IBD constitute a growing public health concern in western countries. Inflammation is a key parameter involved in many non-communicable chronic diseases. Bacteria with anti-inflammatory properties are lacking in dysbiosis accompanying IBD. Selected strains of probiotic bacteria with anti-inflammatory properties accordingly alleviate symptoms and enhance treatment of ulcerative colitis in clinical trials. Such properties are also found in selected strains of dairy starters, including Propionibacterium freudenreichii and Lactobacillus delbrueckii, which are widely ingested. We investigated the possibility to develop a fermented dairy product, combining both starter and probiotic abilities of both lactic acid and propionic acid bacteria, designed to extend remissions in IBD patients. Methods & Results We developed a two-strain P. freudenreichii and L. delbrueckii-fermented experimental pressed cheese using strains previously selected for their anti-inflammatory properties. This cheese was made in fully mastered conditions and contained only the two selected strains. It was consumed daily by mice during five days before induction of acute colitis by trinitrobenzenesulfonic acid (TNBS). Outcomes of colitis induction were then monitored in mice consuming this cheese or a placebo dairy matrix. For the first time, consumption of a designer P. freudenreichii and Lactobacillus delbrueckii pressed cheese was shown to protect mice against experimental colitis, alleviating severity of symptoms, modulating local and systemic inflammation, as well as colonic oxidative stress and epithelial cell damages. As a control, the corresponding sterile dairy matrix failed to afford such protection. Conclusion We eat more bacteria through daily consumption of fermented dairy products then through functional food supplements. This offers a tremendous level to modulate the digestive tract through the intake of desired bacteria. This work reveals the probiotic potential of a mixture of lactic and propionic selected starters. A “two-in-one” ability is revealed for bacteria able both to produce a fermented dairy product and to modulate inflammation. Such an innovation opens new avenues for the reverse engineering development of anti-inflammatory fermented foods designed for target populations with IBD, and has provided evidences leading to an ongoing pilot clinical study in ulcerative colitis patients. This work was financed by the French National Agency for Research.