Functional Swiss-type cheeses promote beneficial effects on mice health and gut microbiome during inflammatory bowel disease

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Rabah, Houem | Carvalho, Rodrigo D | Aburjaile, Flávia, Figueira | Rosa Do Carmo, Fillipe Luiz | Caetano Faria, Ana, Maria | Oliveira, Emiliano, Rosa | Garric, Gilles | Harel-Oger, Marielle | Guédon, Eric | Le Loir, Yves | de Carvalho Azevedo, Vasco Ariston | Jan, Gwénaël

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International audience. AbstractBackgrounds & Aims. Inflammatory Bowel Diseases (IBD), including Ulcerative Colitis (UC), coincide with alterations of the gut microbiota. Immunomodulatory probiotic bacteria may induce or prolong remission in UC patients. Fermented foods, including cheeses, constitute major sources of bacteria. New in vivo evidences revealed anti-inflammatory effects in selected strains of the dairy bacterium Propionibacterium freudenreichii , used as a cheese ripening starter. We thus hypothesized that consumption of a functional cheese, fermented by such a selected strain, may exert a positive effect on IBD.Methods. We developed an experimental single-strain cheese solely fermented P. freudenreichii CIRMBIA-129. We moreover produced, in industrial conditions, an Emmental cheese using the same strain, in combination with Lactobacillus delbrueckii CNRZ327 and Streptococcus thermophilus LMD-9, as starters. We tested both cheeses, in healthy conditions and as preventive food in the context of Dextran Sodium Sulphate (DSS)-induced colitis in mice. We monitored the gut microbiota of mice using shotgun metagenomic sequencing. We assessed the taxonomic and functional profiles through sequence alignment to NCBI taxonomy and KEGG pathways databases.Results. The experimental cheese and the Emmental cheese, both fermented by P. freudenreichii, reduced severity of subsequent DSS-induced colitis, weight loss, disease activity index and histological score. Both reduced small bowel IgA secretion, restored occludin gene expression and prevented induction of TNFα, IFNγ and IL-17. None of the cheeses disturbed the microbial community ecology in healthy conditions. Emmental intake increased symbionts as Romboutsia and Akkermansia muciniphila. Metabolic pathway analysis suggests that A. muciniphila may produce bioactive metabolites as acetate and cooperate with other commensal species to produce indole and gamma-aminobutyric acid. Some of the impaired microbiome metabolic functions, in colitis mice, were restored by single strain cheese, while Emmental promoted an increase in Ligilactobacillus murinus. This taxon presented several genes with immunomodulatory activity potential.Conclusions. Combinations of starter bacteria immunomodulatory strains lead to anti-inflammatory cheeses, as revealed in an animal model of colitis. Such cheeses may restore beneficial bacteria in the gut microbiota. Further studies are undertaken to investigate their role in regulating the gut-brain axis. This opens new perspectives for personalised nutrition in the context of IBD.

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