Abstract
Background
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.
Aim
We attempted to clarify the difference in the gut environment between mice administrated several experimental diets.
Methods
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.
Results
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.
Conclusions
The composition of gut microbiota and IL-17 expression varied considerably between mice administrated different experimental diets to induce steatohepatitis.
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Abbreviations
- ALT:
-
Alanine transaminase
- CDAA:
-
Choline-deficient amino acid-defined
- F/B :
-
Firmicutes/Bacteroidetes
- HF:
-
High-fat
- H&E:
-
Hematoxylin and eosin
- IL:
-
Interleukin
- MCD:
-
Methionine-choline-deficient
- NAFLD:
-
Nonalcoholic fatty liver disease
- NASH:
-
Nonalcoholic steatohepatitis
- NC:
-
Normal chow
- SCFAs:
-
Short-chain fatty acids
- TLR:
-
Toll-like receptor
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Acknowledgments
We thank Daichi Nakagawa for excellent technical assistance and the Biotechnology Center, Faculty of Bioresource Sciences, Akita Prefectural University, for assistance with the GS Junior instrument for pyrosequencing analyses.
Funding
This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (K.M.).
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Supplemental Figure 1
Composition of gut microbiota examined by the GS Junior system. The relative abundance of gut microbiota is shown for HF, CDAA, and MCD diets, compared with the NC group. First, the percentage of the gut microbiota was calculated in the total count reads (NC: 10,829, HF: 13,374, CDAA: 26,009, MCD: 22,601 reads). Red indicates increased abundance, while green indicates decreased abundance, compared with the NC group. The composition of the gut microbiota is shown at phylum, order, genus, and species level. (A) Composition of gut microbiota in phylum Firmicutes. “C” indicates Clostridium. (B) Composition of gut microbiota in phylum Bacteroidetes. “B” and “P” indicate Bacteroides and Parabacteroides, respectively. (C) Composition of gut microbiota in phylum Proteobacteria. “D” and “H” indicate Desulfovibrio and Helicobacter, respectively. (TIFF 2927 kb)
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Ishioka, M., Miura, K., Minami, S. et al. Altered Gut Microbiota Composition and Immune Response in Experimental Steatohepatitis Mouse Models. Dig Dis Sci 62, 396–406 (2017). https://doi.org/10.1007/s10620-016-4393-x
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DOI: https://doi.org/10.1007/s10620-016-4393-x