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

Abstract

SCOPE\nPoly-pharmacological therapy shapes the gut microbiota (GM) in metabolic syndrome (MetS) patients. The effects of polyphenol-rich sources in poly-medicated MetS patients are unknown.\n\n\nMETHODS AND RESULTS\nA randomized, placebo-controlled, double-blinded, and crossover trial in poly-medicated MetS patients (n = 50) explored whether the effects of a pomegranate extract nutraceutical (PE, 320\xa0mg phenolics/day for one month) were affected by the drug therapy. We evaluated, considering the lipid-lowering (LL-), anti-hypertensive (HP-) and(or) anti-diabetic (AD-) treatments: GM (16S rRNA sequencing), short-chain fatty acids, 40 inflammatory-metabolic and endotoxemia-related biomarkers, associations between biomarkers and GM with 53 cardiometabolic dysfunctions-related single-nucleotide polymorphisms (SNPs), and the influence of urolithin metabotypes (UMs). Representative SNPs-GM associations after PE included Lactococcus and ClostridiumXIVa with rs5443-GNB3 and ClostridiumXIVa with rs7903146-TCF7L2 and rs1137101-LEPR. PE decreased sICAM-1 in LL-patients and the lipopolysaccharide-binding protein in all the patients. PE did not affect the other patients markers as a group or stratifying by UMs. After PE, Lactococcus increased in AD-, LL- and HP-patients, Bifidobacterium increased in LL- and AD-, while Clostridium XIVa decreased in non-LL- and non-HP-patients.\n\n\nCONCLUSION\nThe prebiotic effect of PE depended on the medication, mainly on HP-treatments. Targeting GM could complement MetS therapy, but the patients drug therapy should be considered individually. This article is protected by copyright. All rights reserved.