title: The bifidogenic growth stimulator inhibits the growth and respiration of Helicobacter pylori.
abstract: BACKGROUND
  Triple therapy with amoxicillin, clarithromycin, and a proton-pump inhibitor is a common therapeutic strategy for the eradication of Helicobacter pylori (H. pylori). However, frequent appearance of clarithromycin-resistant strains is a therapeutic challenge. While various quinones are known to specifically inhibit the growth of H. pylori, the quinone 1,4-dihydroxy-2-naphthoic acid (DHNA) produced by Propionibacterium has strong stimulating effect on Bifidobacterium. We were interested to see whether DHNA could inhibit the growth of H. pylori in in vitro or in vivo experimental setting.
  
  
  METHODS
  The minimum inhibitory concentration (MIC) of DHNA was determined by the agar dilution method. The inhibitory action of DHNA on the respiratory activity was measured by using an oxygen electrode. Germ-free mice infected with H. pylori were given DHNA in free drinking water containing 100 μg/mL for 7 days.
  
  
  RESULTS
  DHNA inhibited H. pylori growth at low MIC values, 1.6-3.2 μg/mL. Likewise, DHNA inhibited clinical isolates of H. pylori, resistant to clarithromycin. However, DHNA did not inhibit other Gram negative or anaerobic bacteria in the normal flora of the human intestine. Both H. pylori cellular respiration and adenosine 5'-triphosphate (ATP) generation were dose-dependently inhibited by DHNA. Similarly, the culture filtrates of propionibacterial strains inhibited the growth of H. pylori, and oral administration of DHNA could eradicate H. pylori in the infected germ-free mice.
  
  
  CONCLUSIONS
  The bifidogenic growth stimulator DHNA specifically inhibited the growth of H. pylori including clarithromycin-resistant strains in vitro and its colonization activity in vivo. The bactericidal activity of DHNA was via inhibition of cellular respiration. These actions of DHNA may have clinical relevance in the eradication of H. pylori.
authors.affiliation: Department of Food and Nutrition, Faculty of Human Life Sciences, Senri Kinran University, Osaka, Japan. k-nagata@cs.kinran.ac.jp
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nagata
authors.forename: Sakiko
authors.initials: S
authors.lastname: Inatsu
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Harumi
authors.initials: H
authors.lastname: Sato
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kouya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000378:metabolism*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000254:growth & development*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009284:Naphthols / Q000008:administration & dosage* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011424:Propionibacterium / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D009284:Naphthols; C024023:1,4-dihydroxy-2-naphthoic acid; D010100:Oxygen