Original articleColonization of an acid resistant Kingella denitrificans in the stomach may contribute to gastric dysbiosis by Helicobacter pylori
Introduction
Helicobacter pylori (H. pylori) colonizes approximately half of the world's population and causes chronic gastritis, peptic ulcers, and gastric adenocarcinoma [1]. Eradication of this bacterium improves the symptoms of patients with peptic ulcer and gastric lymphoma of mucosa-associated lymphoid tissue [2], [3]. Isolation of H. pylori from endoscopic gastric biopsy specimens is the most reliable method for detecting H. pylori infection and essential for drug susceptibility testing [4].
The gastric acid determines bacterial susceptibility to the stomach and inhibits infectious agents from reaching the intestine [5]. Urease activity is crucial for H. pylori to colonize the stomach through neutralizing the acidic environment and providing chemotactic motility [6]. However, colonization of urease-negative H. pylori and Campylobacter jejuni is reported in patients receiving acid-reducing compounds [7], [8]. Moreover, predisposed decrease of acid secretion, due to therapy, disease, or age, increased bacterial population in gastric juice [9], [10]. Disproportional use of proton pump inhibitors is considered to promote small intestinal bacterial overgrowth, which is prevalent in patients with irritable bowel disease (IBD) [11]. The gastrointestinal microbiota clearly contributes to development of IBD both in mouse models and patients [12].
A gram-negative bacillus, Kingella denitrificans (K. denitrificans), is a component of the normal upper respiratory and genitourinary tract flora and sometimes causes severe infection [13], [14], [15]. Kingella species are plump gram-negative bacilli and positive for cytochrome c oxidase [16]. Unlike the related species, such as Neisseriae and Moraxellae, Kingella species are catalase-negative similar to Cardiobacterium hominis and Eikenella corrodens. However, strain UB-75 of Kingella oralis and strain UB-204 of E. corrodens were catalase positive [17]. The type-strain of K. denitrificans characteristically produces acid from glucose and is positive for prolyl-aminopeptidase. Different from other species in the genus, K. denitrificans reduces nitrate to nitrite [16].
Necessity for careful identification of urease-negative bacteria in the gastric mucosa is highlighted in this paper. Of particular interest, disruption of integrated immunological niche by dysbiotic colonization of commensal bacteria is discussed.
Section snippets
Patient
A 78-year-old man suffering from gastric ulcer had been administered 40 mg of histamine receptor 2 (H2) antagonist, ranitidine, per day for two years. Endoscopic observation revealed multiple gastric ulcer scars with severe atrophic gastritis. Gastric mucosal biopsy from the antrum and the body was performed to determine histological findings and detect H. pylori. The biopsy specimen was positive for the CLO-test (Kimbarly-Clark, Roswell, GA).
The study was approved by the Yamaguchi University
Isolation of a gram-negative and urease-negative bacterium
The histology of the gastric biopsy specimens indicated grandular atrophy and intestinal metaplasia accompanied by infiltration of mononuclear cells to the lamina propria, a typical observation in gastric mucosa infected with H. pylori (Fig. 1A). Though it is not specific, a few bacteria-like organisms could be seen in the gastric lumen (Fig. 1B). H. pylori ureA gene was amplified in the paraffin-embedded gastric tissue (not shown).
A bacterium isolated from the culture of biopsy specimen was
Discussion
The gastric juice represents a barrier to microbes in saliva and ingested food, mainly by the bactericidal activity of hydrochloric acid [23]. A study in patients with hypochlorhydria being treated with anti-acid and histamine receptor 2 (H2) antagonists identified bacteria originating from the mouth in the gastric contents [24]. Moreover, acid-inhibiting proton pump inhibitors caused gastric colonization by oral-type bacteria in healthy volunteers [10]. The gastric barrier to infection has
Conflict of interest
The authors declare no financial or commercial conflict of interest.
Acknowledgments
The authors are grateful to M. Kimoto for providing the electronmicrograph. This work was funded partly by a Grant for Joint Research Program of the Institute for Genetic Medicine, Hokkaido University (to H.Y.) and partly by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Science and Technology of Japan (no. 2500163603 to Y.H.).
References (33)
- et al.
Endocarditis caused by Kingella denitrificans
J Infect
(1993) Kingella kingae: from medical rarity to an emerging paediatric pathogen
Lancet Infect Dis
(2004)- et al.
Salmonella typhimurium diarrhea: switching the mucosal epithelium from homeostasis to defense
Curr Opin Immunol
(2011) - et al.
Helicobacter pylori: gastric cancer and beyond
Nat Rev Cancer
(2010) - et al.
Helicobacter pylori infection and the development of gastric cancer
N Engl J Med
(2001) Gastric lymphoma of mucosa-associated lymphoid tissue and Helicobacter pylori
Annu Rev Med
(1998)- et al.
Optimal combination of media for primary isolation of Helicobacter pylori from gastric biopsy specimens
J Clin Microbiol.
(1997) - et al.
Influence of gastric acid on susceptibility to infection with ingested bacterial pathogens
Infect Immun
(2008) - et al.
Chemotaxis and motility of Helicobacter pylori in a viscous environment
J Gastroenterol
(1999) - et al.
Characteristics of a clinical isolate of urease-negative Helicobacter pylori and its ability to induce gastric ulcers in Mongolian gerbils
Helicobacter
(2005)
Campylobacter jejuni in the stomach
J Med Microbiol
Fasting hypochlorhydria with Gram positive gastric flora is highly prevalent in healthy old people
Gut
Intragastric bacterial activity and nitrosation before, during, and after treatment with omeprazole
Br Med J
Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors?
Am J Gastroenterol
The impact of the microbiota on the pathogenesis of IBD: lessons from mouse infection models
Nat Rev Microbiol.
Retropharyngeal abscess from an unusual organism-Kingella denitrificans-in a patient on low-dose methotrexate
Ear Nose Throat J
Cited by (6)
High throughput sequence profiling of gut microbiome in Northern Indian infants during the first four months and its global comparison
2018, Meta GeneCitation Excerpt :In addition, the presence of K. denitrificans was also reported in these samples. K. denitrificans is reported to be a commensal of the human respiratory tract and is also reported to increase the acid tolerance of Helicobacter pylori during co-cultivation studies (Okamoto et al., 2014). The Bifidobacterial population in this cohort increased over the course of four months with B. adolescentis was the predominant species followed by B. longum and B. bifidum (Fig. 3a).
Gastric microflora and gastric disease
2019, World Chinese Journal of DigestologyBacterial Diversity of the Gastric Content of Preterm Infants during Their First Month of Life at the Hospital
2017, Frontiers in NutritionDysbiotic infection in the stomach
2015, World Journal of GastroenterologyPathogenesis of Helicobacter pylori Infection
2014, Helicobacter
- 1
Two authors contributed equally to the work.