Combined use of epigallocatechin-3-gallate (EGCG) and caffeine in low doses exhibits marked anti-obesity synergy through regulation of gut microbiota and bile acid metabolism

Food Funct. 2021 May 11;12(9):4105-4116. doi: 10.1039/d0fo01768j.


Epigallocatechin-3-gallate (EGCG) and caffeine constitute the most effective ingredients of weight loss in tea. However, whether combination of EGCG and caffeine exhibits anti-obesity synergy remains unclear. Here, we showed low-doses of EGCG and caffeine used in combination led to synergistic anti-obesity effects equivalent to those of high-dose EGCG. Furthermore, combination treatment exhibited a synergistic effect on altering gut microbiota, including decreased Firmicutes level and increased Bifidobacterium level. Other notable effects of combination treatment included synergistic effects on: increasing fecal acetic acid, propionic acid, and total SCFAs; decreasing expression of GPR43; and increasing microbial bile salt hydrolase gene copies in the gut, facilitating generation of unconjugated BAs and enhancing fecal BA loss. Additionally, combination treatment demonstrated synergistic effects toward increasing the expression of hepatic TGR5 and decreasing the expression of intestinal FXR-FGF15, resulting in increased expression of hepatic CYP7A1. Thus, the synergistic effect may be attributed to regulation of gut microbiota and BA metabolism.

MeSH terms

  • Animals
  • Anti-Obesity Agents / administration & dosage*
  • Bile Acids and Salts / analysis
  • Bile Acids and Salts / metabolism*
  • Caffeine / administration & dosage*
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Cholesterol 7-alpha-Hydroxylase / metabolism
  • Drug Synergism
  • Drug Therapy, Combination
  • Fatty Acids, Volatile / analysis
  • Fatty Acids, Volatile / metabolism
  • Feces / chemistry
  • Gastrointestinal Microbiome / drug effects*
  • Liver / metabolism
  • Male
  • Obesity / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, G-Protein-Coupled / metabolism


  • Anti-Obesity Agents
  • Bile Acids and Salts
  • Fatty Acids, Volatile
  • Gpbar1 protein, rat
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • farnesoid X-activated receptor
  • Caffeine
  • Catechin
  • epigallocatechin gallate
  • CYP7A1 protein, rat
  • Cholesterol 7-alpha-Hydroxylase