Helicobacter pylori-associated hypochlorhydria in children, and development of iron deficiency

Aims Acute Helicobacter pylori infection is associated with transient hypochlorhydria. In H pylori-associated atrophy, hypochlorhydria has a role in iron deficiency (ID) through changes in the physiology of iron-complex absorption. The aims were to evaluate the association between H pylori-associated hypochlorhydria and ID in children. Methods Symptomatic children (n=123) were prospectively enrolled. Blood, gastric juice and gastric biopsies were taken, respectively, for haematological analyses, pH assessment and H pylori determination, and duodenal biopsies for exclusion of coeliac disease. Stool samples were collected for parasitology/microbiology. Thirteen children were excluded following parasitology and duodenal histopathology, and five due to impaired blood analysis. Results Ten children were hypochlorhydric (pH>4) and 33 were H pylori positive. In H pylori-positive children with pH>4 (n=6) serum iron and transferrin saturation levels % were significantly lower (p<0.01) than H pylori-positive children with pH≤4. No differences in ferritin, or total iron binding capacity, were observed. In H pylori-negative children with pH>4, iron and transferrin saturation were not significantly different from children with pH≤4. Conclusions Low serum iron and transferrin in childhood H pylori infection is associated with hypochlorhydria. In uninfected children, hypochlorhydria was not associated with altered serum iron parameters, indicating a combination of H pylori infection and/or inflammation, and hypochlorhydria has a role in the aetiology of ID. Although H pylori-associated hypochlorhydria is transient during acute gastritis, this alters iron homeostasis with clinical impact in developing countries with a high H pylori prevalence.

A randomized comparison of quadruple and triple therapies for helicobacter pylori eradication: The QUADRATE study.

Background & Aims: Direct comparisons of bismuth and proton pump inhibitor (PPI)-based triple and quadruple therapies for Helicobacter pylori eradication are lacking. To address this, a randomized study was conducted.Methods: Infected dyspeptic patients received pantoprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all twice daily, for 7 days (PAC7); or pantoprazole 40 mg twice daily, bismuth subcitrate 108 mg, and tetracycline 500 mg, both 4 times daily, and metronidazole 200 mg 3 times daily and 400 mg at night for 7 days (PBTM7); bismuth subcitrate 108 mg and tetracycline 500 mg, both 4 times daily, and metronidazole 200 mg 3 times daily and 400 mg at night for 14 days (BTM14). Outcome was assessed with ¹³C-urea breath test.Results: Eradication rates (intention to treat [n = 405]/per protocol [n = 320]) were similar for PAC7 (78%/82%) and PBTM7 (82%/88%); the latter significantly superior to BTM14 (69%/74%; P < 0.01). Pretreatment metronidazole resistance (MR) was 53% and clarithromycin resistance was 8%. Eradication rates for primary metronidazole sensitive/resistant isolates were 74%/87% with PAC7 and 80%/81% for PBTM7, compared with 76%/55% (P < 0.02) for BTM14. Noncompliance was greater with BTM14 (15%; P < 0.001) than PAC7 (3%) or PBTM7 (6%). Moderate-severe adverse events were more common with BTM14 (45%; P < 0.001), than PAC7 (23%) or PBTM7 (25%) with more discontinuations (9%, 2%, 3%, respectively).Conclusions: One-week PPI triple therapy is well tolerated and effective. The addition of PPI to bismuth triple therapy allows reduction of treatment duration with improved efficacy and tolerability, despite a high rate of MR. Quadruple therapy appears to overcome pretreatment MR in most cases. Two-week bismuth triple therapy is significantly inferior to quadruple therapy and less well tolerated than both 1-week therapies.

Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells

Gram-negative bacterial peptidoglycan is specifically recognized by the host intracellular sensor NOD1, resulting in the generation of innate immune responses. Although epithelial cells are normally refractory to external stimulation with peptidoglycan, these cells have been shown to respond in a NOD1-dependent manner to Gram-negative pathogens that can either invade or secrete factors into host cells. In the present work, we report that Gram-negative bacteria can deliver peptidoglycan to cytosolic NOD1 in host cells via a novel mechanism involving outer membrane vesicles (OMVs). We purified OMVs from the Gram-negative mucosal pathogens: Helicobacter pylori, Pseudomonas aeruginosa and Neisseria gonorrhoea and demonstrated that these peptidoglycan containing OMVs upregulated NF-κB and NOD1-dependent responses in vitro. These OMVs entered epithelial cells through lipid rafts thereby inducing NOD1-dependent responses in vitro. Moreover, OMVs delivered intragastrically to mice-induced innate and adaptive immune responses via a NOD1-dependent but TLR-independent mechanism. Collectively, our findings identify OMVs as a generalized mechanism whereby Gram-negative bacteria deliver peptidoglycan to cytosolic NOD1. We propose that OMVs released by bacteria in vivo may promote inflammation and pathology in infected hosts.