 The human gut microbiome is increasingly being studied due to its association with a range of diseases, including metabolic disorders, autoimmune diseases, cancer, and neurodevelopmentally disorders. Mouse models are commonly 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 data sets and discusses external factors that influence the capability of mouse models to recapitulate human diseases. Alternative model systems for gut microbiota research are also explored. This article was authored by Thylone on Myen, Savaera Silver, Adrienne Liston, and others.