The role of IL-6 in modulating gut microbiome diversity and hepatic health

Metabolic dysfunction associated steatotic liver disease (MASLD) is characterized by excessive lipid accumulation in hepatocytes in individuals who consume little to no alcohol. Under severe cases, simple steatosis and an imbalanced metabolism can be accompanied by inflammation and hepatocyte ballooning, which further contributes to liver damage. Although dysbiosis of the gut microbiome is associated with disease progression, exact mechanisms remain unclear. Interleukin 6 (IL-6) is a pleiotropic cytokine that plays crucial roles in the acute phase response as well as hepatocyte homeostasis and regeneration. The inflammatory activity of IL-6 signaling in the liver has been well characterized; however, its effects on modulating the gut microbiome are less understood. Therefore, this study aims to determine whether the protective role of IL-6 manipulates shifts in microbiome diversity in the setting of MASLD. We hypothesize IL-6 plays a central role in regulating microbiome diversity in response to diet. Six-month old C57BL6 mice were randomly assigned to one of four groups: Chow, Chow/IL-6-/-, Western, or Western/IL-6-/-, where IL-6-/- mice were deficient in IL-6. Following 12 weeks, standard measures of hepatic health were measured, including hepatic triglyceride content, lipid perxoxidation status, and serum transaminase levels. Hepatic histology and 16S rRNA sequencing are being prepared currently. Results showed mice consuming a Western diet had increased hepatic triglyceride content compared to chow mice regardless of IL-6 status. No differences among all groups were observed in hepatic lipid peroxidation. Transaminase analysis revealed Western IL-6-/- animals had significantly higher values than chow wild-type animals but not chow IL-6-/- mice. Further analysis on microbiota diversity and hepatic histology is forthcoming. Present data indicates that the Western diet significantly detriments hepatic health, however the role of IL-6 remains unclear. This project was funded by The USDA National Institute of Food and Agriculture (Hatch VT2024-HR05) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.