Voeding en het darmmicrobioom -

wat weten we nu eigenlijk?Tim de Meij kinderarts-MDL

23-1-2020

(potentiële) belangenverstrengeling Zie hieronder

Voor bijeenkomst mogelijk relevante relaties met bedrijven Nutricia Nederland BV

• Sponsoring of onderzoeksgeld• Honorarium of andere (financiële)

vergoeding• Aandeelhouder• Andere relatie, namelijk …

• nvt• Sprekersvergoeding voor dit congres

• nvt• Lid van de Medische Adviesraad

Disclosure belangen spreker

Tim de Meij

Bach, NEJM 2002

PresentatorPresentatienotitiesAfgelopen decennia afname infectieziekten maar gelijktijdig verontrustende toename auto-immuunziektenMogelijke oorzaken: dieet, medicatie (gezien korte termijn moet het iets anders zijn dan genetische oorzaak)Shared pathomechanism

Ridaura, Science 2013

Manipulatie van het microbioom en ziekte

PresentatorPresentatienotitiesDeze studie bevestigt dat manipulatie van het microbioom daadwerkelijk klinische effecten heeft, causale rol microbioom bij bijvoorbeeld obesitas hiermee bevestigt, maar zelfde geldt voor bijvoorbeeld IBD en infecties zoals Clostridium infecties

http://www.google.nl/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjP7N7ZhtfXAhVJFOwKHTBqCscQjRwIBw&url=http://www.theisthmus.com.au/2016/05/the-power-of-the-gut-outside-of-the-gut/&psig=AOvVaw1sUydoHJOFPOuJgh9lGUeS&ust=1511607443088995

Rook, UCL 2019

Microbioom en obesitas

Wang et al, 2011 NatureKoeth et al, 2013 Nature Medicine

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Microbioom en ziekte: ook invloed buiten de darm

PresentatorPresentatienotitieshttps://www.sciencedirect.com/science/article/pii/B9780124078253000022

NRC, 16 jan 2019

Slaan we door?

Bubble child

Ideeën over microbioom, kolonisatie en manipulatie veranderen

• ‘Sterile womb’ and ’in utero colonization’• Pancreas is sterile, also in pancreatic cancer

Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life FactorsMoossavi et al, Cell host & Microbe. 2019

Clarke et al, Pharmacological Reviews 2019

Arrieta. Front Immunol 2014

PresentatorPresentatienotitiesMost abundant bacterial families are depicted in circles, where the size of the circle is proportional to the relative abundance of the bacterial taxa at each growth stage. The intestinal microbiota of the newborn is initially colonized by Enterobacteria. In the days after, strict anaerobic bacteria dominate the microbial community. During the first month, bifidobacterial species predominate in the gut, but the introduction of solid foods at around 4–6 months is accompanied by an expansion of clostridial species (Lachnospiracea, Clostridiaceae, and Ruminococcaceae). Members of the Ruminococcaceae family continue to increase in abundance in the following months. By 2–3 years of age, the microbiota composition consists of mainly Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae, which then remains stable into adulthood.

Diversiteit in en om ons heen

Mensen, dieren, planten en omgeving: uitwisseling microbiota

Flandroy, Science of The Total Environment, 2018

Omgeving ziekenhuizen en pathogenen

Rose et al., Am J Infect Contr 2014

En als je met de bus komt…

Conceicao PlosOne 2014; Lutz Am J Infect Contr 2014; Afshinnekoo Cell Systems 2015

Relatie lagere biodiversiteit- humane microbioom – gezondheid?

