Ethanol-derived Microbial Production of Carcinogenic Acetaldehyde in Achlorhydric Atrophic Gastritis

Background: Acetaldehyde is a local carcinogen in the digestive tract in humans. Atrophic gastritis leads to microbial colonization of the stomach, which could enhance microbial production of acetaldehyde from ethanol. The aim of the study was to study microbial ethanol metabolism and acetaldehyde production in the stomach of achlorhydric atrophic gastritis patients. Methods: For the in vivo study, glucose or ethanol was infused via a nasogastric tube to the stomach of seven achlorhydric atrophic gastritis patients and five healthy controls. Gastric juice samples for ethanol and acetaldehyde determinations and microbial analysis were obtained at 30 and 60 min after the infusions. For the in vitro study, gastric juice samples from 14 atrophic gastritis patients and 16 controls were obtained during gastroscopy, whereafter the samples were incubated for 2 h with 1% ethanol at 37 °C and acetaldehyde was determined. Results: Minor endogenous ethanol and acetaldehyde concentrations were detected after glucose infusion in the gastric juice of four atrophic gastritis patients. After ethanol infusion, the mean intragastric acetaldehyde level of the atrophic gastritis patients was 4.5-fold at 30 min and 6.5-fold at 60 min compared to controls. In vitro, the difference between the study groups was even higher, 7.6-fold. A vast selection of oral bacterial species and some Enterobacteriaceae and yeasts were presented in the gastric juice of atrophic gastritis patients. Conclusions: Microbial ethanol metabolism leads to high intragastric acetaldehyde levels after ethanol drinking in achlorhydric atrophic gastritis patients. This could be one of the factors responsible for enhanced gastric cancer risk among atrophic gastritis patients.     

Ethanol-derived microbial production of carcinogenic acetaldehyde in achlorhydric atrophic gastritis

BACKGROUND: Acetaldehyde is a local carcinogen in the digestive tract in humans. Atrophic gastritis leads to microbial colonization of the stomach, which could enhance microbial production of acetaldehyde from ethanol. The aim of the study was to study microbial ethanol metabolism and acetaldehyde production in the stomach of achlorhydric atrophic gastritis patients. METHODS: For the in vivo study, glucose or ethanol was infused via a nasogastric tube to the stomach of seven achlorhydric atrophic gastritis patients and five healthy controls. Gastric juice samples for ethanol and acetaldehyde determinations and microbial analysis were obtained at 30 and 60 min after the infusions. For the in vitro study, gastric juice samples from 14 atrophic gastritis patients and 16 controls were obtained during gastroscopy, whereafter the samples were incubated for 2 h with 1% ethanol at 37 degrees C and acetaldehyde was determined. RESULTS: Minor endogenous ethanol and acetaldehyde concentrations were detected after glucose infusion in the gastric juice of four atrophic gastritis patients. After ethanol infusion, the mean intragastric acetaldehyde level of the atrophic gastritis patients was 4.5-fold at 30 min and 6.5-fold at 60 min compared to controls. In vitro, the difference between the study groups was even higher, 7.6-fold. A vast selection of oral bacterial species and some Enterobacteriaceae and yeasts were presented in the gastric juice of atrophic gastritis patients. CONCLUSIONS: Microbial ethanol metabolism leads to high intragastric acetaldehyde levels after ethanol drinking in achlorhydric atrophic gastritis patients. This could be one of the factors responsible for enhanced gastric cancer risk among atrophic gastritis patients.     

Gastric Factors Influencing Iron Absorption in Anaemic Patients

The absorption of a tracer dose of ferric citrate given to normal human subjects together with a meal was not increased when gastric juice from an anaemic patient was given simultaneously. The increase in iron absorption which occurs in achlorhydric anaemic patients when gastric juice from another anaemic patient is given appears to be due to the acid content of the gastric juice. These findings do not support the hypothesis that there is a substance in gastric juice other than acid which influences iron absorption.     

