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Cholesterol-lowering drugs associated with improved gut bacteria profile in obese individuals

Statins, the commonly prescribed class of drugs to reduce cardiovascular disease risk, are identified as a potential microbiota-modulating therapeutic, according to a new study.

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The microbiome, the genetic material of all microorganisms that live in the human body, is essential for development, immunity and nutrition. Cardiometabolic diseases (CMDs) like heart disease and metabolic disorders such as obesity and diabetes are associated with dysfunction in the microbiome. Research into this field has intensified in recent years. The gut microbiome, which refers to the genetic material of the gut microbiota, the complex microorganisms (bacteria, yeast and viruses) that are present in the gastrointestinal tract, has attracted particular attention in relation to CMDs. In addition, it’s known that the use of some medications, such as stomach acid neutralisers, is associated with disruption of the gut’s microbial communities. A team of scientists partially supported by the EU-funded METACARDIS project has explored gut bacteria in about 900 participants from Denmark, Germany and France. The researchers published their findings in the journal ‘Nature’, where they identified statins – the common cholesterol-lowering class of drugs – as a potential microbiota-modulating therapeutic. A news release by METACARDIS project partner University of Copenhagen states: “The intestinal microbiota in obese individuals had previously been shown to differ from those in lean subjects with a poor bacterial diversity, a relative depletion of health promoting bacteria and the remaining bacteria dominated by an inflammatory tone.” As noted in the same news release, the scientists “now define a cluster of bacteria called Bact2 enterotype, which is found in 4 % of lean and overweight people but in 18 % of obese individuals who did not use statin drugs, a group of cholesterol lowering medications.” The news release adds: “However, in other obese study participants who were treated with statins, the prevalence of the unhealthy Bact2 enterotype was significantly lower (6 %) than in their non-treated counterparts (18 %) – comparable to levels observed in non-obese participants (4 %). The same trend was validated in a Flemish study sample of about 2000 participants.”

Statin therapy

As explained in the news release, statins are used to lower the risk of developing cardiovascular diseases like coronary heart disease and over 200 million people worldwide are prescribed this group of medications. “Besides their cholesterol-lowering effects, statins also tend to appease patients’ systemic inflammation levels which in part may be related to a disrupted gut microbiota. The results suggest that statins could potentially modulate the disrupted gut microbiota and linked inflammation in obesity.” The researchers point out that the study results should be interpreted carefully because they are based on cross-sectional analyses, as opposed to following a treatment timeline. This means causality can’t be claimed based on these observations, nor can they exclude the role of unaccounted factors in the results. For example, statin-medicated participants might have adopted a radically healthy lifestyle after being diagnosed with an increased risk of developing CMD, which could have had an impact on their gut ecosystem. In the ‘Nature’ publication, they emphasise “that the cross-sectional design of our study does not allow us to rule out potential confounding by indication (lower Bact2 prevalence resulting from the specific condition that prompted statin prescription) or by unaccounted diagnosis-associated diet or lifestyle alterations (participants adopting health-promoting and/or microbiota-modulating activities complementary to statin therapy).” The METACARDIS (Metagenomics in Cardiometabolic Diseases) project ran between 2012 and 2018. It focused on the interaction between the gut microbiota, host health and CMD. For more information, please see: METACARDIS project website

Keywords

METACARDIS, gut bacteria, cardiometabolic disease, CMD, statins, gut microbiota

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