Effects of a phenolic-rich grape pomace extract on intestinal barrier, gut microbiota, and adipose tissue in high-fat diet-fed mice.

Abstract

Obesity is associated with impaired intestinal barrier integrity, gut dysbiosis, and adipose tissue dysfunction, leading to endotoxemia and metabolic disturbances. We previously observed that grape pomace extract (GPE), rich in phenolic compounds, protected mice from high-fat diet (HFD)-induced endotoxemia and hepatic steatosis. This study aimed to evaluate the effect of GPE on intestinal permeability, gut microbiota composition, and the associated metabolic alterations in HFD-fed mice. Mice were assigned to four experimental groups and fed for 13 weeks with either a standard diet or HFD (approximately 60% total calories from fat) with or without GPE supplementation (300 mg of GPE/kg body weight/day). DNA was extracted from the cecal and colon contents and gut microbiota was analyzed using 16S rRNA gene sequencing. Mice fed a HFD developed obesity, increased adipose tissue mass, adipocyte hypertrophy, brown adipose tissue (BAT) whitening, and metabolic alterations. These changes were associated with endotoxemia, partial alterations in tight junction (TJ) protein expression, activation of inflammatory signaling pathways involved in TJ opening (IKK phosphorylation, and extracellular signal-regulated kinase (ERK 1/2)) in the colon. Additionally, HFD altered microbial diversity compared to control groups. GPE supplementation mitigated HFD-induced obesity, metabolic disturbances, and endotoxemia while also restoring specific aspects of colon morphology and intestinal barrier integrity. Notably, GPE led to a selective modulation of specific gut bacteria. Overall, GPE supplementation partially improved intestinal barrier markers and altered gut microbiota composition in HFD-fed mice, which was associated with reduced endotoxemia and improvements in obesity-related metabolic alterations, supporting its potential as a dietary strategy to mitigate HFD–induced metabolic disturbances.