There is No Distinctive Gut Microbiota Signature in the Metabolic Syndrome: Contribution of Cardiovascular Disease Risk Factors and Associated Medication

Abstract

The gut microbiota (GM) has attracted attention as a new target to combat several diseases, including metabolic syndrome (MetS), a pathological condition with many factors (diabetes, obesity, dyslipidemia, hypertension, etc.) that increase cardiovascular disease (CVD) risk. However, the existence of a characteristic taxonomic signature associated with obesity-related metabolic dysfunctions is under debate. To investigate the contribution of the CVD risk factors and(or) their associated drug treatments in the composition and functionality of GM in MetS patients, we compared the GM of obese individuals (n = 69) vs. MetS patients (n = 50), as well as within patients, depending on their treatments. We also explored associations between medication, GM, clinical variables, endotoxemia, and short-chain fatty acids. Poly-drug treatments, conventional in MetS patients, prevented the accurate association between medication and GM profiles. Our results highlight the heterogeneity of taxonomic signatures in MetS patients, which mainly depend on the CVD risk factors. Hypertension and(or) its associated medication was the primary trait involved in the shaping of GM, with an overabundance of lipopolysaccharide-producing microbial groups from the Proteobacteria phylum. In the context of precision medicine, our results highlight that targeting GM to prevent and(or) treat MetS should consider MetS patients more individually, according to their CVD risk factors and associated medication.

Gallstone Disease, Obesity and the Firmicutes/Bacteroidetes Ratio as a Possible Biomarker of Gut Dysbiosis

“…In recent years, attention has been focused on the potential impact of the gut microbiota on the pathogenesis of pigment and cholesterol gallstones. It is proved that intestinal dysbiosis makes a significant contribution to the development of not only the GSD itself [ 5 , 6 , 79 , 80 , 81 , 82 ], but also to the development of numerous disorders that are risk factors for GSD, including obesity [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ], type 2 diabetes [ 83 ], hypercholesterolemia [ 20 , 52 ], diet [ 84 ], NAFLD [ 85 , 86 , 87 , 88 ], cardiovascular diseases [ 68 , 89 ], physical inactivity [ 29 , 90 , 91 ], etc.…”

“…Gut microbiota is changing with human development and is influenced by many confounding variables which could prevent the existence of a unique taxonomic signature as a standard feature for obesity and associated comorbidities such as GSD [ 64 , 83 , 89 ].…”

“…The presence of pathological conditions (diabetes mellitus [ 83 ], cardiovascular disease [ 89 ], inflammatory bowel disease [ 64 ], etc.). For example, the sphincter of Oddi laxity is associated with cholangiolithiasis, probably due to enhanced reflux of intestinal contents that change the microenvironment [ 112 ].…”

Pharmacological Therapy Determines the Gut Microbiota Modulation by a Pomegranate Extract Nutraceutical in Metabolic Syndrome: A Randomized Clinical Trial

“…These patients recently participated in a baseline study that explored the associations between their gut microbiota and their primary CVD risk factor and (or) their associated medication. [ 24 ] The protocol was registered at clinicaltrials.gov as NCT04075032. The patients were randomly divided into two arms using a computerized random number list.…”

“…Besides, an overabundance of lipopolysaccharide‐producing microbial groups from the Proteobacteria phylum was observed. [ 24 ] Therefore, there is no distinctive gut microbiota signature in MetS patients under drug therapy to serve as a standard target for prebiotics. [ 24 ]…”