Gastric acid barrier to ingested microorganisms in man: studies in vivo and in vitro

Reassessment of the ;gastric bactericidal barrier' to enteric bacteria in man included studies of the bactericidal activity of (1) the normal and achlorhydric stomach in vivo and (2) normal and achlorhydric gastric juice and other media in vitro. Within 30 minutes virtually all bacteria (Serratia marcescens) were eliminated in the normal stomach whereas no reduction occurred in the achlorhydric stomach in one hour. In vitro, identical bactericidal activity was observed at the same pH (from 2.0 to 7.0) in normal gastric juice, achlorhydric gastric juice, aqueous HCl, and nutrient broth. At pH less than 4.0, 99.9% of the bacteria were killed within 30 minutes. The presence of profuse bacterial flora, including coliforms, found in markedly acid-deficient but not in normal stomachs, correlates well with the absence of bactericidal activity. Thus, the ;gastric bactericidal barrier' is primarily pH-hydrochloric acid dependent, with other constituents of gastric juice contributing little, if any, detectable effect on the destruction of microorganisms.     

Intestinal bacterial flora and bile salt studies in hypogammaglobulinaemia

Five patients with adult acquired hypogammaglobulinaemia, four of whom were achlorhydric, were studied. Jejunal bacterial counts were much higher than those in a control group of acid secretors, but were similar to those in a control group of patients with pernicious anaemia; Giardia lamblia were isolated from the jejunal content of all patients with hypogammaglobulinaemia. The concentration of conjugated bile acids in the fasting state was lower in hypogammaglobulinaemia than in pernicious anaemia, but in the two hypogammaglobulinaemic patients with steatorrhoea there was a normal bile salt response to a fatty meal.     

Nonantral Gastric Carcinoid Tumours Associated with Hypergastrinaemia

ABSTRACT. Nonantral gastric carcinoid tumours in association with pronounced hypergastrinaemia are reported in 6 patients. It is suggested that the hypergastrinaemia, as a result of lack of a negative acid feedback inhibition in an achlorhydric stomach, promoted the tumour development, possibly initiated by action of carcinogenic nitrosamines, in the gastric juice.     

Comparison of gastrointestinal loss of alpha-1-antitrypsin and chromium-51-albumin in Ménétrier's disease and the influence of ranitidine

In a 37-year-old patient with Ménétrier's disease, 51Cr-albumin and alpha 1-antitrypsin (alpha 1-AT) output was measured simultaneously in gastric juice and feces. While the 51Cr-albumin studies demonstrated a threefold increase in gastrointestinal protein loss, alpha 1-AT was found in normal quantities in gastric juice and feces. The histamine H2 antagonist, ranitidine, led to a marked reduction in gastric protein loss, as evidenced by decreased 51Cr activity in the stomach. Studies of protein loss in the gastric juice during pentagastrin stimulation (6 micrograms/kg/h) showed that the 51Cr-albumin output paralleled the volume secreted, whereas alpha 1-AT decreased with lower pH values, not being detectable below pH 3. This probably results from peptic degradation of alpha 1-AT at low pH. We conclude that fecal alpha 1-AT determination cannot be used for the assessment of protein-losing gastropathy in patients who are not achlorhydric.     

Composition of the alkaline component of human gastric juice: effect of swallowed saliva and duodeno-gastric reflux.

Five patients (four with vitiligo and one with pernicious anaemia) were subjected to the histamine infusion test; there were achlorhydric while the remaining two secreted quite small amounts of acid. [Na+],[Cl-)and[alkali]were determined in the alkaline gastric juice samples (pH greater than 7.0). In order to assess the contribution of swallowed saliva the histamine test was done twice in each patient: (A) with precautions to prevent swallowing of saliva; and (B) with the patient allowed to swallow saliva freely. In each sample reflux of duodenal juice was estimated so that its contribution to the alkaline gastric aspirate could be assessed. Such reflex was absent in one patient, negligible in another, while in the remaining three patients the mean pyloric reflux amounted to no more than 8% of the observed volume. Swallowed saliva had diluting effect on [Na+] and [Cl-] but raised K+ concentration in the alkaline gastric aspirate. The comparison of alkaline gastric juice, free to an appreciable extent of salivary contamination, was shown to be relatively constant. The results are consistent with the two-component hypothesis of gastric secretion.     

