The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL

Posted by: | October 18, 2019 | Comments

ABSTRACT

PDA is characterized by a distinctive intratumoral and gut mycobiome

Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1. However, the mycobiome has not been clearly implicated in tumorigenesis. Here we show that fungi migrate from the gut lumen to the pancreas, and that this is implicated in the pathogenesis of PDA. PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue. The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices. Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp. in both mice and humans. Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species—but not species in the genera Candida, Saccharomyces or Aspergillus—accelerated oncogenesis.

Read more at: Nature

Berk Aykut, Smruti Pushalkar, Ruonan Chen, Qianhao Li, Raquel Abengozar, Jacqueline I. Kim, Sorin A. Shadaloey, Dongling Wu, Pamela Preiss, Narendra Verma, Yuqi Guo, Anjana Saxena, Mridula Vardhan, Brian Diskin, Wei Wang, Joshua Leinwand, Emma Kurz, Juan A. Kochen Rossi, Mautin Hundeyin, Constantinos Zambrinis, Xin Li, Deepak Saxena & George Miller. Nature. DOI: https://doi.org/10.1038/s41586-019-1608-2. 02 Oct 2019.





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