The microbiome influences host processes including nutritional availability, development, immunity, and behavioral responses. is a powerful model to study molecular mechanisms of host-microbial interactions. Recent efforts have been made to profile the natural microbiome of , laying a foundation for mechanistic studies of host-microbiome interactions in this genetically tractable model system. Studies using single-species microbes, multi-microbial systems, and humanized worm-microbiome interaction studies reveal metabolic and microbial-microbial interactions relevant in higher organisms. This article discusses recent developments in modeling the effects of host-microbiome interactions in .