Mol. Nutr. Food Res. 2016, 60, 935–948 935 DOI 10.1002/mnfr.201500580 RESEARCH ARTICLE Combining selected immunomodulatory Propionibacterium freudenreichii and Lactobacillus delbrueckii strains: Reverse engineering development of an anti-inflammatory cheese Coline Pl ´ e 1 ,J´ er ˆ ome Breton 1 , Romain Richoux 2 , Marine Nurdin 2 , St ´ ephanie-Marie Deutsch 3,4 , H´ el ` ene Falentin 3,4 , Christophe Herv ´ e 5 , Victoria Chuat 3,4,6 , Riwanon Lem ´ ee 5 , Emmanuelle Maguin 7,8 , Gw ´ ena ¨ el Jan 3,4 , Maarten Van de Guchte 7,8 and Benoit Folign ´ e 1 1 Institut Pasteur de Lille, Lactic Acid Bacteria & Mucosal Immunity, Center for Infection and Immunity of Lille, Lille, France 2 Actalia Produits Laitiers, Agrocampus Ouest, Rennes cedex, France 3 Science et Technologie du Lait et de l’Œuf, INRA, Rennes, France 4 Agrocampus Ouest, Rennes, France 5 Laboratoires Standa, Caen, France 6 CIRM-BIA, Centre Internationale de Ressources Microbiennes–Bact ´ eries d’Int ´ er ˆ et Alimentaire, Rennes, France 7 INRA, Jouy-en-Josas, France 8 AgroParisTech, UMR Micalis, Jouy-en-Josas, France Received: July 23, 2015 Revised: November 25, 2015 Accepted: November 29, 2015 Scope: Inflammatory bowel disease (IBD) constitutes a growing public health concern in western countries. Bacteria with anti-inflammatory properties are lacking in the 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 such as Propionibacterium freudenreichii and Lactobacillus delbrueckii (Ld). We thus 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 and results: We developed a single-strain Ld-fermented milk and a two-strain P. freudenreichii and Ld-fermented experimental pressed cheese using strains previously se- lected for their anti-inflammatory properties. Consumption of these experimental fermented dairy products protected mice against trinitrobenzenesulfonic acid induced 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: This work reveals the probiotic potential of this bacterial mixture, in the context of fermented dairy products. It opens new perspectives 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. Keywords: Colitis / Dairy Starter / Gut / Inflammation / Probiotic Correspondence: Gw ´ ena ¨ el Jan E-mail: gwenael.jan@rennes.inra.fr Abbreviations: CTL, control; IBD, inflammatory bowel disease; Ld, Lactobacillus delbrueckii; MPO, myeloperoxidase; MTX, ma- trix; Pf, Propionibacterium freudenreichii; TNBS, trinitrobenzene- sulfonic acid; UHT, ultra-high temperature 1 Introduction Inflammatory bowel disease (IBD) constitutes a growing health concern in developed countries. It comprises a group of multifactorial ailments favored by a genetic background Colour Online: See the article online to view Figs. 2, 4, 6, and 7 in colour. C  2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.mnf-journal.com