(P04-071-24) Monostroma nitidum Derived Rhamnan Sulfate Protects Against NAFLD in ApoE-Knockout Mice Fed a Western Diet by Shifting Multi-omic Responses Along the Gut-Liver Axis

Objectives: Green alga (Monostroma nitidum) is rich in the polysaccharide rhamnan sulfate (RS), which shows anti-atherogenic activities in preclinical models. We hypothesized that dietary supplementation of RS-rich green alga powder (RS-GAP) would alleviate nonalcoholic fatty liver disease (NAFLD) through prebiotic and cardiometabolic activities at the gut and liver.

Methods: Male Apoe-knockout mice (11-wk, n = 18) were fed a Western diet containing 0% or 5% RS-GAP for 12-wk. Histological and biochemical evidence of NAFLD, inflammation, gut microbiota and short-chain fatty acids, and untargeted polar and nonpolar metabolites were examined.

Results: RS-GAP did not affect body or liver mass, but significantly reduced histological evidence of liver steatosis (P < 0.05). RS-GAP decreased serum cholesterol, LDL-C, triglyceride, and glucose without affecting serum aminotransferases or hepatic malondialdehyde. RS-GAP decreased the serum ratio of LPS binding protein to soluble CD14 while pro-inflammatory genes at liver (TNFα, IL-8, myeloperoxidase) and ileum (IL-6, myeloperoxidase) were upregulated. Ileum occludin mRNA was downregulated, and fecal calprotectin increased, but without affecting serum endotoxin. RS-GAP did not affect α-diversity of the gut microbiota, but shifted β-diversity while decreasing the abundance of Blautia and increasing Lachnospiraceae and increasing fecal butyrate concentration. RS-GAP altered the polar metabolome in fecal samples (93 metabolites decreased, 37 increased) and liver (3 metabolites decreased, 23 increased) as well as the hepatic lipidome (97 lipids decreased, 271 increased).

Conclusions: RS-GAP protects against NAFLD independent of an anti-inflammatory or antioxidant activity likely by regulating multi-omics responses along the gut-liver axis.

Funding Sources: Supported by Calroy Health Sciences