Strengths and limitations of <i>in vitro</i> and animal models to advance understanding of human diet‒microbiome interactions

The gut microbiome is a critical mediator of human health. As the intestinal microbiota is far more metabolically diverse than humans, it plays a significant role in the digestion of food, particularly food components that are nutritionally inaccessible to the human host. While no system can fully recapitulate the in vivo interactions of food, the host, and the gut microbiome in the human body, in vitro and animal model tools are critical for studying these complex relationships. Here, we review many of the common in vitro and animal models used to manipulate and study how the gut microbiome affects and is affected by diet. We focus on colonic fermentation systems, with or without small intestinal contribution, bioreactors with both microbial and host epithelial cell components, and animal models that have been developed to study these relationships. We will review the limitations of these systems while also discussing new innovations that seek to address these limitations.