(PTFS04-02-25) Egg Sphingomyelin Supplementation Attenuates Early-Stage Colitis and Modulates Gut-Liver Inflammatory Responses in a High-Fat Diet/DSS Mouse Model

Objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD), including metabolic dysfunction-associated steatohepatitis (MASH), is a prevalent liver disorder, especially among obese individuals. Gastrointestinal inflammation can worsen liver injury, contributing to MAFLD, as seen in over 40% of patients with inflammatory bowel disease (IBD). Dietary egg sphingomyelin (ESM) has shown potential in reducing colitis and liver injury in separate models of colitis and MASH. However, its effects in a combined colitis and MASH model have not been studied. The primary aim was to investigate if ESM can prevent MASH and associated liver injury amid concurrent intestinal inflammation in a mouse model of chronic colitis and MASH.

Methods: Male C57BL/6J mice were divided into five groups: low-fat diet (LFD), HFD, or HFD + DSS supplemented with 0%, 0.1% or 0.3% ESM. Obese MASH was induced via a 10-week HFD regimen. Chronic colitis was induced with three 7-day cycles of 1% dextran sulfate sodium (DSS), followed by 14-day recovery periods. Colitis severity was assessed using Disease Activity Index (DAI) scores. Cecal feces were analyzed for gut microbiota, liver histology was evaluated via H&E staining, and immune cell populations in liver and colon were assessed using flow cytometry.

Results: ESM supplementation with DSS resulted in a dose-dependent reduction in total DAI and weight loss during the initial DSS cycle, indicating protection against early-stage colitis. DSS did not affect food intake. ESM did not significantly impact liver weight, serum triglycerides, total cholesterol, or ALT. The DSS control diet increased colon CD11b+ leukocytes, which was reduced by 0.3% ESM, along with a decrease in colon pro-inflammatory, activated M1 macrophages. In HFD + DSS control mice, elevated liver macrophages (M1 and M2) and mast cells were significantly reduced by the 0.3% ESM diet. Liver histology showed reduced steatosis in DSS groups, though further analysis of ESM's effect is needed. ESM also altered gut microbiome diversity, as indicated by significant changes in Jaccard Index of beta diversity.

Conclusions: ESM supplementation reduced acute colitis severity, modulated liver immune cell populations, and altered gut microbiome diversity, suggesting a role in mitigating intestinal inflammation and modulating the gut-liver axis.

Funding Sources: Egg Nutrition Center