It is well established that incidence of heart disease are associated with alterations to the makeup of the gut microbiome. But exactly which changes in the gut, and whether these changes are a cause or consequence of heart disease has been an open question, say a team of German scientists behind a new study.
The systematic analysis, led by Professor Norbert Frey of the University Hospital Schleswig-Holstein, looks at the genetic makeup of the intestinal microbiome of 20 heart failure patients and 20 healthy controls to provide new understandings of how gut colonisation is linked with the development and progress of heart failure.
“To our knowledge, this is the first systematic analysis of the intestinal bacterial microbiota of HF patients using high-throughput sequencing of bacterial 16S rRNA gene sequences,” said the team, writing in ESC Heart Failure.
The results showed that a significantly lower variability of bacteria are found in the gut in patients with heart failure than in healthy people, and that individual important families of bacteria are significantly reduced.
“Our data point to an altered intestinal microbiome as a potential player in the pathogenesis and progression of heart failure,” added the German researchers.
The key differences between healthy individuals and those with heart failure were in the loss of bacteria of the genera Blautia and Collinsella, as well as two previously unknown genera that belong to the families Erysipelotrichaceae and Ruminococcaceae, said the team – who suggested the findings may point towards possible therapeutic strains.
Frey and colleagues sought to systematically investigate, if there are specific changes of the intestinal microbiome in heart failure patients by comparing intestinal microbiome of 20 patients with heart failure to 20 healthy case-matched controls using high-throughput sequencing of the bacterial 16S rRNA gene.
According to the Shannon diversity index (which measures the intra-individual alpha-diversity) based on the distribution of operational taxonomic units (OTUs), heart failure cases showed significantly lower diversity index compared to controls.
Furthermore, testing for genera abundance showed a tendency towards a decreased alpha diversity of heart failure patients, while beta-diversity measures (inter-individual diversity) also showed a highly significant separation of heart failure cases and controls.
“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,” said the authors.
Cause or consequence?
The team noted that previous research projects have shown that the occurrence of Blautia is linked to a reduction of inflammation, while Faecalibacterium is also associated with anti-inflammatory mechanisms.
And, since heart failure is accompanied by a chronic inflammation, one theory could be that these alterations to gut flora encourage such systemic inflammation.
However, most scientists currently believe that the gut flora changes as a consequence of heart failure.
The researchers behind the current study believe it is plausible that an altered bacterial profile could be a risk factor or an early disease marker for heart failure.
They suggest that this is supported by the recent characterisation of trimethylamine N-oxide (TMAO), a metabolic product of gut bacteria, as an independent risk factor for the mortality rate in patients with heart failure.
“It seems possible that altered bacterial gut colonisation, most likely the depletion of distinct core intestinal microbiota, acts as a risk factor and disease marker for HF, enhancing disease progression in a vicious cycle,” concluded the team – noting that future studies should focus on the likely mechanisms involved, such as altered inflammatory pathways.
Source: ESC Heart Failure
Published online, Open Access, doi: 10.1002/ehf2.12155
“Heart failure is associated with depletion of core intestinal microbiota”
Authors: Mark Luedde, et al