Menard, FASEB 2014

Verontreiniging voeding en invloed microbioom

Romanelli WHO 2017, Mahy, WHO 2017

Bioversity int 2017

Von Hertzen EMBO 2011

Different food components drive changes in the gut microbiota

reciprocal interactions between diet, gut microbiota and host

Food components may influence and determine human health

PresentatorPresentatienotitieshttps://pdf.sciencedirectassets.com/271165/1-s2.0-S0963996918X00106/1-s2.0-S0963996918305829/main.pdf?X-Amz-Date=20200117T135039Z&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Signature=14f3655ebba94ee01f12bfeb7daf13e6dfb991cce590389c7f2444e836b4d1a4&X-Amz-Credential=ASIAQ3PHCVTYQWCPI5WN%2F20200117%2Fus-east-1%2Fs3%2Faws4_request&type=client&tid=prr-6b08c912-2c7d-400c-9c66-e143c479ba0e&sid=2bddb28a5983d14b660b5c273c666d7f584bgxrqb&pii=S0963996918305829&X-Amz-SignedHeaders=host&X-Amz-Security-Token=IQoJb3JpZ2luX2VjEB4aCXVzLWVhc3QtMSJHMEUCIEJdeNXn%2B8KZOjxXNwAad6a1UmH0igwc8GtwCHVVw4PUAiEA5ZWQ0S0hRCZSx2mLcYbYkQevkVhFV0TLOJ47zqgJRXEqvQMIpv%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FARACGgwwNTkwMDM1NDY4NjUiDM1j3kRUo3ZFmpL%2F9CqRA4Z%2BZdWsezpuLmtdWraZ7eBEE63S2NW92fd25lxrcKNeWyY5RBOJ6SCRofOuzQZVzYayUArNsJJ8FBdlR9k5j3XLj33zjhCAwR5tyZ8Jb7lfrtodEfsFJq3jufDQCrguoKUzIwqDSS06ivXQxQjyfn1zHXPue%2BNUReAmv1%2BOEzHhxkbPORG0l8EtyCQkRg05Pu9Ay59QjotMOrGCdbwivm6y2pfQZME09bb40D8YsvCZY91l%2BZCTFwH8Zah4%2BhI3vzzSghBiejNH%2FL5xPLEeWRWN28HdNPE6BpyGONyndQfR%2B%2BaSkrrfz2OBjW4NwNbP2mCkGQkITDEn3S4t5Nv5UoTgJz4%2B1MFA6yFfIYExW%2BhzisH5PzTLzBrgdx7Fyszyl3uhU%2FM7jY3kKRzbBoOfZ7TzCGe58vlj1898LigC3Cm6Yfb59j2buiMYruIKxh%2FbdrOQrpqEhqoCbp2tDo5Ll2F3ludP2XkR%2FQnBmakQpQAhsotmqoJoIjNXzhwYv2vo8rmOhlNZwOCsyG9%2FPcH4a6KzMLLohvEFOusBqD2aI%2FDQ675gViEn3AdAb%2BHXsnvn5%2FfTb16MJ9JEhdZogN33MgrvnB49W0kHFXMdAcgPyjGPbNDfv3Yb93xe9SX9JHzvFCztv6ZjUFf%2FmdJEJz%2FbSlA%2Bz4D8TJUvFXl3eOJsGV7OugUxT8bCvrzUD1BY25KoXFyuEAyQevOC2hMvQeT3Txika7NwzWVe8Sb3%2BrQoi9xIoEABWtlIjotWhPKssj0fusDjpIZkBrF832DaS11XK5a9W2f4KeutFC5aHH8UpZiDzsLK59UJ2yUrRWUQ3S0R6ykuMFwEYvSi37Ej3F5W5RQMvjXw0w%3D%3D&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&X-Amz-Expires=300&hash=c6c26a38a454760dc6bd643c7f2e6d70450c895bd5093405bdb580ac228b772e

Danneskiold et al. Food Res int 2019

PresentatorPresentatienotitiesOverview of the interplay between food components, gut microbiota, metabolites, and host health. Dietary compounds may elicit changes in thecomposition and the activity of the gut microbiota resulting in the generation of secondary metabolites that modulate host responses. Arrows indicate interactionbetween gut microbiota and metabolites. Ahr: Aryl: aryl hydrocarbon receptor; BCAAs: branched-chain amino acids; MAC: microbiota accessible carbohydrates;SCFAs: short-chain fatty acids; TMAO: trimethylamine oxide.

Vezels en microbioom

Am J Clin Nutr 2018

PresentatorPresentatienotitiesABSTRACTBackgroundDysfunction of the gut microbiota is frequently reported as a manifestation of chronic diseases, and therefore presents as a modifiable risk factor in their development. Diet is a major regulator of the gut microbiota, and certain types of dietary fiber may modify bacterial numbers and metabolism, including short-chain fatty acid (SCFA) generation.ObjectiveA systematic review and meta-analysis were undertaken to assess the effect of dietary fiber interventions on gut microbiota composition in healthy adults.DesignA systematic search was conducted across MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials using culture and/or molecular microbiological techniques evaluating the effect of fiber intervention on gut microbiota composition in healthy adults. Meta-analyses via a random-effects model were performed on alpha diversity, prespecified bacterial abundances including Bifidobacterium and Lactobacillus spp., and fecal SCFA concentrations comparing dietary fiber interventions with placebo/low-fiber comparators.ResultsA total of 64 studies involving 2099 participants were included. Dietary fiber intervention resulted in higher abundance of Bifidobacterium spp. (standardized mean difference (SMD): 0.64; 95% CI: 0.42, 0.86; P 

De Filippis et al, Gut 2016

153 individuals habitually following omnivore, vegetarian or vegan diets. The majority of vegan and vegetarian subjects and 30% of omnivore subjects had a high adherence to the MD.

We were able to stratify individuals according to both diet type and adherence to the MD on the basis of their dietary patterns and associated microbiota.

We detected significant associations between consumption of vegetable-based diets and increased levels of faecal short-chain fatty acids, Prevotella and some fibredegradingFirmicutes, whose role in human gut warrants further research.

