Inflammatory bowel diseases (IBDs), such as Crohn’s disease and ulcerative colitis, affect more than 0.3% of the Western population. The sheer complexity of these diseases presents a major challenge to treatment, as it has created a disconnect between microbiologists studying the effects of the microbiome, immunologists studying immune responses, and clinicians who treat individuals with IBD. To mount a more holistic approach, researchers recently examined the crosstalk between immune cells and bacteria in the colon. Experiments revealed the significance of bacterial products called outer membrane vesicles, or OMVs. OMVs are tiny sacs of cellular material released by bacteria as a way of communicating with immune cells. In patients with Crohn’s disease or ulcerative colitis, OMVs elicited only a small fraction of their normal immune response, suggesting a breakdown in immune–microbiota communication. Graduating from the test tube to live experiments could clarify the communication pathways OMVs present and provide individuals with IBD the benefit of a whole-body approach to treatment.