NASH-associated gut microbiome in human microbiota-associated NAFLD mouse model

• Main Author: Tan, Jovi Siying
• Other Authors: Tan Nguan Soon
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2023
• Subjects: Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/166533
• Institution: Nanyang Technological University

Nonalcoholic fatty liver disease (NAFLD) is a forthcoming epidemic that is currently the leading cause of chronic liver disease worldwide. By 2030, it is projected to become the primary indication for liver transplantation. Yet, there is still inconsistency and lack of conclusive evidence regarding specific gut microbial communities contributing to disease pathogenesis and how they can be manipulated to alter disease susceptibility and progression. Therefore, this study characterized gut microbiota changes following NAFLD onset, using a humanized diet-induced NAFLD murine model. We first validated the significant impacts of dietary habits on the humanized gut microbiome during nonalcoholic steatohepatitis (NASH) development, and proved the sufficiency of fecal microbiota transplantation (FMT) in establishing a humanized mouse gut microbiome. Subsequently, we compared the composition and diversities of the humanized gut microbiome resulting from different diets, revealing key microbes involved in NAFLD pathogenesis and their dynamics in the gut microbiome. Lastly, a comparative analysis of our key findings with that of human studies in literature demonstrated the translatability of our results to human NAFLD. This study employed a novel method of incorporating distinct diets with humanized gut microbiome in murine to investigate NAFLD pathogenesis, resulting in more human-relevant findings.