Humans live in a permanent association with bacterial populations collectively called the microbiota. In the last 10 years, major advances in our knowledge of the microbiota have shed light on its critical roles in human physiology. The microbiota has also been shown to be a major factor in numerous pathologies including obesity or inflammatory disorders. Despite tremendous progresses, our understanding of the key functions of the human microbiota and the molecular basis of its interactions with the host remain still poorly understood. Among the factors involved in host colonization, two enzymes families, sulfatases and radical S-adenosyl-L-methionine enzymes, have recently emerged as key enzymes.