title: Immunoregulatory mechanisms underlying prevention of colitis-associated colorectal cancer by probiotic bacteria.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) increases the risk of colorectal cancer. Probiotic bacteria produce immunoregulatory metabolites in vitro such as conjugated linoleic acid (CLA), a polyunsaturated fatty acid with potent anti-carcinogenic effects. This study aimed to investigate the cellular and molecular mechanisms underlying the efficacy of probiotic bacteria in mouse models of cancer.
  
  
  RESULTS
  The immune modulatory mechanisms of VSL#3 probiotic bacteria and CLA were investigated in mouse models of inflammation-driven colorectal cancer. Colonic specimens were collected for histopathology, gene expression and flow cytometry analyses. Immune cell subsets in the mesenteric lymph nodes (MLN), spleen and colonic lamina propria lymphocytes (LPL) were phenotypically and functionally characterized. Mice treated with CLA or VSL#3 recovered faster from the acute inflammatory phase of disease and had lower disease severity in the chronic, tumor-bearing phase of disease. Adenoma and adenocarcinoma formation was also diminished by both treatments. VSL#3 increased the mRNA expression of TNF-α, angiostatin and PPAR γ whereas CLA decreased COX-2 levels. Moreover, VSL#3-treated mice had increased IL-17 expression in MLN CD4+ T cells and accumulation of Treg LPL and memory CD4+ T cells.
  
  
  CONCLUSIONS
  Both CLA and VSL#3 suppressed colon carcinogenesis, although VSL#3 showed greater anti-carcinogenic and anti-inflammatory activities than CLA. Mechanistically, CLA modulated expression of COX-2 levels in the colonic mucosa, whereas VSL#3 targeted regulatory mucosal CD4+ T cell responses.
authors.affiliation: Center for Modeling Immunity to Enteric Pathogens, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America. jbassaga@vt.edu
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
authors.forename: Monica
authors.initials: M
authors.lastname: Viladomiu
authors.forename: Mireia
authors.initials: M
authors.lastname: Pedragosa
authors.forename: Claudio
authors.initials: C
authors.lastname: De Simone
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003092:Colitis / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000150:complications / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D018928:Immunity, Mucosal / Q000187:drug effects; D044243:Linoleic Acids, Conjugated / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D016207:Cytokines; D044243:Linoleic Acids, Conjugated