Hoe onze darmen kunnen helpen bij klachten na chemotherapie
In ons land krijgen gemiddeld 212 mensen per dag de diagnose van kanker. Ook mijn familie bleef niet van de ziekte gespaard. Hoewel steeds meer mensen kanker overleven, eindigen hun klachten niet altijd na de behandeling. Chemotherapie kan namelijk zeer ingrijpend zijn, ook nadat de kanker is overwonnen. Naast de bekende bijwerkingen zoals misselijkheid, haaruitval of vermoeidheid kan de behandeling ook leiden tot psychologische, sensorische, en cognitieve klachten. Uit mijn masterthesis blijkt dat een antwoord op die tweede soort klachten mogelijk in onze darmen ligt. Butyraat, een stof die door bacteriën in onze darmen wordt geproduceerd, lijkt sommige veranderingen in fysieke activiteit, angstgerelateerd gedrag, en pijnsensitiviteit te kunnen tegengaan. Dit bleek uit onderzoek bij muizen.
Wanneer de chemotherapiebehandeling stopt, doen de klachten dat niet altijd
Chemotherapie is wellicht een van de bekendste kankerbehandelingen. Ze doodt kankercellen of verhindert de verdere groei ervan. Chemotherapie tast echter ook gezonde cellen aan, wat leidt tot ongewenste bijwerkingen. Naast de bekende lichamelijke klachten ervaren sommige patiënten ook psychologische klachten zoals stress, angst, en depressieve symptomen; sensorische klachten zoals tintelingen, gevoelloosheid, en pijn; en cognitieve klachten zoals moeilijkheden met aandacht, concentratie, geheugen, leren, en redeneren. Deze bijwerkingen kunnen een enorme impact hebben op het leven en welzijn van een kankerpatiënt. De draad van het gewone leven terug oppikken wordt daardoor moeilijk. Daarom is het belangrijk om niet alleen te onderzoeken hoe we kanker kunnen behandelen, maar ook hoe we de gevolgen van die behandeling kunnen beperken.
Waarom het vaak start met muizenonderzoek
Om te beginnen is het niet zo eenvoudig om een grote homogene steekproef van chemotherapiepatiënten te verzamelen. Patiënten verschillen onderling namelijk sterk in behandelingsintensiteit, tumorplaats en type, en medische voorgeschiedenis. Daarom gebruiken veel onderzoekers muizen. In een muizenstudie kunnen onderzoekers deze factoren beter onder controle houden, doordat alle muizen binnen een bepaalde onderzoeksgroep dezelfde behandeling, interventie, en procedures krijgen. Zo is het makkelijker om te onderzoeken welke veranderingen samenhangen met het chemotherapieregime of de interventie. Als een interventie in zulke preklinische studies veelbelovend blijkt, kan ze later verder onderzocht worden bij mensen.
Een onverwachte bondgenoot: onze darmbacteriën
Wat hebben onze darmen met onze hersenen te maken? Meer dan je misschien zou denken.
Ons maag-darmstelsel is de thuisbasis voor een diverse groep micro-organismen, die we samen darmmicrobiota noemen. Deze bacteriën, virussen, en archaea zijn onmisbaar in de regeling van ons immuunsysteem en stofwisseling. Daarnaast vervullen ze een cruciale rol in de bidirectionele communicatie en interactie tussen onze hersenen en ons maag-darmstelsel. Via verschillende routes kunnen signalen in beide richtingen worden uitgewisseld: onze hersenen beïnvloeden onze darmen en omgekeerd beïnvloeden onze darmen hersenprocessen zoals gedrag, cognitie, en emotie.
Een voorbeeld van die signaalstoffen is korteketenvetzuren. Dat zijn stoffen die darmbacteriën produceren terwijl ze voedingsvezels fermenteren. Butyraat is een van de meest voorkomende korteketenvetzuren in onze darmen. Eerder onderzoek bij muizen toonde al dat butyraat positieve effecten kan hebben op cognitief en motorisch functioneren bij verschillende neurodegeneratieve aandoeningen. Dit alles samen bracht ons bij de vraag: kan butyraat ook helpen tegen de gevolgen van chemotherapie?
Zeven weken, vier groepen muizen, en een heleboel gedragstesten
Om deze vraag te beantwoorden, verdeelden we de muizen in vier groepen. Sommige kregen chemotherapie, andere niet, en binnen beide groepen kregen muizen ofwel butyraat ofwel een controle-interventie. Gedurende drie weken kregen de muizen enkel de interventie. Vervolgens combineerden we vier weken de interventie met de chemotherapie. Na die zeven weken onderzochten we hun gedrag met verschillende testen. We bestudeerden hun fysieke activiteit, verkennend gedrag, angstgerelateerd gedrag, leer- en geheugenfuncties, en pijngevoeligheid. Door de resultaten van de verschillende groepen met elkaar te vergelijken, konden we de gevolgen van chemotherapie onderzoeken en controleren of butyraat daar iets aan veranderde.
De effecten van butyraat
De gedragstesten toonden dat chemotherapie ook bij muizen grote gevolgen heeft. Ze verloren gewicht, werden minder actief, exploreerden minder, en vertoonden meer angstgerelateerd gedrag. Ook veranderde hun gevoeligheid voor pijnlijke prikkels: de muizen die chemotherapie kregen reageerden minder snel op deze prikkels, wat wijst op een lagere pijnsensitiviteit.
Sommige van die veranderingen waren minder groot bij muizen die naast chemotherapie ook butyraat kregen. Ze waren actiever dan de muizen die chemotherapie en de controle-interventie kregen, vertoonden minder angstgerelateerd gedrag, en reageerden sneller op pijnlijke prikkels, wat wijst op een hogere pijnsensitiviteit.
Een belangrijke kanttekening is wel dat niet in alle testen effecten van chemotherapie en/of butyraat werden gevonden. Zo zagen we bijvoorbeeld geen duidelijke veranderingen in werkgeheugen, leren, en geheugen. Ook wanneer we eenzelfde soort gedrag met verschillende testen onderzochten, gaven die testen niet altijd helemaal hetzelfde beeld.
Samengevat veroorzaakte chemotherapie veranderingen in gewicht, fysieke activiteit, angstgerelateerd gedrag, en pijnsensitiviteit van muizen. Butyraat kan een deel van deze veranderingen tegengaan, maar niet alle problemen verhelpen.
Van muis naar mens
Hoewel we niet in al onze testen effecten vonden van de chemotherapie of butyraatinterventie, is deze interventie toch veelbelovend. De veranderingen die chemotherapie veroorzaakte bij de muizen vertonen gelijkenissen met de psychologische, sensorische, en cognitieve klachten die patiënten na chemotherapie rapporteren. De positieve effecten van de butyraatinterventie bij muizen kunnen ook goed nieuws zijn voor mensen, omdat butyraat relatief makkelijk kan worden toegediend, bijvoorbeeld via voeding of supplementen. Een muis is echter geen mens, en een behandeling die in een dierenmodel werkt, laat zich niet automatisch vertalen naar patiënten. Meer onderzoek is dus nodig om te bepalen of butyraat ook bij mensen kan helpen. Dit onderzoek vormt echter een belangrijke eerste stap.
Chemotherapie redt levens. De volgende stap is ervoor zorgen dat patiënten hun leven zo goed mogelijk kunnen hervatten, want de strijd stopt niet altijd na de behandeling.
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