New research has suggested that statin therapy may reduce the prevalence of a particular gut ... [+]
Researchers have found that a particular combination of bacteria in the gut microbiome known to be associated with inflammation is more prevalent in obese people. However, the study found that this was not the case for obese people on statin drugs to lower cholesterol, raising the question as to whether these drugs could potentially be used to modulate the gut microbiome.
The new work published today in Nature looked at the prevalence of a particular microbiome configuration (enterotype) in fecal samples from 888 people from France, Germany and Denmark. By analyzing which bacterial species compromise the microbiome, they found a particular enterotype called Bact2 was more common in obese (17.7%) than lean people (3.9%).
Bact2 has been previously associated with gut inflammation and is found more commonly in people with Crohn’s disease and ulcerative colitis as well as diseases such as depression and multiple sclerosis, which are also thought to involve inflammation.
They also looked for markers of inflammation, finding that people with Bact2 had higher levels than would be predicted by their obesity status alone.
“There is evidence that the Bact2 enterotype is associated with a heightened inflammatory state,” said Christoph Thaiss, an Assistant Professor of Microbiology at the Perelman School of Medicine of the University of Pennsylvania who was not involved in the study. “What is less clear, however, is whether there is a causal relationship between this enterotype and systemic inflammation, or whether the microbiome changes occur secondary to the disease state,” Thaiss added.
The researchers then looked at samples from two additional groups of people, together comprising over 2,600 more individuals, to make sure that their findings were replicated, finding the same trends.
The study also found that obese people on statins, a common medication prescribed to lower cholesterol and improve heart heath, were less likely to have the Bact2 microbiome configuration, with only 5.9% of obese people on statins having Bact2.
“There have been prior studies looking at the effect of statins on the gut microbiome. Some of them were carried out in animal models, where it is easier to determine causality,” said Thaiss. However, there isn’t currently any clear evidence yet that statins are responsible for this.
According to Thaiss, these studies have provided some evidence that statins can modulate the microbiome, but it still isn’t known whether this effect is directly due to the drug directly impacting the microbiome, or due to a knock-on effect of the intended effect of statins, which is to reduce the production of a type of cholesterol by the liver.
“One possible explanation for these findings is that statins exert a beneficial effect on the metabolic state of the patient, thereby lowering systemic inflammation. This, in turn, could lead to the microbiome changes that have been observed in this study. An alternative explanation is that statins, since they are taken orally, directly influence the bacterial population residing in the gut,” said Thaiss.
There has been some previously published evidence that statins can directly affect bacterial growth, but whether this direct effect is happening in people is still not entirely clear and further trials are required to investigate the link.
“It will be critical to perform randomized, double-blind, placebo-control studies to verify a direct causative effect of statins on the microbiome. If this is established, the next question will be whether the microbiome-modulating effect of statins are actually beneficial for human health,” said Thaiss.
Investigations into microbiome composition and how this can affect human health have exploded in number in recent years, with researchers looking at everything from how the microbiome affects conditions such as colorectal cancer, multiple sclerosis and even depression. However, although researchers are making inroads into understanding the microbiome, the idea of modulating it to improve human health or treat disease, is still in its infancy.
“Despite the growing knowledge about the impact of the microbiome on several human diseases, there are currently only very few therapeutic options for modulating the microbiome in a way that is beneficial for host health. Observational studies like this one could be the first step towards this goal,” said Thaiss.
As for the potential use of statins for modulating the microbiome, this study provides more useful information but more trials are needed to further investigate this.
“If the authors’ conclusions are confirmed by future prospective clinical trials, this finding may open exciting possibilities for using statins as microbiota-modulating therapeutics,” said Thaiss.
