Heart failure is associated with depletion of core intestinal microbiota

Mark Luedde, Thorben Winkler, Femke-Anouska Heinsen, Malte C Rühlemann, Martina E Spehlmann, Amer Bajrovic, Wolfgang Lieb, Andre Franke, Stephan J Ott, Norbert Frey, Mark Luedde, Thorben Winkler, Femke-Anouska Heinsen, Malte C Rühlemann, Martina E Spehlmann, Amer Bajrovic, Wolfgang Lieb, Andre Franke, Stephan J Ott, Norbert Frey

Abstract

Aims: In spite of current medical treatment approaches, mortality of chronic heart failure (HF) remains high and novel treatment modalities are thus urgently needed. A recent theory proposes a possible impact of the intestinal microbiome on the incidence and clinical course of heart failure. This study sought to systematically investigate, if there are specific changes of the intestinal microbiome in heart failure patients.

Methods and results: The intestinal microbiome of 20 patients with heart failure with reduced ejection fraction due to ischemic or dilated cardiomyopathy was investigated by applying high-throughput sequencing of the bacterial 16S rRNA gene. Microbial profiles were compared to those of matched controls in which heart failure was ruled out by clinical assessment and NT-proBNP serum levels (n = 20). According to the Shannon diversity index (which measures the intra-individual alpha-diversity) based on the distribution of operational taxonomic units (OTUs), HF cases showed a nominally significantly lower diversity index compared to controls (Pnom. = 0.01), and testing for genera abundance showed a tendency towards a decreased alpha diversity of HF patients. Beta-diversity measures (inter-individual diversity) revealed a highly significant separation of HF cases and controls, (e.g. Pweighted UniFracv = 0.004). Assessing the individual abundance of core measurable microbiota (CMM), a significant decrease of Coriobacteriaceae, Erysipelotrichaceae and Ruminococcaceae was observed on the family level. In line with that, Blautia, Collinsella, uncl. Erysipelotrichaceae and uncl. Ruminococcaceae showed a significant decrease in HF cases compared to controls on the genus level.

Conclusions: Heart failure patients showed a significantly decreased diversity of the intestinal microbiome as well as a downregulation of key intestinal bacterial groups. Our data point to an altered intestinal microbiome as a potential player in the pathogenesis and progression of heart failure.

Keywords: 16S; Diversity; Gut microbiome; Heart failure; Microbiota.

© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
(A) Alpha diversity: Shannon Index based on OTU abundance for controls and HF patients. (B) Beta diversity: PCoA plot of weighted UniFrac distances.
Figure 2
Figure 2
Genus level abundances of CMM for controls and HF cases. (A) Mean relative abundances of the two groups. (B) Relative abundances for the individual samples.
Figure 3
Figure 3
Taxonomic groups of CMM (family to OTU level) found with different abundances between HF cases and controls. ns: not significant (P > 0.05), *: P < 0.05, **: P < 0.01, ***: P < 0.001. P‐values before and after correction for multiple testing are separated by the slash character.

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