Microalgal Unsaponifiable Matter Ameliorates Estrogen Deficiency-Induced Metabolic Dysfunction Through Intestinal Barrier Restoration and Gut Microbiota Modulation

Abstract

Estrogen deficiency contributes to intestinal barrier dysfunction, inflammation, and metabolic disturbances during the postmenopausal period. This study investigated the protective potential of microalgal unsaponifiable matter (MU) derived from Chlorella sp. against epithelial disruption and metabolic impairments associated with estrogen deficiency. MU was evaluated in tumor necrosis factor-α-challenged Caco-2 cells and ovariectomized mice. In vitro, MU (5–20 µg/mL) preserved cell viability, restored transepithelial electrical resistance (TEER), and maintained tight junction proteins while suppressing nuclear factor kappa-light-chain-enhancer of activated B cells–related cytokine expression. In vivo, MU improved feed efficiency, high-density lipoprotein cholesterol, and hepatic enzyme markers and reduced systemic and adipose tissue inflammation. MU also enhanced intestinal barrier integrity, increased mucin 2 expression, and partially normalized gut microbiota composition, including improvements in the Firmicutes/Bacteroidetes ratio. These compositional changes were associated with improvements in metabolic and inflammatory parameters, though causal relationships between specific microbial taxa and functional outcomes remain to be established. Collectively, these findings suggest that MU supports intestinal barrier protection, attenuates inflammation, and is associated with improved metabolic outcomes under estrogen-deficient conditions