Altered Gut Microbiota Composition and Immune Response in Experimental Steatohepatitis Mouse Models

Mitsuaki Ishioka, Kouichi Miura, Shinichiro Minami, Yoichiro Shimura, Hirohide Ohnishi

Although several types of diet have been used in experimental steatohepatitis models, comparison of gut microbiota and immunological alterations in the gut among diets has not yet been performed. We attempted to clarify the difference in the gut environment between mice administrated several experimental diets. Male wild-type mice were fed a high-fat (HF) diet, a choline-deficient amino acid-defined (CDAA) diet, and a methionine-choline-deficient (MCD) diet for 8 weeks. We compared the severity of steatohepatitis, the composition of gut microbiota, and the intestinal expression of interleukin (IL)-17, an immune modulator. Steatohepatitis was most severe in the mice fed the CDAA diet, followed by the MCD diet, and the HF diet. Analysis of gut microbiota showed that the composition of the Firmicutes phylum differed markedly at order level between the mice fed the CDAA and HF diet. The CDAA diet increased the abundance of Clostridiales, while the HF diet increased that of lactate-producing bacteria. In addition, the CDAA diet decreased the abundance of lactate-producing bacteria and antiinflammatory bacterium Parabacteroides goldsteinii in the phylum Bacteroidetes. In CDAA-fed mice, IL-17 levels were increased in ileum as well as portal vein. In addition, the CDAA diet also elevated hepatic expression of chemokines, downstream targets of IL-17. The composition of gut microbiota and IL-17 expression varied considerably between mice administrated different experimental diets to induce steatohepatitis.