During the last years it became more and more obvious that the intestinal microbiota is pivotal for the intestinal and overall health of human beings. Consequently, the modulation of the intestinal microbiota in order to maintain or increase health gained a lot of attention. In this context, clinical studies revealed that the uptake of specific probiotic strains can indeed be effective in the prevention and reduction of a major disease of civilisation, inflammatory bowel disease. However, a broad, safe and effective use of probiotics in the clinic is hampered by the lack of mechanistic understanding. Specifically, there is almost nothing known regarding the molecular mechanisms that are induced by probiotics in the host or the bacterial structures that are responsible for the observed protective effect. The present work therefore aimed to unravel these questions with regard to a clinically relevant probiotic mixture, VSL#3. In summary, it was found that VSL#3 mediates selective post-translational degradation of a major proinflammatory chemokine, IP-10. The bacterial protease lactocepin, expressed by Lactocbacillus casei VSL#3, was identified to be the active anti-inflammatory probiotic structure. These findings enable a more structure-related evaluation of new probiotics as well as the future development of anti-inflammatory drugs based on probiotic lactocepin.