The value of the hydrogen (H2) breath test for the diagnosis of bacterial overgrowth in gastric achlorhydria

Sixteen healthy volunteers, 23 patients with peptic disease, and 38 patients with achlorhydria were investigated with bacterial cultures from gastric juice and a hydrogen (H2) breath test after a standard meal. In acid-secreting subjects upper respiratory tract bacteria were found in 6/39. In every single achlorhydric patient gastric bacterial concentrations were above log 10 5.7/ml. Fecal flora was found in 22/38. The patient with fecal organisms were significantly older than those without (p less than 0.05). The H2 breath test revealed low postprandial carbohydrate fermentation in acid secretors and in achlorhydrics with no fecal flora. The lowest H2 production was found 90 and 120 min after the meal. In achlorhydrics with fecal organisms the mean H2 concentration at these times of measurement was elevated (p less than 0.05). Assuming that a mean H2 concentration at 90 and 120 min above 19 ppm (mean in healthy volunteers at 90 and 120 min + 2 SD) is pathological, the association of fecal bacteria in gastric juice and a "positive" H2 breath test is highly significant (P less than 0.001). Fecal bacteria in the gastric juice would indicate small-intestinal fermentation with a probability of 81%. A gastric culture negative for fecal organisms would predict a "negative" H2 breath test with a probability of 91%.     

Mt 21-42: development and validation of an automatic device proposed for the endoscopic diagnosis of Helicobacter pylori infection and atrophic gastritis

BACKGROUND: Gastric juice may give important clinico-pathological information, but measurements in this medium are difficult. In this study we present and validate an innovative device (Mt 21-42) performing gastric juice analyses during endoscopy and proposed for the endoscopic diagnosis of Helicobacter pylori infection and hypo/achlorhydria. METHODS: Analyses on both aqueous solutions (80 pH buffer + 120 ammonium chloride samples) and human gastric juice were carried out to assess the measuring performance of Mt 21-42 on the ideal and real matrix, respectively. Matrix spike and manipulation tests were also performed to investigate the matrix effect of gastric juice and to evaluate the consequences of its manipulation on the measurements. Furthermore, preliminary clinical tests were performed to evaluate the clinical potentiality of the device. RESULTS: Mt 21-42 showed a good measuring performance on ideal matrix (coefficient variation: pH = 1.3%, ammonium = 2.1%) and real matrix (coefficient variation: pH = 1.2%, ammonium = 1.9%). Analyses on gastric juice excluded a substantial matrix effect (percent recovery =96.5-98.7%) but demonstrated a significant influence of manipulation procedures (p < 0.05). CONCLUSIONS: Human gastric juice does not have a substantial matrix effect for pH and ammonium determination, but its manipulation may affect the measurement of these components. Mt 21-42 represents a precise instrument for the measurement of gastric juice and a potential precious tool for the endoscopic detection of H. pylori infection and hypo/achlorhydric conditions.     

Histological analysis of the gastric mucosa, enterochromaffin cells and gastrin-producing cells in endoscopic biopsies of patients with achlorhydria

Twenty achlorhydric patients and five controls were submitted to gastric endoscopic biopsies in order to study the histological pattern of the gastric mucosa and the number of enterochromaffin (EC) and gastrin (G) cells of the antral mucosa. The histological changes of the oxyntic mucosa of achlorhydric patients were variable being the predominant pattern the severe chronic atrophic gastritis. The antral mucosa was normal in appearance or revealed mild degree of gastritis. In the most achlorhydric patients the antral EC cell number was decreased when compared to the controls and the G cell number were relatively numerous. The results of the present work are suggestive of an increased G:EC cell ratio in achlorhydric patients.     

