Since the discovery in the 1600s of microscopic organisms, scientists have investigated the relationship between our health and the microbes that surround and inhabit us. Nowadays, we acknowledge that some microbes are inherently pathogenic, but also that others live mutualistically on and within our bodies and contribute to maintaining our well-being. Yet, one prominent challenge remains: to convincingly move past mere association and prove causality. Our microbiotas have been increasingly associated with various diseases, including obesity, but demonstrating a relationship between cause and effect is essential — particularly for the development of targeted therapeutics.