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Deutsche Zeitschrift für Onkologie 2019; 51(03): 108-112
DOI: 10.1055/a-0889-5345
Forschung
© Georg Thieme Verlag KG Stuttgart · New York

Die intestinale Mikrobiota in der Onkologie

The Intestinal Microbiota in Oncology
Burkhard Schütz
,
Heiko Hofmann
,
Ricarda Deutschbein
Further Information

Publication History

Publication Date:
24 May 2019 (online)

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Zusammenfassung

Das physiologische intestinale Mikrobiom (Bakterien des Darmes) ist wesentlich für Funktion und Integrität des Darmes. Mikrobiom-Abweichungen können für die onkologische Therapie wichtige Hinweise liefern: Ein vermehrtes Auftreten des als invasiv bekannten Sulfatreduzierers Fusobacterium nucleatum (FN) im Mikrobiom zeigt eine hohe Korrelation mit dem Auftreten des kolorektalen Karzinoms. Hintergrund ist die Eigenschaft von FN, am Darmepithel ein entzündliches Mikroklima zu erzeugen, das den Darm schädigt und die Tumorprogression ebenso fördert wie die durch FN erzeugte Freisetzung des Transkriptionsfaktors NF-κB über die Expression von Onkogenen und weiteren proinflammatorischen Genprodukten. Darüber hinaus lässt FN die T-Zell-Dichte und -Aktivität sinken und hemmt so die Tumorabwehr. Weiterhin aktivieren proentzündliche Zytokine den Abbau der Aminosäure Tryptophan (TRP) zu Kynurenin. Damit wird einerseits TRP der Proteinbio- und der Serotoninsynthese entzogen. Andererseits sind erhöhte Kynurenin-Spiegel mit verringerten Überlebensraten assoziiert, da Kynurenin immunsuppressiv wirkt. Eine Therapie, die auf den Darm, seine Mikrobiota und das Eindämmen der Entzündung abzielt, kann die negativen Auswirkungen eingrenzen und die Regeneration und Remission des Patienten unterstützen.

Abstract

The physiological intestinal microbiome (bacteria of the intestine) is essential for function and integrity of the intestine. Microbial deviations can provide important indications for oncological therapy: high frequency of the Fusobacterium nucleatum (FN), known as an invasive sulfate reducer, shows a high correlation with the occurrence of colorectal cancer. The background is that FN generates an inflammatory microclimate at the intestinal epithelium which damages the intestine and increases the tumor progression as well as the release of the transcription factor NF-κB via expression of oncogenes and other proinflammatory gene products. In addition, FN reduces T-cell density and activity and therefore inhibits the tumor defence. Furthermore, pro-inflammatory cytokines activate the degradation of the amino acid tryptophan (TRP) to kynurenine. Hence TRP lacks for the protein biosynthesis and serotonin synthesis. On the other hand, elevated kynurenine levels are associated with reduced survival rates as kynurenine has an immunsuppressive effect. A therapy targeting the intestine, its microbiota and diminishing of inflammation can inhibit those negative effects and support the regeneration and remission of the patient.

Schlüsselwörter

Mikrobiom - kolorektales Karzinom - Fusobacterium nucleatum - Entzündung - Tryptophan

Key words

Microbiome - colorectal carcinoma - Fusobacterium nucleatum - inflammation - tryptophan
 

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