Gastric juice in pernicious anemia

Summary The physicochemical composition of the gastric juice of 16 patients suffering from pernicious anemia was determined. The study of the relationship between chloride, sodium, and alkalinity showed that gastric juice in these patients has the same characteristics as the primary alkaline secretion of a patient with a normal stomach. The stomach of a patient with Biermer's disease, from the biologic point of view, appears to be one that has been deprived of its acid (parietal cells) and peptic (chief cells) functions and, on the other hand, has retained normal glands of alkaline secretion.The values of primary alkaline secretion determined in the study reported here seem to be more realistic than those obtained mathematically by Hollander, Gray and Butcher, in dogs, and Hunt, in humans.A better knowledge of the composition of the primary alkaline secretion makes possible—without recourse to measurement of thepH or administration of large doses of histamine, which are not always tolerated in spite of the use of antihistaminics—a simple distinction between absolute achlorhydria of cellular origin, which is characteristic of Biermer's disease, and relative or chemical achlorhydria, which disappears under the influence of certain drugs that increase the concentration of acid in the gastric juice (corticoids or larger doses of histamine). In patients having so-called achlorhydric gastric juice, the two types may be distinguished, according to Töpfer, by determination of the total alkalinity of the samples taken during intubation in stages. An alkalinity curve that does not change after injection of the usual dose of histamine dihydrochloride (0.5 mg.) indicates true achlorhydria of the Biermer type, and an alkalinity curve that reflects declining values signifies chemical achlorhydria.Cellular achlorhydrias are very rare other than in Biermer's disease; of a total of 73 patients with achlorhydrias without anemia, the authors observed 5 cases, 3 associated with cirrhosis with ascites and 2, in the course of early gastritis.     

Reducing carcinogenic acetaldehyde exposure in the achlorhydric stomach with cysteine

Background: Acetaldehyde, associated with alcohol consumption, has recently been classified as a group 1 carcinogen in humans. Achlorhydric atrophic gastritis is a well‐known risk factor for gastric cancer. Achlorhydria leads to microbial colonization of the stomach. Several of these microbes are able to produce significant amounts of acetaldehyde by oxidation from alcohol. Acetaldehyde can be eliminated from saliva after alcohol intake and during smoking with a semi‐essential amino acid, l‐ cysteine. The aim of this study was to determine whether cysteine can be used to bind acetaldehyde in the achlorhydric stomach after ethanol ingestion. Methods: Seven volunteers with achlorhydric atrophic gastritis were given either slow‐release l‐ cysteine or placebo capsules in a double‐blinded randomized trial. Volunteers served as their own controls. A naso‐gastric tube was inserted to each volunteer. The volunteers ingested placebo or 200 mg of l‐ cysteine capsules, and ethanol 0.3 g/kg body weight (15 vol%) was infused intragastrically through a naso‐gastric tube. Five‐milliliter samples of gastric contents were aspirated at 5‐minute intervals. Results: During the follow‐up period, the mean acetaldehyde level of gastric juice was 2.6 times higher with placebo than with l‐ cysteine (13 vs. 4.7 μM, p < 0.05, n = 7). Conclusions: l‐ cysteine can be used to decrease acetaldehyde concentration in the achlorhydric stomach during alcohol exposure. Intervention studies with l‐ cysteine are needed on reducing acetaldehyde exposure in this important risk group for gastric cancer.     

Effect of eradication of Helicobacter pylori on gastric juice ascorbic acid concentrations.

Ascorbic acid, the reduced form of vitamin C, may protect against gastric cancer and is secreted by the normal stomach. Secretion is impaired in Helicobacter pylori (H pylori) associated chronic gastritis. This study examined if eradication of H pylori improves gastric juice ascorbate values. Fasting gastric juice and plasma samples were collected at endoscopy from patients participating in trials of H pylori eradication for duodenal ulcer disease and intestinal metaplasia before and up to 15 months after attempted eradication. Ascorbic acid and total vitamin C concentrations were determined by high performance liquid chromatography. In 12 patients in whom H pylori was successfully eradicated gastric juice ascorbate and total vitamin C concentrations and the ratio of juice to plasma vitamin C rose after treatment. Analysis after treatment suggested that the rise was greatest in patients with high final plasma vitamin C concentrations, even though these did not change with treatment. By contrast, in 22 patients in whom H pylori eradication was unsuccessful there were no significant changes in juice or plasma concentrations after treatment. It is concluded that successful eradication of H pylori improves secretion of vitamin C into gastric juice. It is speculated that this increases protection against gastric cancer.     