Conversely, we detected higher urinary trimethylamine oxide levels in individuals with loweradherence to the MD

De Filippis et al, Gut 2016

De Filippis et al, Gut 2016

‘High-level consumption of plant foodstuffs consistent with a MD is associated with beneficial microbiome-related metabolomic profiles in subjects’

De Filippis et al, Gut 2016

PresentatorPresentatienotitiesSignificance of this studyWhat is already known on this subject?Diet can significantly impact the gut microbiota and metabolome.Negligible differences in gut microbiota and faecal short-chain fatty acids were previously reported between habitual omnivores and vegans.Mediterranean diet is a recognised healthy dietary pattern that has not previously been related to the composition of the gut microbiota and related metabolome.What are the new findings?Habitual vegetarian and vegan diets promote enrichment of fibre-degrading bacteria in the gut.Subjects who consume a Mediterranean diet rich in fruit, legumes and vegetables have higher levels of faecal short-chain fatty acids, regardless of the diet type.Low adherence to the Mediterranean diet corresponds to an increase in urinary trimethylamine oxide levels, a potential risk factor for cardiovascular disease.How might it impact on clinical practice in the foreseeable future?Microbiota modulation through consumption of diets rich in diverse vegetable foods offers the prospect of increasing health and mitigating disease risk.

De Filippis et al, Gut 2016

►Greater adherence to a Mediterranean dietis associated with a lower risk of later onsetCrohn’s disease.► In two large prospective cohorts in Sweden,poor adherence to a Mediterranean dietconferred a population attributable risk of 12%for later-onset Crohn’s disease

Voeding en microbioom

• 34 gezonde personen dagboek intake. • Dagelijks sampling ontlasting• Doel: Hoe beinvloedt dagelijkse voedinghet microbioom?

Johnson et al, Cell Host Microbe 2019

Daily Dietary Intake and Microbiome Composition Are HighlyVariable and Personalized

Daily microbiome variation is related to food choices, but notto conventional nutrients

Daily microbiome variation depends on at least two days ofdietary history

Similar foods have different effects on different people’smicrobiomes

Johnson et al, Cell Host Microbe 2019

Conclusies en aanbevelingen

• divers diet helps maintain a stable microbiome, while also giving your body all the nutrients it needs to stay healthy.

• the microbiome’s response to food varies between individuals tailored dietary advice (instead of a universal diet for everyone)

• personalized gut microbiome treatments that will improve not only gut wellbeing, but also overall health.

• nutritional advice should focus more on recommending people combine fruit and vegetables in their daily diet instead of prioritizing specific fibers

Johnson et al, Cell Host Microbe 2019

PresentatorPresentatienotitiesLet’s take a simple example of a green leafy vegetable such as spinach, which is rich in iron. In addition to iron, spinach contains a multitude of nutrients, such as fiber, minerals and carbohydrates. All of these elements—the whole—therefore strengthen spinach’s relationship with the microbiome and have an impact on gut microbiota composition

Hoe diverser, hoe stabieler

De Meij et al, FASEB 2016

Voedingsoplossingen om de darmmicrobiota en het immuunsysteem te beïnvloeden

Prebiotica zijn vezels die een voedingsbodem vormen voor gunstige bacteriën in de darmmicrobiota1

Probiotica zijn levendebacteriën die zich in de darmen kunnen vermeerderen en daar een positieve invloed hebben op de gezondheid2,3

Postbiotica onstaantijdens fermentatie door bacteriën en kunnen een positieve invloedhebben op de gezondheid4

Prebiotica Probiotica Postbiotica

1. Gibson et al. 2017 2. inns 2013 3. Hill et al. 2014 4. adapted from Patel RM & Denning PW Clin Perinatol 2013;40:11-25

PresentatorPresentatienotities4. Patel RM & Denning PW (2013) Therapeutic use of prebiotics, probiotics, and postbiotics to prevent necrotizing enterocolitis: what is the current evidence?. Clin Perinatol 40:11-25

Pre-, pro- en synbiotica in zuigelingenvoeding

Shamir R et al. (2015) Essential Knowledge Briefing, Wiley, Chichester.

