In people with obesity, statins may not only help to lower cholesterol and inflammation levels, but also improve gut composition and overall gut health, according to a recent study published in Nature.
Previous researchers have shown that imbalances in the composition of gut microbes are associated with a range of chronic diseases, including obesity, diabetes, inflammatory bowel disease, depression, and Parkinson disease. Additionally, poor diet and the use of some medications—like proton-pump inhibitors—can further disrupt the microbial communities in the gut.
“Whether initiating or sustaining pro-inflammatory processes and metabolic derailment, countering dysbiosis of the gut ecosystem has been suggested to contribute to the maintenance of host health and the containment of obesity-related comorbidities,” wrote the authors.
“However, no effective microbiome modulation strategy has yet been established,” they added.
Still, the link between the fecal microbiome and the development of obesity has piqued the curiosity of researchers ever since the inception of metagenomics—defined as the analysis of DNA obtained from environmental samples to analyze the microorganism flora without the need for unadulterated cultures. With this in mind, the researchers of the current study mined data from a cohort of 888 patients with a diverse range of BMIs to further investigate this microbiome-obesity link. The study was part of the European Union MetaCardis project—a large-scale observational cohort study that was created to analyze the role of gut microorganisms in the development of cardiometabolic diseases via metagenomic, metabolomic, and clinical approaches.
More than 42% of the participants noted taking at least one type of medication. The researchers, therefore, assessed the confounding effects of all drugs taken by more than 10% of the sample to look for any links between microbiota and obesity. The researchers found that statins had the largest explanatory power, and contributed to genus-level microbiome variation not fully accounted for by obesity-related parameters and metabolic syndrome features, including lipid and C-reactive protein levels. Of note, participants who took statins were most commonly prescribed simvastatin (48%), atorvastatin (31%), and other statins combined (21%).
The researchers searched for the Bacteroides2 (Bact2) enterotype, an intestinal microbiota frequently found in loose stools that exhibit a composition linked to systemic inflammation. Bact2 is characterized by high numbers of Bacteroides and few Faecalibacterium, as well as low microbial cell densities.
“Reported changes in stool consistency and inflammation status during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype,” wrote the authors.
They observed that microbiota dysbiosis related to obesity was negatively correlated with statin therapy, and led to a decreased Bact2 prevalence of 5.88% in obese participants taking statins. These findings were corroborated by two accompanying studies.
In participants not taking statins, the authors found that the prevalence of Bact2 was associated with BMI, and increased from 3.90% in those who were lean/overweight to 17.73% in those who were obese.
“Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation,” the authors explained.
The authors stressed that for the past several years, adjusting gut microbiota centered on probiotics and prebiotics, which expose or promote the growth of beneficial bacteria or bacterial mixes into the gut. Recently, however, there has been renewed interest in the impact of small drugs, small molecules, and fecal isolates into the gut.
“Within the limitations of the cross-sectional nature of the cohorts analyzed—and emphasizing the need for interventional follow-up research using a randomized, double-blind, placebo-control study design to exclude potential confounding by indication—our findings suggest statins as a possible target for the development of future drug-based strategies for the modulation of the intestinal microbiota,” the authors concluded.