.lactis W52, L.acidophilus W37, L.brevis W63,
L.casei W56, L.salivarius W24, and 2 strains of
Lactococcus lactis W19 and W58 in a sachet, or
placebo
• cognitive reactivity to sad mood was assessed using
the revised Leiden index of depression sensitivity
scale
Human trials (9)
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Human trials (9)
The LEIDS-r is a self-reported
questionnaire with 34 items that
assesses to what extent
dysfunctional thoughts are
activated when experiencing mild
dysphoria
(i.e., it measures cognitive
reactivity to sad mood, also
referred to as vulnerability to
depression).
Rumination is the compulsively focused attention on the
symptoms of one's distress, and on its possible causes
and consequences, as opposed to its solutions.
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• 30 patients with laryngeal cancer
• RDBPC study
• Unknown strain of Clostridium butyricum for 2
weeks, twice a day in a capsule, or placebo
• Serum corticotropin-releasing factor
• The degree of anxiety assessed by the Hamilton
Anxiety Scale (HAMA)
Human trials (10)
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Human trials (10) m
Probiotics can ameliorate the clinical anxiety and biochemical features
of stress in patients scheduled for laryngectomy (and other surgery?)
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• 45 healthy medical students under academic
examination stress
• RDBPC study
• L.casei Shirota fermented milk, or placebo for 8
weeks prior to taking national exam
• Subjective anxiety scores
• Salivary cortisol levels
• The presence of physical symptoms
Human trials (11)
[Epub ahead of print]
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Human trials (11)
LcS may prevent hypersecretion of cortisol and physical symptoms (not shown
in this presentation) under stressful conditions, possibly through vagal afferent
signaling to the brain and reduced stress reactivity in the brain (the latter based
on a parallel rat study)
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• 45 healthy volunteers with no history of psychiatric
disorders
• Double-blind, placebo (maltodextrin) controlled
study
• FOS, Bimuno®-galacto-oligosaccharides, or
maltodextrin, daily for 3 weeks
• Awakening salivary cortisol measured on day 0 and
day 21
• Emotional test battery on day 21
Human trials (12); prebiotic
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Dot-probe task:
Attention to positive
stimuli is increased
BGOS reduces awakening cortisol and increases attention to positive
stimuli in healthy volunteers
Human trials (12); prebiotic
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Other things that could not be covered in this presentation
The gut microbiota produces other neuromodulatory molecules, such as
serotonin, GABA, melatonin
The gut microbiota is involved in brain development and cognition
The gut microbiota affects the blood brain barrier
Since pro- & prebiotics modulate the gut microbiota composition and
activity, they may also be involved in happiness, trustworthiness,
depression, sleeping, etc. … **
… in addition to anxiety, stress and autism
There is still room for mouse-models to study these gut microbiota-brain
interactions
** time for an anekdote?
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Wrap up and Take home messages
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Conclusions Part 2
• The gut microbiota is involved in brain functioning
• Pro-, pre- (and synbiotics) modulate the gut microbiota and
thereby can influence brain functioning as well
• Although mostly evidenced in animal studies, some clinical trials
show very promising results
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Script van deel 3 van de presentatie
hoe werkt dat nou?
wat kan ik er mee in de praktijk
take home messages deel 3
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Bepalen onze bacteriën in de darm wat we
in de supermarkt uit de schappen halen?
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Hoe werken probiotica? Hoe kunnen op het brein inwerken als ze in de darm zitten?
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bi-directional
crosstalk 100 trillion bacteria
60-70% of immune cells
100 billion neuronal cells
communication from gut to brain
communication from brain to gut
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1. Stress
a) barrier
b) transit
c) microbiota
2. Food intake
a) satiety
b) mood
3. Immunomodulation
a) cytokines via blood
4. Metabolite production
a) SCFA, GABA, 5-HT, etc
b) via blood, immune cells, ENS
5. Interaction with ENS
a) via vagus nerve
b) via blood
1 2 3 4 5
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Potential effects of pro- and prebiotics also, e.g., obesity, allergy, infection
also, e.g, inflammation
also, e.g., obesity, allergy, inflammation
but also, role in prevention of weight gain
also, e.g., kidney failure
e.g., IBS
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Saccharolytic and proteolytic activity
• Saccharolysis leads primarily to SCFA and gasses
• SCFA: acetate, propionate, butyrate
• lactate -> only accumulates when there
is a fast fermentation
• CO2, CH4, H2
• Proteolysis in addition leads to toxic metabolites
• BCFA: iso-butyrate, iso-valerate
• ammonia
• phenolics: phenol, indol, p-cresol, skatol
• H2S, CH3SH, etc
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Colonic metabolites some examples
• Butyrate:
• 70% of the fuel of colonocytes
• lack -> epithelial atrophy
• reduces cancer promotion in transformed tissue
• possibly reverses transformation by induction of
differentiation
• H2S, CH3SH:
• block butyrate oxidation
• ammonia:
• liver cirrhosis
• etc.
113 Experimental Biology 2012, San Diego, CA, USA -- April 23 -- © TNO
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Prolonged carbohydrate fermentation
proximal colon: primarily saccharolytic
fermentation
transverse colon: combination of saccharolytic
and proteolytic fermentation
distal colon: primarily proteolytic fermentation
distal colon: colon cancer and IBD
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microbiota host
Host – microbe interaction :
relevance for brain health
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Figure 1. Interactions between diet, the host and gut microbiome at the metabolite level.
diet fermentation by
gut microbiota
microbial
metabolites
tissue and organ
metabolism
host physiological
response
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Dieet-adviezen?
Afhankelijk van achterliggend probleem
overgewicht/obesitas
prikkelbare darm
coeliakie
darmontsteking
allergie
In bijna alle gevallen (behalve autisme)
vezels (groeibron voor microbiota -> SCFA, etc.)
Probiotica
diarree, constipatie
ontstekingsproblemen (huid, luchtwegen, darm)
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Dieet-adviezen? (2)
Ouderen
goed verteerbaar eiwit
vitaminen
vezels
Brein
mood/humeur -> tryptofaan (aminozuur in eiwit)
memory/geheugen -> probiotica?
ontwikkeling -> PUFAs
Stress (allerlei mogelijke vormen) -> verstoorde darm barriere
probiotica
glucose/glutamine
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Wrap up and Take home messages
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Conclusions Part 3
• Pro- en prebiotica kunnen op veel verschillende manieren de
darm-brein interactie moduleren.
• Effecten zijn stam-specifiek
• Dieet-advies sterk afhankelijk van achterliggende probleem
• For more information:
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Acknowledgements
• Henrike Hamer
• Steven Vanhoutvin
• Freddy Troost
• Daisy Jonkers
• Robert-Jan Brummer
• Tao He
• Roel Vonk
April 20, 2011 TIFN Satiety
screenings
study
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Dank u hartelijk voor uw aandacht!