Effects of acid suppression on microbial flora of upper gut

Abstract

Decreased acid secretion, due to therapy or disease, predisposes to increased bacterial counts in gastric juice. As bacterial numbers increase, the number of nitrate-reducing strains and the concentration of luminal nitrite usually also increase. However, there is controversy (mainly because of assay problems) about whether decreased acid increases generation of N-nitroso compounds: these may be produced by acid or by bacterial catalysis, and the relative contributions of each are still uncertain. Other potentially important factors include ascorbate secretion (can prevent nitrite conversion to nitroso compounds) and the particular spectrum of nitroso compounds produced. Nitrosation of several histamine H2-receptor antagonists has been demonstrated experimentally, but under conditions that are very unlikely to be encountered clinically. Some acid suppressant therapies have been claimed to aid eradication of Helicobacter pylori, but more work is needed to evaluate this. If ulcer treatment regimens do not also address eradication of H. pylori (when present), gastritis will progress, and the recently documented association between H. pylori and gastric carcinoma needs to be considered. Enteric flora probably also increase if acid secretion is markedly reduced: this does not appear to have nutritional consequences but probably reduces the resistance to occasional infections, of which cholera is the best documented.

The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis

“…54 Studies found a logarithmic relationship between intragastric pH and median bacterial counts in the gastric juice and mucosa and increased risks for enteric infections and bacterial diarrhea. 55,56 A review of the literature notes that multiple non-H. pylori organisms have been isolated from the stomach in hypochlorhydric patients, including Lactobacillus spp, Streptococcus spp, Pseudomonas spp, Xanthomonas spp, Proteus spp, Klebsiella spp, Neisseria spp, Escherichia coli, and Campylobacter jejuni. 54 Acid suppressive drugs also affect the progression of H. pylori pathogenesis.…”

Achlorhydria is associated with gastric microbial overgrowth and development of cancer: Lessons learned from the gastrin knockout mouse

“…Furthermore, given a pH v4, ascorbic acid in the gastric juice competes for the nitrosation species instead of converting them to nitric oxide (NO). Formation of N-nitrosamines does not increase during long-term PPI treatment (for instance 20-40 mg omeprazole daily) [86]; long-term treatment is generally considered safe in man [109]. However, extended follow-up periods are still desirable [110], especially since today's regimes are much more aggressive.…”

“…The molecular events underlying gastric carcinogenesis are still poorly understood, but seem to be a multistep process, as suggested by Correa [84]. Complete blockade of acid secretion may thus be undesirable, as this favours bacterial overgrowth [85,86] and subsequent generation of carcinogenic substances [87,88]. Among these are the N-nitrosamines, which can be found in increased amounts in achlorhydric patients [89,90].…”

The Chemistry of Protein Modifications Elicited by Nitric Oxide and Related Nitrogen Oxides

“…This is also known to occur within the oral and gut flora. Nitrite is formed from nitrate by the reductive activity of commensal bacteria in the oral cavity to end up via swallowed saliva as acidified nitrite in the stomach (Correa et al, 1975;Duncan et al, 1995;McKnight et al, 1997;Yeomans et al, 1995). It has been proposed that this nitrite has antimicrobial properties (McKnight et al, 1999).…”