De hersen-darm-as: de huidige stand van zaken volgens de wetenschap
Door: Judith Verbaan, februari 2019


Het is duidelijk dat er een directe relatie is tussen de hersenen en de darmen. Zo kan stress bijvoorbeeld leiden tot darmklachten, of krijgen we ‘een knoop in onze maag’ wanneer we iets heel spannend vinden. De hersenen beïnvloeden ons maagdarmstelsel. Maar dit is geen eenrichtingsverkeer, de connectie bestaat ook andersom. Onze darmfunctie kan een belangrijke invloed hebben op onze hersenfunctie, en daarmee mogelijk een belangrijke rol spelen bij stress, depressie, angststoornissen, autistische stoornissen en ADHD. Deze onderlinge connectie tussen onze hersenen en darmen wordt wel de hersen-darm-as (of in het Engels: brain-gut-axis) genoemd. Maar hoe werkt dat dan? Op welke manier kunnen onze darmen onze hersenen beïnvloeden? En in hoeverre kunnen wij onze darmen beïnvloeden met ons voedingspatroon, en daarmee mogelijk onze mentale gezondheid?


Ik bezocht op 16 januari de lezing ‘The Science of Gut Feelings’, onderdeel van ‘Mind Mood Microbes’: de tweede internationale conferentie over microbiota en de hersen-darm-as. Hier deelde een panel van deskundigen op het gebied van neurowetenschappen, psychologie en voeding de nieuwste inzichten op dit gebied volgens de wetenschap.


Microbioom: de minuscule beestjes die in onze darmen wonen
Tijdens de lezing werd uitgelegd dat de werking van de hersen-darm-as alles te maken heeft met de bacteriën die in onze darmen leven: ons darmmicrobioom, beter bekend als onze darmflora. Ons microbioom bestaat uit een enorme hoeveelheid microbiotische cellen: zo’n 10-100 x 1018. Dit zijn met name bacteriën in onze darmen, die er zijn in vele verschillende soorten die elk hun eigen genen bevatten. (10) Ter vergelijking: het totaal aantal menselijke cellen in ons lichaam is geschat op zo’n 3,72 x 1013. (2) We kunnen ons dus afvragen, als ons lichaam inderdaad meer microbiotische cellen dan menselijke cellen bevat, in hoeverre zijn wij dan mens? En worden wij dan elke keer dat wij poepen een klein beetje meer mens? Food for thought


Signalen via het bloed
Goed, het is dus duidelijk dat er een aanzienlijke hoeveelheid kleine beestjes in onze darmen woont. Deze bacteriën kunnen eiwitten produceren die vanuit de darmen naar het bloed kunnen worden getransporteerd en zo onder andere ons metabolisme en immuunsysteem kunnen beïnvloeden. Dit was al bekend. Wat nieuw is, is dat deze eiwitten ook de bloed-hersenbarrière kunnen passeren en zo de ontwikkeling van het brein – en dus mogelijk ook ons gedrag – kunnen beïnvloeden. (1) Om die reden worden onze darmen ook wel ons tweede brein genoemd.


Signalen via het zenuwstelsel
Onze hersenen en darmen staan dus met elkaar in verbinding via het bloed. Daarnaast is er een snelle connectie die verloopt via de Nervus Vagus, ook wel de zwerfzenuw genoemd. Darmbacteriën maken vele stofjes aan, waaronder stofjes die het humeur kunnen beïnvloeden. Denk hierbij aan serotonine en dopamine. De zenuwuiteinden van de Nervus Vagus kunnen deze stofjes opmerken en deze informatie vanuit de darmen naar het centrale zenuwstelsel sturen, dat hier vervolgens op kan reageren. (3)


