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Pomegranate juice (PJ) and inulin have been reported to ameliorate diet-induced metabolic disorders by regulating gut microbiota dysbiosis. However, there was a lack of clinical evidence for the combined effects of PJ and inulin on regulating gut microbiota in individuals with metabolic disorders. A double-blind, parallel, randomized, placebo-controlled trial was conducted, and 68 overweight/obese individuals (25 ≤ BMI ≤ 35 kg/m2) were randomly assigned to receive 200 mL/d PJ, PJ supplemented with inulin, or placebo for 3 weeks. Our results showed that PJ and PJ+inulin did not significantly alter the levels of anthropometric and blood biochemical indicators after 3 weeks of treatment. However, there was an increasingly significant impact from placebo to PJ to PJ+inulin on the composition of gut microbiota. Detailed bacterial abundance analysis further showed that PJ+inulin treatment more profoundly resulted in significant changes in the abundance of gut microbiota at each taxonomic level than PJ. Moreover, PJ+inulin treatment also promoted the production of microbiota-associated short-chain fatty acids and pomegranate polyphenol metabolites, which correlated with the abundance of the bacterial genus. Our results suggested that PJ supplemented with inulin modulates gut microbiota composition and thus promotes the production of microbiota-associated metabolites that exert potential beneficial effects in overweight/obese subjects.

Pomegranate peel polyphenols (PPPs) and inulin have been reported to have lipid-lowering effects. Here, the effects of PPPs combined with inulin on obesity traits and the change of the gut microbiota, short-chain fatty acids (SCFAs), and serum metabolomics profiles in rats with a high-fat diet (HFD) were investigated. According to the experimental results, PPPs were most effective in reducing the body weight and serum and liver lipid levels. Besides, PPPs ameliorated the disorder of gut microbiota, in particular, the enrichment of SCFA producers, such as Lactobacillus, Roseburia, Christensenellaceae_R-7_group, Ruminococcaceae_UCG-005, Bacteroides, and Allobaculum,and the depletion of the Blautiaand unclassified Lachnospiraceaepopulation. PPPs also regulated the levels of metabolites changed by HFD feeding via tryptophan metabolism, valine, leucine, and isoleucine biosynthesis, and arachidonic acid metabolism pathways. The correlation analysis showed that PPPs remitted HFD-induced elevation in triglycerides (TGs), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels and lowered high-density lipoprotein (HDL) levels through regulating the gut microbiota, SCFAs, and related metabolites. These findings elucidated that PPPs have a good anti-obesity effect. This study extends the understanding of PPP effects on high-fat-induced obesity, which includes the relationship among gut microbiota, SCFAs, serum metabolites, and TG-, IL-6- and TNF-α- lowering and HDL-elevating functions.