title: Physiological recycling of endogenous nitrate by oral bacteria regulates gastric mucus thickness.
abstract: BACKGROUND
  Inorganic nitrate from exogenous and endogenous sources is accumulated in saliva, reduced to nitrite by oral bacteria and further converted to nitric oxide (NO) and other bioactive nitrogen oxides in the acidic gastric lumen. To further explore the role of oral microbiota in this process we examined the gastric mucus layer in germ free (GF) and conventional mice given different doses of nitrate and nitrite.
  
  
  METHODS
  Mice were given either nitrate (100mg/kg/d) or nitrite (0.55-11 mg/kg/d) in the drinking water for 7 days, with the lowest nitrite dose resembling the levels provided by swallowing of fasting saliva. The gastric mucus layer was measured in vivo.
  
  
  RESULTS
  GF animals were almost devoid of the firmly adherent mucus layer compared to conventional mice. Dietary nitrate increased the mucus thickness in conventional animals but had no effect in GF mice. In contrast, nitrite at all doses, restored the mucus thickness in GF mice to the same levels as in conventional animals. The nitrite-mediated increase in gastric mucus thickness was not inhibited by the soluble guanylyl cyclase inhibitor ODQ. Mice treated with antibiotics had significantly thinner mucus than controls. Additional studies on mucin gene expression demonstrated down regulation of Muc5ac and Muc6 in germ free mice after nitrite treatment.
  
  
  CONCLUSIONS
  Oral bacteria remotely modulate gastric mucus generation via bioactivation of salivary nitrate. In the absence of a dietary nitrate intake, salivary nitrate originates mainly from NO synthase. Thus, oxidized NO from the endothelium and elsewhere is recycled to regulate gastric mucus homeostasis.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Joel
authors.initials: J
authors.lastname: Petersson
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Jädert
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Mia
authors.initials: M
authors.lastname: Phillipson
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Borniquel
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. Electronic address: jon.lundberg@ki.se.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Electronic address: lena.holm@mcb.uu.se.
authors.forename: Lena
authors.initials: L
authors.lastname: Holm
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria; D005753:Gastric Mucosa / Q000187:drug effects / Q000382:microbiology / Q000473:pathology*; D008297:Male; D051379:Mice; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000494:pharmacology*; D010084:Oxidation-Reduction; D060888:Real-Time Polymerase Chain Reaction; D012463:Saliva / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D009077:Mucins; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide
keywords: Gut microbiota; Nitric oxide; Nitrite; Nitrosothiols; Ulcer