Hydrogen (H2) breath test and gastric bacteria in acid-secreting subjects and in achlorhydric and postgastrectomy patients before and after antimicrobial treatment

Sixteen patients with pentagastrin-fast achlorhydria and 12 patients who had undergone Billroth II gastrectomy (at least 3 years previously) were compared with 10 acid-secreting volunteers and 13 patients with endoscopically proven peptic disease. The concentration and type of gastric bacteria were analysed in achlorhydrics, Billroth II patients, and patients with peptic disease. A 6-h hydrogen (H2) breath test after a standardized meal was performed in all subjects. The mean concentration of gastric bacteria was significantly higher in achlorhydrics and Billroth II patients than in patients with peptic disease. End-expiratory H2 excretion was elevated in achlorhydrics and Billroth II patients to levels significantly exceeding those of acid-secreting volunteers and patients with peptic disease. In achlorhydrics, total bacterial concentration in gastric juice was correlated to H2 excretion between 60 and 180 min after the meal. Treatment of achlorhydric and postgastrectomy patients with trimethoprim/sulphamethoxazole lowered H2 breath concentrations in both groups and reduced symptoms in achlorhydrics. Elevated end-expiratory H2 levels after a test meal indicate upper gastrointestinal bacterial overgrowth in achlorhydrics and in postgastrectomy patients.     

Gastric juice nitrite and vitamin C in patients with gastric cancer and atrophic gastritis: is low acidity solely responsible for cancer risk?

BACKGROUND: N-nitroso compounds are carcinogens formed from nitrite, a process that is inhibited by vitamin C in gastric juice. Helicobacter pylori infection has been reported to increase nitrite and decrease vitamin C in gastric juice. Therefore, susceptibility to gastric cancer in H. pylori-infected patients may be derived from increased N-nitroso compounds in gastric juice. However, most H. pylori-infected patients do not develop gastric cancer. OBJECTIVE: To investigate additional factors that may affect susceptibility to gastric cancer, we compared nitrite and vitamin C levels in gastric juice from H. pylori-infected patients with and without gastric cancer. METHODS: Serum and gastric juice were obtained from 95 patients undergoing diagnostic endoscopy, including those with normal findings, duodenal ulcer, gastric ulcer, atrophic gastritis and gastric cancer. Serum was analysed for H. pylori antibody, nitrate and nitrite, gastrin and pepsinogens; gastric juice was analysed for pH, nitrite and vitamin C. RESULTS: pH and nitrite levels were increased and vitamin C levels decreased in the gastric juice of patients with atrophic gastritis and gastric cancer compared with other patients. However, in patients with a similar gastric acidity (pH 5-8), nitrite concentrations in the gastric juice were significantly higher and vitamin C levels significantly lower in patients with gastric cancer than in those with atrophic gastritis. CONCLUSION: Although hypochlorhydria increases intraluminal nitrite and decreases intraluminal vitamin C, which increases the intraluminal formation of N-nitroso compounds, our results indicate that patients with gastric cancer may have additional factors that emphasize these changes.     

Antral Gastrin Cells and Serum Gastrin in Achlorhydria

Forty-five patients with achlorhydria due to severe atrophic corpus gastritis or gastric atrophy were studied by determination of serum gastrin, histological examination of multiple biopsy specimens from the antrum, and quantitation of gastrin cells revealed by an indirect immunofluorescence technique. In a reference group of 12 persons with normal gastric secretion and without atrophic antral gastritis, the mean number of gastrin cells per field of vision was 52±6.5 (S.E.M.). In a group of achlorhydric patients having normal antral mucosa (n = 24), the serum gastrin level was 324±56 pmol/1 and the number of gastrin cells was 79.6±7.5 cells/field of vision. The corresponding values for a group of achlorhydric patients with chronic superficial antral gastritis (n = 11) were 361±186 pmol/1 and 88.0±14.4 cells/field of vision. In a group of achlorhydric patients with atrophic antral gastritis (n = 10) serum gastrin was 15.0±3.3 pmol/1, and the number of gastrin cells was 6.2±3.3 cells/field of vision. Compared to the subjects in the reference group, the number of gastrin cells was significantly higher in the groups of achlorhydric patients with normal or superficially inflamed antral mucosa and significantly lower in achlorhydric patients with atrophic antral gastritis. It is concluded that serum gastrin in general is a good indicator for the presence or absence of antral atrophic gastritis in achlorhydria.     

Antral gastrin cells and serum gastrin in achlorhydria.

