title: Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice.
abstract: One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms - bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.
authors.affiliation: Institute of Microbiology of Academy of Sciences of Czech Republic, v.v.i., Prague, Czech Republic.
authors.forename: T
authors.initials: T
authors.lastname: Hudcovic
authors.forename: J
authors.initials: J
authors.lastname: Kolinska
authors.forename: J
authors.initials: J
authors.lastname: Klepetar
authors.forename: R
authors.initials: R
authors.lastname: Stepankova
authors.forename: T
authors.initials: T
authors.lastname: Rezanka
authors.forename: D
authors.initials: D
authors.lastname: Srutkova
authors.forename: M
authors.initials: M
authors.lastname: Schwarzer
authors.forename: V
authors.initials: V
authors.lastname: Erban
authors.forename: Z
authors.initials: Z
authors.lastname: Du
authors.forename: J M
authors.initials: JM
authors.lastname: Wells
authors.forename: T
authors.initials: T
authors.lastname: Hrncir
authors.forename: H
authors.initials: H
authors.lastname: Tlaskalova-Hogenova
authors.forename: H
authors.initials: H
authors.lastname: Kozakova
mesh_terms: D000208:Acute Disease; D000285:Administration, Rectal; D000818:Animals; D018988:Bacterial Translocation; D002087:Butyrates / Q000378:metabolism*; D039481:CD11b Antigen / Q000096:biosynthesis / Q000235:genetics; D048014:Clostridium tyrobutyricum / Q000502:physiology*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D005227:Fatty Acids / Q000378:metabolism; D007121:Immunocompetence; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D055262:Mucin-2 / Q000096:biosynthesis / Q000235:genetics; D009077:Mucins / Q000096:biosynthesis; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D019936:Probiotics / Q000627:therapeutic use*; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D062826:Zonula Occludens-1 Protein
chemical_list: D002087:Butyrates; D039481:CD11b Antigen; D005227:Fatty Acids; D020382:Interleukin-18; D008565:Membrane Proteins; C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D016264:Dextran Sulfate