Synbiotica herstellen de verlate kolonisatie van

bifidobacteriën in de darmen bij kinderen

geboren via een keizersnede

Effect synbiotica (GOS/lcFOS 9:1 en Bifidus Breve ) op bifidobacteriën in de darm

Chua MC et al., 2017 Jul;65(1):102-106

PresentatorPresentatienotitiesSyneo is gunstig voor de opbouw van het darmmicrobioomHet toevoegen van de synbiotische mix Syneo aan flesvoeding heeft een gunstig effect op het darmmicrobioom . Het aandeel van gunstige bifidobacteriën neemt toe en het aandeel ongunstige Clostridium-bacteriën neemt af, zo blijkt uit een gerandomiseerde gecontroleerde studie (RCT) onder 102 gezonde baby’s (Abrahamse-Berkeveld 2016). Hierdoor lijkt het darmmicrobioom meer op dat van borstgevoede baby’s. Ook bij peuters zijn gunstige effecten van de synbiotische mix gevonden: het aantal bifodobacteriën nam toe, de pH in de darmen nam af en de ontlasting werd zachter (Kosuwon 2018). Ander onderzoek laat zien dat Syneo gunstige effecten heeft na een keizersnede. Kinderen die via een keizersnede geboren worden, kunnen net zo snel als vaginaal geboren kinderen een bifidogeen darmmicrobioom opbouwen, als ze flesvoeding met Syneo krijgen . Dit blijkt uit een onderzoek onder 153 zuigelingen die via een keizersnede geboren zijn (Chua 2017). JULIUS Study()

Levine A, Sigall Boneh R, Wine E. GUT 2017

DIET AFFECTS BOTH HOST AND MICROBIOME

Mucous LayerGoblet Cells

TregsCathelicidinsDefensins

IntracellularBacterial Clearance

Intestinal Permeability

• Maltodextrins• Emulsifiers• Low Fiber• High Fat/High

sugar

• Emulsifiers• Maltodextrins• High Fat (bile

acids)

• Low Fiber• Low Resistant

Starch• High Fat• High Animal

ProteinDysbiosis

PathobiontsMetabolome

Mucosal Adhesion Translocation

Virulence Pathogenicity

• Emulsifiers• Carrageenans• Gluten• High Fat diet• Alcohol

• High Fat High Sugar Diet

• Emulsifiers• Low Fiber

• Low Fiber• High Fat• Gluten

• High Fat diet• Maltodextrins

• High Fat High Sugar Diet

• High Fat diet • Gluten• Emulsifiers• Taurine• Low Fiber

Dysbiosis involves increased Proteobacteria and decreased Firmicutes

Slide courtesy of Professor Arie Levine

PresentatorPresentatienotitiesThe appropriate way to view the effect of diet is by analyzing the effect of dietary components on host or microbiome, each divided in this slide in to 4 different aspects of pathogenesis . On the left we have host factors such as barrier function and innate immunity, on the right factors affecting the microbiota. High fat-high sugar diet and low fiber diet as well as emulsifiers affect the intestinal mucous layer and goblet cells. Low fiber and high fat diet along with gluten affect the regulatory T cells, cathelicidins and defensins. High fat diet, emulsifiers, carrageenans, gluten and alcohol affect the intestinal permeability. High fat diet and maltodextrins affect the intracellular bacterial clearance.

High fat-high sugar diet, high fat diet and low fiber diet as well as additives such as taurine, emulsifiers and gluten cause dysbiosis and affect the pathobionts. Low fiber diet, high fat diet as well as diets rich in animal protein and low resistant starch affect the metabolomes. High fat diet along with emulsifiers and maltodextrins increase the virulence in the gut as well as pathogenicity of the gut microbiomes. Low fiber and high fat-high sugar diet along with maltodextrins and emulsifiers increase mucosal adhesion and translocation across the mucosal layer.

Reference:Levine, Sigall Boneh, Wine. Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases. Gut. 2018;66:1-13.

Samenvattend

• Voeding grote invloed op samenstelling en functie microbioom• Microbioom valt te manipuleren door aanpassen voeding• Bewijs voor effect van gezonde voeding op gezondheid, met

microbioom als mediator• Voeding als therapie• Diversiteit belangrijke uitkomstmaat

Dianummer 1Disclosure belangen spreker�Tim de MeijDianummer 3Dianummer 4Dianummer 5Dianummer 6Dianummer 7Slaan we door?Dianummer 9Dianummer 10Ideeën over microbioom, kolonisatie en manipulatie veranderenDianummer 12Dianummer 13Dianummer 14Dianummer 15Dianummer 16Dianummer 17Dianummer 18Dianummer 19Dianummer 20Dianummer 21Dianummer 22Dianummer 23Dianummer 24Different food components drive changes in the gut microbiota

reciprocal interactions between diet, gut microbiota and host

Food components may influence and determine human health

Dianummer 26Vezels en microbioomDianummer 28Dianummer 29Dianummer 30Dianummer 31Dianummer 32Dianummer 33Voeding en microbioomDianummer 35Conclusies en aanbevelingenDianummer 37Voedingsoplossingen om de darmmicrobiota en het immuunsysteem te beïnvloedenDianummer 39Effect synbiotica (GOS/lcFOS 9:1 en Bifidus Breve ) �op bifidobacteriën in de darm �Dianummer 41DIET AFFECTS BOTH HOST AND MICROBIOMEDianummer 43Dianummer 44Dianummer 45Samenvattend