Er wordt verondersteld dat de eerste twee levensjaren, waarin de meeste hersen –en microbioom ontwikkeling plaatsvindt, kritiek zijn voor de opbouw van belangrijke neuronale verbindingen. (7)(4) Er wordt momenteel aan gewerkt om de precieze werking van deze mechanismen op te helderen. Zo vertelde professor Rochellys Diaz Heijtz over het onderzoek wat zij uitvoert bij bacterievrije muizen. Deze muizen liet ze opgroeien in een steriele omgeving, om uit te zoeken of ze afwijkend gedrag zouden vertonen. En wat bleek? De muizen lieten hyperactiviteit en abnormaal sociaal gedrag zien, evenals een afwijkend serotoninegehalte. De bacterievrije muizen werden vervolgens in een omgeving met bacteriën gebracht, waar hun gedrag weer normaliseerde. Dit effect was het grootst bij jonge muizen. Bij oudere muizen was minder effect te zien na herintroductie van bacteriën. (8) Het is de vraag in hoeverre deze onderzoeken, uitgevoerd bij proefdieren, ook van toepassing zijn op mensen. Het lijkt erop dat veel neurale aandoeningen zoals Dyslexie, ADHD, Gilles de La Tourette en autisme verband houden met een afwijkend microbioom. Zo benoemde Heijtz dat 70% van de kinderen met een autistische aandoening ook last heeft van maag-darmproblemen. Het onderzoek op dit gebied zit echter nog in een te vroeg stadium om hier zekerheid over te kunnen geven. Lastig is hierbij bovendien het feit dat mensen zich niet zo makkelijk gedurende lange tijd in een bacterievrij kooitje laten opsluiten


Depressie
Er is een sterke toename van bewijs dat aangeeft dat afname van de darmflora of een disbalans in de darmbacteriën een rol zou kunnen spelen bij het ontstaan van depressie. Darmbacteriën produceren moleculen zoals dopamine, serotonine en gamma-aminoboterzuur (GABA) die onze hersenen kunnen beïnvloeden, en daarmee ons gedrag. Daaruit volgt dat als het microbioom een rol kan spelen bij het moduleren van ons gedrag, inname van de juiste micro-organismen met onze voeding wellicht een positief effect zou kunnen hebben op ons gedrag. Pre –en probiotica worden om deze reden door wetenschappers ook wel ‘psychobiotica’ genoemd. (5)(9)


Onderzoekers zijn bezig uit te zoeken of er een potentieel effect is van het gebruik van pro –en prebiotica op de mentale gezondheid, doordat het de reactie op stress verandert en symptomen van angststoornissen en depressie vermindert. Zo heeft de bacterie Lactobacillus rhamnosus bijvoorbeeld een sterk angst-remmend effect bij dieren. Dit werkt doordat de bacterie zelf GABA aanmaakt én de expressie van GABA receptoren verandert. Een combinatie van inname van verschillende bacteriën lijkt effectiever dan inname van één soort. (5) Wellicht kunnen in de toekomst psychobiotica worden gebruikt als onderdeel van de behandeling bij psychologische problemen. De onderzoeken zijn nu echter nog in beginstadia en probiotica moeten absoluut niet gebruikt worden als vervangers van antidepressiva.


De rol van voeding
Gezond, gevarieerd voedingspatroon
Als je een gezonde, gevarieerde darmflora wilt dan is het belangrijk om ook een gezonde, gevarieerde voeding te eten. Hierbij is het goed om veel te variëren met verschillende plantaardige producten, die vanwege hun hoge vezelgehalte een gunstig effect hebben op de darmfunctie.

Mediterraan dieet
Een ongezond voedingspatroon wat bijvoorbeeld hoog is in geraffineerde, bewerkte producten, suiker en transvetten kan ons microbioom aantasten en op die manier leiden tot psychologische problemen. Er is een aantal recente studies dat suggereert dat het Mediterrane dieet sommige symptomen van depressie zou kunnen verlichten. Dit is mogelijk toe te schrijven aan bepaalde componenten in het dieet, zoals veel onverzadigde vetzuren, vezels en probiotica en het type eiwitbron. (6)


Pro –en prebiotica
Hoewel er mogelijk een effect is van pre –en probiotica op de mentale gezondheid, moet dit nog wel met een gezonde kritische blik worden beschouwd. De meeste probiotica hebben geen psychobiotische activiteit. Er is slechts een klein percentage geteste bacteriën dat positieve neurologische effecten heeft. Bovendien overleven sommige bacteriën de opslag in winkels niet, of worden ze uitgeschakeld door de zure inhoud van de maag. En zelfs als de bacteriën in probiotica deze barrières overwinnen, dan is het nog niet bewezen dat ze ook daadwerkelijk een gezondheidsvoordeel opleveren. (5) Als je kiest voor voeding die probiotica bevat, kies dan voor gefermenteerde voeding zoals zuurkool, yoghurt, tempé, kefir, miso of kimchi. Kies in geval van yoghurt wel de varianten zonder toegevoegde suikers. Bij yoghurt die vol zit met suiker zijn de bacteriën namelijk al dood voordat ze in je darmen aankomen. Ook is het van belang om te kijken naar het aantal en soort bacteriën. Ideaal is een zo groot mogelijk aantal en variatie.


