Article Text

Download PDFPDF
Propionibacterium freudenreichii component 1.4-dihydroxy-2-naphthoic acid (DHNA) attenuates dextran sodium sulphate induced colitis by modulation of bacterial flora and lymphocyte homing
  1. Y Okada1,
  2. Y Tsuzuki1,
  3. J Miyazaki1,
  4. K Matsuzaki1,
  5. R Hokari1,
  6. S Komoto1,
  7. S Kato1,
  8. A Kawaguchi1,
  9. S Nagao1,
  10. K Itoh1,
  11. T Watanabe2,
  12. S Miura1
  1. 1Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan
  2. 2Laboratory of Animal Hygiene, Tokyo University of Agriculture, Kanagawa, Japan
  1. Correspondence to:
    Professor S Miura
    Second Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa City, Saitama 359-8513, Japan; miura{at}


Background and aim: 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.

Method: 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 β7 positive cell infiltration were determined by immunohistochemistry. mRNA levels of proinflammatory cytokines (interleukin (IL)-1β, IL-6 and tumour necrosis factor α (TNF-α)) 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 β7 positive cell number, and the increased mRNA levels of IL-1β, IL-6, and TNF-α 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.

Conclusion: 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.

  • DHNA, 1.4-dihydroxy-2-naphthoic acid
  • DSS, dextran sodium sulphate
  • IL, interleukin
  • TNF-α, tumour necrosis factor α
  • UC, ulcerative colitis
  • CD, Crohn’s disease
  • IBD, inflammatory bowel diseases
  • SCFA, short chain fatty acid
  • ECAM, endothelial cell adhesion molecule, ICAM-1, intercellular adhesion molecule 1
  • VCAM-1, vascular cell adhesion molecule 1
  • MAdCAM-1, mucosal addressin cell adhesion molecule 1
  • DW, distilled water
  • H&E, haematoxylin-eosin
  • PBS, phosphate buffered saline
  • PCR, polymerase chain reaction
  • mucosal addressin cell adhesion molecule 1
  • β7 integrin
  • prebiotics
  • bacterial flora
  • short chain fatty acids

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published online first 18 November 2005

  • Conflict of interest: none declared.

Linked Articles

  • Digest
    Robin Spiller Alastair Watson