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Session: Big Data and Omics in Bioactives Research (Oral 15)

(OR15-05-23) Combined Application of Ellagic Acid and Urolithin-Producing Bacteria Enhanced Anti-Obesity Efficacy and Phenolic Bioavailability in Diet-Induced Obese Mice

Monday, July 24, 2023
8:48 AM – 9:00 AM ET
Location:  Commonwealth

    Presenting Author(s)

  • Danyue Zhao, PhD (she/her/hers)

    Assistant Professor
    The Hong Kong Polytechnic University
    Hong Kong, Hong Kong

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • YY

    Yang Yang

    The Hong Kong Polytechnic University

  • PL

    Pui-Kei Lee

    The Hong Kong Polytechnic University

  • KW

    Ke Wang

    The Hong Kong Polytechnic University

Disclosure(s):
Danyue Zhao, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Obesity has evolved into a global pandemic but safe and effective anti-obesity remedies are lacking. Dietary polyphenols, such as ellagic acid (EA), have purported anti-obesity effects and could serve as cost-effective therapeutics. As EA exhibits very low oral bioavailability, its bioefficacy is closely linked to its bioactive and bioavailable gut microbiota-derived metabolites, i.e., urolithins (Uros). However, not all individuals harbor Uro-producing bacteria. Thus, combining EA and Uro-producing bacteria, e.g., Gordonibacter urolithinfaciens (G.uro), could be a solution. This study aims to develop a novel synbiotic (SYN) integrating EA and G.uro for enhanced anti-obesity efficacy in high fat diet (HFD)-induced obese mice, and to explore the underlying mechanisms.

Methods: The synbiotic was prepared by dispensing EA and G.uro in a cyclodextrin solution (VEH). Male C57BL6/J mice fed on HFD were assigned to 7 groups orally gavaged with VEH, EA, SYN, UroC, G.uro, or pasteurized G.uro (pG), and a normal diet (ND) group. Body weight, energy expenditure, ambulatory activity, insulin sensitivity, blood lipids and EA/Uro excretion were measured at multiple time points. After 9 weeks, biosamples were collected for biochemical, histological, metabolomics and metagenomics analyses to provide mechanistic insights on SYN’s anti-obesity effects.

Results: The SYN was well tolerated in obese mice and remarkably enhanced EA and Uro bioavailability compared with dosing EA alone. Treatment with SYN, EA, G.uro and pG prevented excessive weight gain, improved lipid metabolism, and elicited higher energy expenditure under cold challenge compared with the HFD group. SYN also promoted adipose tissue browning as evidenced by the significantly upregulated expression of UCP1 and PRDM16 genes in subcutaneous fats. Interestingly, G.uro and pG also showed positive effects on fat browning. Furthermore, SYN better facilitated G.uro colonization and relieved gut dysbiosis in obese mice.

Conclusions: This is the first study to investigate the anti-obesity efficacy and lipid metabolism regulatory effects of the novel EA-G.uro synbiotic in obese mice. Our findings provide valuable preclinical evidence for the anti-obesity potential of this synbiotic and demonstrate promising translational value.

Funding Sources: National Natural Science Foundation of China (32101961)