Conclusie
Onze darmen en hersenen staan sterk met elkaar in verbinding en beïnvloeden elkaar onderling via de zogenaamde hersen-darm-as. Deze connectie verloopt via door bacteriën geproduceerde eiwitten die door de bloed-hersenbarrière heen kunnen, en via het centraal zenuwstelsel (specifieker: de Nervus Vagus). De stofjes die door onze gigantische hoeveelheid darmmicroben worden geproduceerd kunnen de hersenfunctie en daarmee ons gedrag beïnvloeden. Bij onderzoeken met bacterievrije muizen is dit al gebleken, maar naar het precieze werkingsmechanisme hierachter bij mensen dient nog nader onderzoek plaats te vinden. De wetenschap op het gebied van de hersen-darm-as is de laatste jaren sterk in ontwikkeling, maar er is nog veel wat we niet weten. Wat we wel weten is dát er een connectie is en hoe deze ongeveer verloopt. Ook zijn er aanwijzingen dat er een positief effect is van psychobiotica op de darmflora en daarmee op bepaalde aandoeningen zoals depressie. Hier kan echter nog niet met zekerheid een uitspraak over worden gedaan. Tot we meer weten is het (wellicht weinig bevredigende) antwoord op de vraag welk voedingspatroon het meest geschikt is als volgt: een gezonde, gevarieerde voeding. Dit houdt een voeding in die onder andere laag is in toegevoegde suikers, geraffineerde producten en transvetten, en hoog in met name onverzadigde vetten, plantaardige voedingsmiddelen en vezels. Indien probiotica worden gebruikt, kies dan voor een zo groot mogelijke variatie aan bacteriën en haal dit bij voorkeur uit producten die deel uitmaken van een gezond voedingspatroon. Daarbij kan bijvoorbeeld gedacht worden aan tempé of yoghurt zonder toegevoegde suikers.


Ik wil dit artikel graag afsluiten met een uitspraak die professor John Cryan aan het eind van zijn lezing deed. John citeerde Hippocrates’ ‘Let food be thy medicine’ en kwam met alle nieuwe inzichten op het gebied van de hersen-darm-as tot de volgende variant op deze uitspraak: ‘Let food for your microbes be the medicine for your mind’. Met andere woorden: eet een gezonde, gevarieerde voeding waar je darmbeestjes blij van worden, dat vindt je brein ook fijn.

Verwijzingen

  1. Arentsen, T., Qian, Y., Gkotzis, S., Femenia, T., Wang , T., Udekwu, K., . . . Diaz Heijtz, R. (2017). The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior. Molecular Psychiatry, 257-266.
  2. Bianconi, E., Piovesan, A., Facchin, F., Beraudi, A., Casadei, R., Frabetti, F., . . . Canaider, S. (2013). An estimation of the number of cells in the human body. Annals of Human Biology, 463-471.
  3. Bonaz, B., Bazin, T., & Pellissier, S. (2018). The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Frontiers in Neuroscience, 1-9.
  4. Codagnone, M. G., Spichak, S., O’Mahony, S. M., O’Leary, O. F., Clarke, G., Stanton, C., . . . Cryan, J. F. (2019). Programming Bugs: Microbiota and the Developmental Origins of Brain Health and Disease. Biological Psychiatry, 150-163.
  5. Cryan, J., & Dinan, T. (2014). Psychobiotics: How gut bacteria mess with your mind. The Big Idea. Opgehaald van https://www.newscientist.com/article/mg22129530-400-psychobiotics-how-gut-bacteria-mess-with-your-mind/
  6. Dinan, T. G., Stanton, C., Long-Smith, C., Kennedy, P., Cryan, J. F., Cowan, C. S., . . . Sanz, Y. (2018). Feeding melancholic microbes: MyNewGut recommendations on diet and mood. Clinical Nutrition, 1-7.
  7. Heijtz, R. D. (2016). Fetal, neonatal, and infant microbiome: Perturbations and subsequent effects on brain development and behavior. Seminars in Fetal and Neonatal Medicine, 410-417.
  8. Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., . . . Pettersson, S. (2011). Normal gut microbiota modulates brain development and behavior. Proceedings of the National Academy of Sciences of the United States of America, 3047-3052.
  9. Steenbergen, L., Sellaro, R., van Hemert, S., Bosch, J. A., & Calzato, L. S. (2015). A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain, behaviour, and imunity., 258-264.
  10. Turnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C., Knight, R., & Gordon, J. I. (2007). The human microbiome project: exploring the microbial part of ourselves in a changing world. Nature, 804-810.

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