Immunomodulation properties of multi-species fermented milks Benoît Folign  e a , Sandrine Parayre b, c , Redouane Cheddani b, c , Marie-H  el  ene Famelart b, c , Marie-No € elle Madec b, c , Coline Pl  e a ,J  er ^ ome Breton a , Jo € elle Dewulf a , Gw  ena € el Jan b, c , St  ephanie-Marie Deutsch b, c, * a Lactic Acid Bacteria & Mucosal Immunity, Center for Infection and Immunity of Lille, Institut Pasteurde Lille, INSERM-U 1019, CNRS UMR 8204 Universit e de Lille, 1 rue du Pr Calmette, BP 245, F-59019 Lille, France b INRA, UMR 1253 Science et Technologie du Lait et de l'Œuf, F-35042 Rennes, France c AGROCAMPUS OUEST, UMR1253 UMR Science et Technologie du Lait et de l' Œuf, F-35042 Rennes, France article info Article history: Received 10 July 2014 Received in revised form 24 March 2015 Accepted 7 April 2015 Available online xxx Keywords: Propionibacteria Propionibacterium freudenreichii Immunomodulation Anti-inflammatory Lactic acid bacteria Dairy abstract Dairy propionibacteria (PAB) are used as a ripening starter in combination with Lactic acid bacteria (LAB) for dairy products such as Swiss-type cheese. LAB and PAB have also been studied for their probiotic properties but little is still known about their individual and/or synergistic beneficial effects within dairy matrices. In the context of a rising incidence of Inflammatory Bowel Diseases, it has become crucial to evaluate the immunomodulatory potential of bacteria ingested in large numbers via dairy products. We therefore selected different strains and combinations of technological LAB and PAB. We determined their immunomodulatory potential by IL-10 and IL-12 induction, in human peripheral blood mononuclear cells, on either single or mixed cultures, grown on laboratory medium or directly in milk. Milk was fermented with selected anti-inflammatory strains of LAB or PAB/LAB mixed cultures and the resulting bacterial fractions were also evaluated for these properties, together with starter viability and optimum technological aspects. The most promising fermented milks were evaluated in the context of TNBS- or DSS-induced colitis in mice. The improvement in inflammatory parameters evidenced an alleviation of colitis symptoms as a result of fermented milk consumption. This effect was clearly strain-dependent and modulated by growth within a fermented dairy product. These findings offer new tools and perspectives for the development of immunomodulatory fermented dairy products for targeted populations. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction The human gastrointestinal tract is a complex ecosystem, in which resident and transiting bacteria co-exist. This microbiota fulfils important physiological and metabolic functions which include maintenance of the gut associated immune system (Purchiaroni et al., 2013). In some cases, dysbiosis, i.e. imbalanced intestinal microbiota, occurs. This leads to impairment of the im- mune function of the gut and chronic gastrointestinal illness can occur, associated with more or less severe symptoms, referred as “inflammatory bowel disease” (IBD) (Duboc et al., 2013). The po- tential role for some pathobionts in establishing and/or exacer- bating inflammation should not be disregarded (Kamada et al., 2013) and this may occur in the specific context of Crohn's disease-related polymorphisms, as recently confirmed in the case of adherent and enteroinvasive Escherichia coli (Nguyen et al., 2014). Nonetheless, reports have suggested that a lack of specific bacteria with anti-inflammatory properties in the dysbiosis accompanying IBD may also be responsible for gut inflammation (Eeckhaut et al., 2013; Kang et al., 2010; Morgan et al., 2012; Sokol et al., 2008). The association between the increased relative abundances of Faecalibacterium prausnitzii and extended remission periods in patients with Crohn's disease is obvious. Similarly, data showed that patients with IBD had lower faecal counts of the butyrate-producing bacteria Butyricoccus pullicaecorum, Roseburia hominis and F. prausnitzii (Eeckhaut et al., 2013; Machiels et al., 2014). In addition, representatives from the spore-forming Clos- tridium clusters IV and XIV are involved in the induction of toler- ance responses (T regulatory cells or Treg) in the colon (Atarashi et al., 2011). Targeting these resident bacteria is conceptually attractive as a potential therapy for treatment of these diseases. Indeed, referring to the observations made by Kang et al. (Kang * Corresponding author. INRA, UMR STLO, 65 rue de saint Brieuc, 35042 Rennes Cedex, France. Tel.: þ33 2 23 48 53 34. Contents lists available at ScienceDirect Food Microbiology journal homepage: www.elsevier.com/locate/fm http://dx.doi.org/10.1016/j.fm.2015.04.002 0740-0020/© 2015 Elsevier Ltd. All rights reserved. Food Microbiology xxx (2015) 1e10 Please cite this article in press as: Folign e, B., et al., Immunomodulation properties of multi-species fermented milks, Food Microbiology (2015), http://dx.doi.org/10.1016/j.fm.2015.04.002