De rol van FODMAPs in bovenste gastro-intestinale effecten en signalisatie tussen het maagdarmstelsel en de hersenen
PRIKKELBARE DARMSYNDROOM: DE ROL VAN VOEDING
Krampen, opgeblazen gevoel, constipatie en/of diarree, urgente ontlasting: deze symptomen controleren het leven van patiënten met prikkelbare darm syndroom (PDS). De ontwikkeling van deze symptomen wordt in de hand gewerkt door overgevoeligheid aan een specifieke groep natuurlijk voorkomende koolhydraten, FODMAPs (fermenteerbare oligo-, di- en monosachariden en polyolen ) genaamd. Hiernaast spelen het centraal zenuwstelsel en een afwijkende respons van de maag op de inname van FODMAPs een rol in de pathofysiologie van PDS. Het beperken of vermijden van de inname van deze FODMAPs is bijgevolg een goede strategie voor PDS-patiënten om controle te krijgen over hun symptomen en de kwaliteit van hun leven te verbeteren.
PDS is een veelvoorkomende aandoening in de gastro-enterologie. Hoewel het onderzoek rond PDS de laatste jaren sterk is uitgebreid, is de exacte oorzaak ervan nog steeds niet volledig ontrafeld. Een van de factoren die een rol speelt in de pathofysiologie van PDS is voeding. In deze studie onderzochten we het effect van specifieke koolhydraten, FODMAPs, op de maagrespons bij vijftien gezonde personen en zes patiënten met PDS door hen verschillende FODMAP-oplossingen toe te dienen via een maagsonde. De gezonde vrijwilligers kregen op verschillende testdagen drie verschillende FODMAP-oplossingen, namelijk fructanen, fructose en een FODMAP mix, en glucose als controle-oplossing toegediend. De patiënten werden enkel blootgesteld aan fructanen en glucose op twee verschillende testdagen. Tijdens de gehele duur van het experiment, wat ongeveer vier uur per testdag in beslag nam, werd de druk in de maag gemeten met behulp van een manometrische sonde die via de neus tot in de maag werd opgeschoven. Aan de hand van deze maagdrukmeting kan de maagaccommodatie, d.i. de respons van de maag op de inname van voedsel, beoordeeld worden. In normale omstandigheden zet het bovenste deel van de maag uit wanneer voedsel wordt ingenomen, om zo een reservoir te vormen waarin het voedsel tijdelijk kan worden opgeslagen. Eerder onderzoek toonde aan dat een subgroep van patiënten met functionele maagdarmaandoeningen een afgenomen maagaccommodatie vertoont, wat kan leiden tot symptomen zoals vroegtijdige verzadiging en gewichtsverlies. In deze studie leidde de toediening van fructanen bij gezonde vrijwilligers tot een verminderde accommodatierespons vergeleken met de andere FODMAP-oplossingen en de controle-oplossing. Dit zou verklaard kunnen worden aan de hand van de concentratieverschillen tussen de oplossingen. Echter, in patiënten werd verrassend genoeg het tegengestelde waargenomen: fructanen gaven een sterkere maagaccommodatie in vergelijking met glucose. Verschillende hypotheses kunnen hier naar voor geschoven worden om deze resultaten te verklaren: een afwijkende activatie van mechanoreceptoren in de maagwand, die een belangrijke rol spelen in de initiatie van de maagaccommodatie, een veranderde vrijzetting van hormonen die de maagaccommodatie beïnvloeden of activatie van andere signaling pathways na binding van fructanen aan de zogenaamde “nutrient sensing”-receptoren. Het exacte mechanisme dat achter deze bevindingen schuilt, moet echter nog achterhaald worden in verder onderzoek.
In een tweede aspect van de studie werd de intensiteit van gastro-intestinale symptomen na FODMAP-inname onderzocht. Dit gebeurde aan de hand van een vragenlijst waarbij verschillende symptomen op vooraf bepaalde tijdstippen gescoord werden op een schaal van 100. Bij de gezonde vrijwilligers werd na FODMAP-infusie een lichte toename in een aantal symptomen vastgesteld, zoals voor winderigheid en krampen, maar deze verschillen waren niet significant. Wanneer de symptoomscores van de controlepopulatie vergeleken werden met deze van de patiëntenpopulatie, vonden we dat zowel de inname van glucose als van fructanen geassocieerd waren met significant hogere symptoomscores in de patiëntenpopulatie voor alle gemeten symptomen. Dit resultaat bewijst dat FODMAPs een rol spelen in de symptoomontwikkeling in PDS. De symptomen kunnen verklaard worden aan de hand van de eigenschappen van FODMAPs. Deze koolhydraten worden namelijk slecht of niet opgenomen in het maagdarmstelsel, waardoor ze gefermenteerd worden door darmbacteriën en er waterstof- en methaangassen ontstaan. Verder zorgen FODMAPs ervoor dat er water wordt aangetrokken naar de darmen. De verhoogde gasproductie en het toegenomen watergehalte in de darmen leiden zo tot luminale distensie, wat zich vertaalt in verschillende klachten zoals krampen, opgeblazen gevoel en winderigheid. Patiënten met PDS zijn vaak overgevoelig aan deze luminale distensie, wat leidt tot toegenomen symptoomscores in de patiëntenpopulatie. De toegenomen scores na infusie van de controle-oplossing kunnen verklaard worden aan de hand van het nocebo-effect, het tegengestelde van het placebo-effect. Hierbij beïnvloedt de negatieve mentale toestand van de patiënt de intensiteit en ernst van de symptomen die waargenomen worden. Deze resultaten maken duidelijk dat het centraal zenuwstelsel ook een rol speelt in PDS. Verder bewijs voor de link tussen PDS en het centraal zenuwstel wordt geleverd door de vaststelling dat PDS-patiënten naast hun maagdarmklachten vaak ook psychologische symptomen, zoals angst of depressie, vertonen.
Om de link tussen het maagdarmstelsel en het centraal zenuwstelsel verder te onderzoeken, testten we ten slotte ook de psychologische effecten van de inname van FODMAPs. Dit gebeurde opnieuw aan de hand van vragenlijsten waarbij de emotionele toestand en de gemoedstoestand van de proefpersonen gescoord werden. Voorbeelden van emoties die bestudeerd werden zijn vermoeidheid, kracht, boosheid en angst. In gezonde vrijwilligers bleven de psychologische effecten van de infusie van FODMAPs beperkt. In de patiëntenpopulatie werden echter toegenomen psychologische effecten waargenomen in vergelijking met de controlegroep, zowel voor fructanen als voor glucose. Zo scoorden de patiënten bijvoorbeeld hoger op spanning, neerslachtigheid en vermoeidheid, en lager op controlegevoel, kracht en blijheid. Deze resultaten ondersteunen enerzijds het nocebo-effect, en leveren anderzijds aanvullend bewijs dat het centraal zenuwstelsel betrokken is in de pathofysiologie van PDS.
Deze studie toont aan dat de inname van FODMAPs een rol speelt in de ontwikkeling van gastro-intestinale symptomen en leidt tot een afwijkende maagaccommodatie bij PBS. Een mogelijke strategie in het verlichten van de symptomen van PDS is dan ook het beperken of vermijden van deze FODMAPs in het dagelijks dieet. Hiernaast bewijst deze studie dat het centraal zenuwstelsel betrokken is in de pathofysiologie van PDS. Verder onderzoek is echter nodig om te achterhalen welke mechanismen betrokken zijn in de afwijkende maagrespons en welk effect FODMAPs precies hebben op de psychologische status van patiënten.
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