 The human gut's microbiome is gaining attention due to its association with various diseases such as obesity, type 2 diabetes, inflammatory bowel disease, cancer and neurodevelopmentally disorders. Mouse models are used in biomedical research to study the complex host microbiota interactions and develop mechanistic hypotheses, but pitfalls should be considered when translating results from mouse models to humans. This special article compares the human and murine core gut microbiota based on a meta-analysis of available datasets and discusses external factors that influence the capability of mouse models to recapitulate human diseases. Additionally, alternative model systems for gut microbiota research are explored. This article was authored by Thylone on New Yen, Saroviera Silver, Adrienne Liston and others.