Heart failure-induced microbial dysbiosis contributes to colonic tumour formation in mice

Sanne De Wit, Lotte Geerlings, Canxia Shi, Just Dronkers, Elisabeth M. Schouten, Gillian Blancke, Vanessa Andries, Tess Yntema, Wouter C. Meijers, Debby P.Y. Koonen, Lars Vereecke, Herman H.W. Silljé, Joseph Pierre Aboumsallem, Rudolf A. De Boer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Introduction Heart failure (HF) and cancer are the leading causes of death worldwide. Epidemiological studies revealed that HF patients are prone to develop cancer. Preclinical studies provided some insights into this connection, but the exact mechanisms remain elusive. In colorectal cancer (CRC), gut microbial dysbiosis is linked to cancer progression and recent studies have shown that HF patients display microbial dysbiosis.Aims This current study focussed on the effects of HF-induced microbial dysbiosis on colonic tumour formation.Methods and results C57BL/6J mice were subjected to myocardial infarction (MI), with sham surgery as control. After six weeks faeces were collected, processed for 16 s rRNA sequencing, and pooled for faecal microbiota transplantation. CRC tumour growth was provoked in germ-free mice by treating them with Azoxymethane/Dextran sodium sulphate. The CRC mice were transplanted with faeces from MI or sham mice. MI-induced HF resulted in microbial dysbiosis, characterized by a decreased alpha-diversity and microbial alterations on the genus level, several of which have been associated with CRC. We then performed faecal microbiota transplantation with faeces from HF mice in CRC mice, which resulted in a higher endoscopic disease score and an increase in the number of tumours in CRC mice.Conclusion We demonstrated that MI-induced HF contributes to colonic tumour formation by altering the gut microbiota composition, providing a mechanistic explanation for the observed association between HF and increased risk for cancer. Targeting the microbiome may present as a tool to mitigate HF-associated co-morbidities, especially cancer.Graphical abstract
Original languageEnglish
Pages (from-to)612-622
Number of pages11
JournalCardiovascular Research
Volume120
Issue number6
DOIs
Publication statusPublished - 1 Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.

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