Forty-five patients with achlorhydria due to severe atrophic corpus gastritis or gastric atrophy were studied by determination of serum gastrin, histological examination of multiple biopsy from the antrum, and quantitation of gastrin cells revealed by an indirect immunofluorescence technique. In a reference group of 12 persons with normal gastric secretion and without atrophic antral gastritis the mean number of gastrin cells per field of vision was 52 +/- 6.5 (S.E.M.). In a group of achlorhydric patients having normal antral mucosa (n = 24), the serum gastrin levels was 324 +/- 56 pmol/l and the number of gastrin cells was 79.6 +/- 7.5 cells/field of vision. The corresponding values for a group of achlorhydric patients with chronic superficial antral gastritis (n = 11) were 361 +/- 186 pmol/l and 88.0 +/- 14.4 cells/field of vision. In a group of achlorhydric patients with atrophic antral gastritis (n = 10) serum gastrin was 15.0 +/- 3.3 pmol/l, and the number of gastrin cells was 6.2 +/- 3.3 cells/field of vision. Compared to the subjects in the reference group, the number of gastrin cells was significantly higher in the groups of achlorhydric patients with normal or superficially inflamed antral mucosa and significantly lower in achlorhydric patients with atrophic antral gastritis. It is concluded that serum gastrin in general is a good indicator for the presence or absence of antral atrophic gastritis in achlorhydria.     

The role of histamine and serotonin in gastric acid secretion: A comparative study in gastric and duodenal ulcer patients

The inter-relationship between histamine and serotonin (5HT) levels in gastric juice and their role in stomach acid secretion in gastric (GU) and duodenal ulcer (DU) patients were investigated. DU patients showed a relatively higher basal gastric acid secretion, but had lower histamine and 5HT levels in their gastric juice than those with GU; these amine levels reflected their release from the stomach wall into its lumen. Tetragastrin injection (5 μg/kg, i.m.) increased the gastric secretion of acid and histamine in DU patients; however, the increased release of 5HT into the gastric lumen was not as much as that seen in GU patients. This study suggests that the high basal gastric acid in DU cases is related to hyposecretion of 5HT (a possible physiological inhibitor of gastric acid secretion) in the stomach. Tetragastrin-induced hypersecretion of gastric acid in DU patients may be due to a higher level of histamine in relation to significantly lower amounts of 5HT secreted from their stomachs. The reverse may apply to the mechanism for the relative hyposecretion of gastric acid in GU patients compared to those with DU.     

Effect of Helicobacter pylori and its eradication on gastric juice ascorbic acid.

The presence of ascorbic acid in gastric juice may protect against gastric carcinoma and peptic ulceration. This study examined the effect of Helicobacter pylori (H pylori) on the secretion of ascorbic acid into gastric juice by measuring fasting plasma and gastric juice ascorbic acid concentrations in patients with and without the infection and also before and after its eradication. Gastric juice ascorbic acid concentrations in 19 H pylori positive patients were significantly lower (median 2.8, range 0-28.8 micrograms/ml) than those in 10 H pylori negative controls (median 17.8, range 5.6-155.4 micrograms/ml) (p < 0.0005) despite similar plasma ascorbic acid concentrations in both groups. The median gastric juice:plasma ascorbic acid ratio in the H pylori positive patients was only 1.16 (range 0.02-6.67), compared with a median ratio of 4.87 (range 0.76-21.33) in H pylori negative controls (p < 0.01). In the patients with H pylori infection there was a significant negative correlation between the severity of the antral polymorphonuclear infiltrate and gastric juice ascorbic acid concentrations (correlation coefficient -0.52, p = 0.02). After eradication of H pylori in 11 patients, gastric juice ascorbic acid concentrations rose from 2.4 (0-12.8 micrograms/ml) to 11.2 (0-50 micrograms/ml) (p = 0.01). The median gastric juice: plasma ascorbic acid ratio also increased from 1.33 (0.05-6.67) to 2.89 (0.01-166) (p = 0.01). In conclusion, the high gastric juice:plasma ascorbic acid ratio in H pylori negative subjects shows active secretion of ascorbic acid into gastric juice. Secondly, H pylori infection causes a reversible lowering of gastric juice ascorbic acid concentrations, which may predispose to gastric carcinoma and peptic ulceration.