The intestinal tract of metazoans harbors a dense collection of microbes known as the gut microbiota. In humans, this contains approximately a hundred trillion bacteria. The microbiota impacts host health through digestion, immune system tuning, and pathogen protection, though dysregulation can promote inflammatory diseases and cancer. The immune system regulates microbiota activity through complex symbiosis and bidirectional dialogue, with bacteria responding to immune stimuli at the transcriptional level. The laboratory uses immunological and microbiological models with sequencing approaches to dissect this relationship, aiming to generate knowledge for promoting health by inhibiting detrimental microbe activities and enhancing protective functions through genetic engineering of probiotics.