IDDF2018-ABS-0162 Altered gut microbiota in experimental mouse models of non-alcoholic fatty liver disease

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Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide and is thought to be strongly associated with gut microbiota. Several diet models were therefore built in mice to try to clarify the molecular mechanisms. However, how and to what extent these diet models alter the composition of the gut microbiota have not yet been clearly elucidated.

Methods

In this study, we developed three mouse models of NAFLD using methionine-choline-deficient (MCD) diet, high-fat (HF) diet, and choline-deficient- high-fat (CD-HF) diet, evaluated the severity of steatohepatitis and sequenced the faecal bacteria by targeting 16 S V4-V6 regions on Illumina MiSeq using PE 300 reagents.

Results

Histological scores showed that MCD induced the severest steatohepatitis, followed by HF and CD-HF diets. Based on operational taxonomic units (OTUs) at cutoff of 97% similarity, there were significant (PERMANOVA, p=0.001) differences in overall gut bacterial communities among MCD, HF, CD-HFD, and the Control, forming three major clusters in PCA ordination with HF and CD-HF groups more similar (figure 1). Furthermore, α-diversity of HF and CD-HF groups, including observed OTU numbers, Shannon index, and Pielou evenness were significantly (ANOVA, p<0.05) higher than the Control and MCD group. Overall, mouse gut bacteria were mainly composed of Fimicutes (Ruminococcaceae, Lachnospiraceae, Clostridiaceae) and Bacteroidetes (S24–7, Porphyromonadaceae). More specifically, Ruminococcus was significantly reduced in the three NAFLD models than the Control and was identified as the biomarker of NAFLD in LEfSe analysis. More biomarkers at genus level (Lachnospira, S24–7, etc.) were identified in pairwise comparison of one mice model with the Control.

Conclusions

In summary, the composition of gut microbiota varied remarkably between mice administrated different experimental diets to induce non-alcoholic fatty liver disease.

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