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Faecal bacterial and short-chain fatty acids signature in hypercholesterolemia.

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PubMed ID: 30742005

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Granado-Serrano AB, Martín-Garí M, Sánchez V, Riart Solans M, Berdún R, Ludwig IA, Rubió L, Vilaprinyó E, Portero-Otín M, Serrano JCE

Sci Rep. Feb 2019. doi: 10.1038/s41598-019-38874-3

COMMENT: Hypercholesterolemia is an important risk factor of Cardiovascular diseases. Studies in mice have suggested that gut microbiota may affect lipid metabolism through bacterial metabolic products such as, short chain fatty acids (SCFAs), or bile acids (BA). There are few studies in humans about gut microbiota and their metabolites associated with host lipid metabolism. This study presents a proposal of a particular faecal bacterial signature associated to individuals with hypercholesterolemia.

Objective:

The aim of this study was to compare both the faecal microbiota composition and the SCFAs and BA profile of subjects with hypercholesterolemia (HC) and normocholesterolemia (NC) in order to determine whether hypercholesterolemia is associated with a particular faecal bacteria signature. In addition, correlations between these both parameters and a wide selection of lipid profile biomarkers, taking into account their particle size, were analysed.

Main results:

The assessment of bacterial species diversity did not display relevant differences between HC and NC subjects.

Taxonomic characterization analysis revealed some differences between the faecal bacterial communities of HC and NC subjects.

No differences were observed in dominant phyla such as Bacteroidetes or Firmicutes (HC, 49.58% vs NC, 51.13% and HC, 42.01% vs NC, 49.98%, respectively), and either in Proteobacteria…Nevertheless, there were three bacterial genera belonging to these phyla which were found to have different prevalence in both groups: Odoribacter (Bacteroidetes), Ruminoccocus (Firmicutes) and Haemophilus (Proteobacteria).

These differences seem to be intrinsically related to the subject physiology rather than to other external factors that have been reported to alter the gut microbiota composition, such as diet.

Only in the case of Ruminococcus, the differences observed were associated with age, so that further studies in a large cohort would be needed to confirm or discard its contribution to the faecal bacterial signature in this pathology.

The proposed specific faecal bacterial signature in individuals with hypercholesterolemia is characterized by lower relative abundance of both Anaeroplasma (Tenericutes) and Haemophilus (Proteobacteria) and higher relative abundance of both Odoribacter (Bacteroidetes) and Ruminococcus (Firmicutes) compared with normomocholesterolemic subjects.

Correlation analysis with serum lipid biomarkers support and stand out the relevance of these bacteria in hypercholesterolemia. Particularly, in the case of Haemophilus, a negative correlation with a common indicator of dyslipidaemia such as the Total-C to HDL-C ratio was observed.

It was observed that the lower abundance of Anaeroplasma, was associated with an unfavourable lipid profile (IDL-C, TG-related biomarkers and the ratio Total-C to HDL-C among others).

Faecal and serum total SCFAs were similar in HC and NC. Nevertheless, data from correlation analysis revealed that the faecal proportion of acetic acid correlated positively to IDL-C levels,whose high levels are indicative of a more unfavourable lipid profile,

Conclusions

This study revealed that individuals with hypercholesterolemia possess a particular faecal bacterial signature, characterized by lower prevalence of the genera Anaeroplasma and Haemophilus and higher prevalence of Odoribacter, which seems to be associated with a wide range of blood lipid biomarkers, including those ones commonly linked to a higher risk of CVDs and others..

It was observed in HC subjects a raise in isobutyric acid, whose higher abundance in the faeces could be considered as a biomarker in hypercholesterolemia.

The lower prevalence of both P. faecium and P. Succinatutens in the faeces of hyperhcolesterolemic subjects is suggested as another hallmark of the bacterial community dysbiosis associated with higher cholesterol levels but its involvement in the lipid profile is still unclear.

In spite of the relevant findings here shown, the authors assume that the study has some limitations. It was performed only in men, all of them from a specific area of Spain (Catalonia), the number of subjects was low and moreover, the number of healthy volunteers was lower than the hypercholesterolemic ones.

Contributor

Diana López-Farfán