title: Propionibacterium freudenreichii component 1.4-dihydroxy-2-naphthoic acid (DHNA) attenuates dextran sodium sulphate induced colitis by modulation of bacterial flora and lymphocyte homing.
abstract: OBJECTIVE
  1.4-Dihydroxy-2-naphthoic acid (DHNA), a bifidogenic growth stimulator from Propionibacterium freudenreichii, is thought to have a beneficial effect as a prebiotic; however, its in vivo effect on intestinal inflammation remains unknown. The aim of this study was to determine whether oral administration of DHNA can ameliorate dextran sodium sulphate (DSS) induced colitis and to determine the possible underlying mechanisms.
  
  
  METHODS
  Colitis was induced in mice by treatment with 2.0% DSS for seven days. DHNA (0.6 or 2.0 mg/kg) was given in drinking water prior to (preventive study) or after (therapeutic study) DSS administration. Colonic damage was histologically scored, and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) expression and beta7 positive cell infiltration were determined by immunohistochemistry. mRNA levels of proinflammatory cytokines (interleukin (IL)-1beta, IL-6 and tumour necrosis factor alpha (TNF-alpha)) were determined by quantitative real time polymerase chain reaction. In addition, bacterial flora in the caecum, concentrations of short chain acids, and luminal pH were examined.
  
  
  RESULTS
  DHNA improved survival rate and histological damage score in mice administered DSS in both the preventive and therapeutic studies. DHNA significantly attenuated the enhanced expression of MAdCAM-1, the increased beta7 positive cell number, and the increased mRNA levels of IL-1beta, IL-6, and TNF-alpha in DSS treated colon. In addition, the decreased number of Lactobacillus and Enterobacteriaceae induced by DSS was recovered by DHNA. Preventive effects on decrease in butyrate concentration and decrease in pH level in mice administered DSS were also observed in the DHNA preventive study.
  
  
  CONCLUSIONS
  DHNA, a novel type of prebiotic, attenuates colonic inflammation not only by balancing intestinal bacterial flora but also by suppressing lymphocyte infiltration through reduction of MAdCAM-1.
authors.affiliation: Second Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa City, Saitama 359-8513, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuzuki
authors.forename: J
authors.initials: J
authors.lastname: Miyazaki
authors.forename: K
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: R
authors.initials: R
authors.lastname: Hokari
authors.forename: S
authors.initials: S
authors.lastname: Komoto
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: A
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: S
authors.initials: S
authors.lastname: Nagao
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Miura
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000032:analysis; D003092:Colitis / Q000378:metabolism / Q000517:prevention & control / Q000628:therapy*; D003106:Colon / Q000382:microbiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate; D005232:Fatty Acids, Volatile / Q000032:analysis; D005243:Feces / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D039641:Integrin beta Chains / Q000032:analysis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009088:Mucoproteins; D009284:Naphthols / Q000494:pharmacology / Q000627:therapeutic use*; D011424:Propionibacterium / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D015996:Survival Rate
chemical_list: D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D005232:Fatty Acids, Volatile; D039641:Integrin beta Chains; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D009284:Naphthols; D016201:Receptors, Lymphocyte Homing; C091368:integrin beta7; C024023:1,4-dihydroxy-2-naphthoic acid; D016264:Dextran Sulfate