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. Aim 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 16s 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 α-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.

中文翻译：

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心力衰竭引起的微生物失调导致小鼠结肠肿瘤的形成

简介 心力衰竭 (HF) 和癌症是全世界死亡的主要原因。流行病学研究表明心力衰竭患者容易患癌症。临床前研究对这种联系提供了一些见解，但确切的机制仍然难以捉摸。在结直肠癌 (CRC) 中，肠道微生物失调与癌症进展有关，最近的研究表明心力衰竭患者表现出微生物失调。目的 目前的研究重点是高频诱导的微生物失调对结肠肿瘤形成的影响。方法与结果C57BL/6J小鼠心肌梗死(MI)，以假手术作为对照。六周后收集粪便，进行 16s rRNA 测序处理，并汇集用于粪便微生物群移植。通过用氧化偶氮甲烷/葡聚糖硫酸钠处理无菌小鼠，引发结直肠癌肿瘤生长。CRC 小鼠被移植了 MI 或假小鼠的粪便。MI 诱导的心力衰竭导致微生物失调，其特征是 α 多样性减少和属水平的微生物改变，其中一些与结直肠癌相关。然后，我们将 HF 小鼠的粪便移植到 CRC 小鼠中，结果导致 CRC 小鼠的内窥镜疾病评分更高，肿瘤数量增加。结论 我们证明，心肌梗死诱导的心力衰竭通过改变肠道微生物群组成而促进结肠肿瘤的形成，为观察到的心力衰竭与癌症风险增加之间的关联提供了机制解释。针对微生物组可能会成为减轻心力衰竭相关并发症（尤其是癌症）的工具。