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

Scope Poly-pharmacological therapy shapes the gut microbiota (GM) in metabolic syndrome (MetS) patients. The effects of polyphenols in poly-medicated MetS patients are unknown. Methods and results A 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 mg phenolics/day for 1 month) are affected by the drug therapy. 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 urolithin metabotypes (UMs) influence are evaluated. Representative SNPs-GM associations after PE include Lactococcus and ClostridiumXIVa with rs5443-GNB3 (G-protein-beta-polypeptide-3) and ClostridiumXIVa with rs7903146-TCF7L2 (transcription-factor-7-like-2) and rs1137101-LEPR (leptin-receptor). PE decreases sICAM-1 in LL-patients and the lipopolysaccharide-binding protein in all the patients. PE does not affect the other patients' markers as a group or stratifying by UMs. After PE, Lactococcus increases in AD-, LL-, and HP-patients, Bifidobacterium increases in LL- and AD-, while Clostridium XIVa decreases in non-LL- and non-HP-patients. Conclusion The prebiotic effect of PE depends on the medication, mainly on HP-treatments. Targeting GM can complement MetS therapy, but the patients' drug therapy should be considered individually.

Automated summary

The study found that pomegranate extract nutraceutical has an effect on the gut microbiota in poly-medicated MetS patients, particularly in anti-hypertensive treatments. This provides a new complementary approach for MetS therapy.