Effects of a Resistant Starch Diet on Mouse Gut Microbiome Inadequately Translates to Findings in a Human Model

Résumé

Resistant starch diets are shown to provide various health benefits in humans due to the production of short-chain fatty acids from the gut microbiota. However, there is still ongoing debate on how to effectively study the effects of resistant starch consumption on human metabolism and body functions. While animal models, particularly mice, offer useful insights into biological processes and allow for controlled experiments, their relevance to human physiology and disease susceptibility is oftentimes challenged. This study compares the impact of a resistant starch diet on gut microbiome composition and function between human and humanized mouse models to determine the acceptability of mouse models for comparative analysis with humans. Using datasets from a human and humanized mouse study, significant differences were observed in both alpha and beta diversity metrics, indicating distinct microbial composition between human and mouse cohorts. Additionally, few shared taxa were found among all groups, indicating notable differences in microbial composition. Differential abundance analysis further highlighted significant differences between human and mouse groups, while PICRUSt2 analysis indicated divergent gut microbiome functions between the human and mouse model. Overall, these findings suggest that the humanized mouse model may not adequately represent the gut microbiome response to resistant starch diet observed in humans, emphasizing the need for cautious interpretation and investigation when extrapolating animal model results to human health contexts.