Gastric Bile Acid Research Articles

No Long-Term Mucosal Lesions in the Esophagus but More Gastric Mucosal Lesions after Sleeve Gastrectomy in Obese Rats

Sleeve gastrectomy (SG) often induces gastroesophageal reflux, with few and discordant long-term data on the risk of Barrett's esophagus (BE) in operated patients. The aim of this study was to analyze the impact of SG on esogastric mucosa in a rat model at 24 weeks postoperatively, which corresponds to approximately 18 years in humans. After 3 months of a high-fat diet, obese male Wistar rats were subjected to SG (n = 7) or sham surgery (n = 9). Esophageal and gastric bile acid (BA) concentrations were measured at sacrifice, at 24 weeks postoperatively. Esophageal and gastric tissues were analyzed by routine histology. The esophageal mucosa of the SG rats (n = 6) was not significantly different in comparison to that of the sham rats (n = 8), with no esophagitis or BE. However, there was more antral and fundic foveolar hyperplasia in the mucosa of the residual stomach 24 weeks after SG than in the sham group (p < 0.001). Luminal esogastric BA concentrations did not differ between the two groups. In our study, SG induced gastric foveolar hyperplasia but no esophageal lesions at 24 weeks postoperatively in obese rats. Therefore, long-term endoscopic esophageal follow-up that is recommended in humans after SG to detect BE may also be useful for detecting gastric lesions.

Deoxycholic acid induces gastric intestinal metaplasia by activating STAT3 signaling and disturbing gastric bile acids metabolism and microbiota

ABSTRACT Intestinal metaplasia (IM) is the inevitable precancerous stage to develop intestinal-type gastric cancer (GC). Deoxycholic acid (DCA) is the main bile acid (BA) component of duodenogastric reflux and has shown an increased concentration during the transition from chronic gastritis to IM associated with continued STAT3 activation. However, the mechanisms underlying how DCA facilitates IM in the gastric epithelium need exploration. We evaluated IM and bile reflux in corpus tissues from 161 subjects undergoing GC screening. Cell survival and proliferation, proinflammatory cytokine expression and TGR5/STAT3/KLF5 axis activity were measured in normal human gastric cells, cancer cells, and organoid lines derived from C57BL/6, FVB/N and insulin-gastrin (INS-GAS) mice treated with DCA. The effects of DCA on IM development were determined in INS-GAS mice with long-term DCA supplementation, after which the gastric bacterial and BA metabolic profiles were measured by 16S rRNA gene sequencing and LC-MS. We revealed a BA-triggered TGR5/STAT3/KLF5 pathway in human gastric IM tissues. In gastric epithelial cells, DCA promoted proliferation and apoptotic resistance, upregulated proinflammatory cytokines and IM markers, and facilitated STAT3 phosphorylation, nuclear accumulation and DNA binding to the KLF5 promoter. DCA triggered STAT3 signaling and the downstream IM marker KLF5 in mouse gastric organoids in vitro and in vivo. In INS-GAS mice, DCA promoted the accumulation of serum total BAs and accelerated the stepwise development of gastric IM and dysplasia. DCA induced gastric environmental alterations involving abnormal BA metabolism and microbial dysbiosis, in which the Gemmobacter and Lactobacillus genera were specifically enriched. Lactobacillus genus enrichment was positively correlated with increased levels of GCA, CA, T-α-MCA, TCA and β-MCA in DCA-administrated INS-GAS mice. DCA promotes nuclear STAT3 phosphorylation, which mediates KLF5 upregulation associated with gastric inflammation and IM development. DCA disturbs the gastric microbiome and BA metabolism homeostasis during IM induction.

The Spatial Landscape of the Bacterial Community and Bile Acids in the Digestive Tract of Patients With Bile Reflux.

BackgroundBile reflux can lead to inflammation and increased intestinal metaplasia. Since bile acids can influence the gastrointestinal environment, it is possible that bile reflux may alter the gastric microbiota and potentially the oral or gut microbiota. Bile acids have a very complex interrelationship with microbiota. We aimed to explore the characteristics of the digestive tract microbiota and bile acids profile in bile reflux patients.MethodsThis study included 20 chronic gastritis patients with bile reflux and 20 chronic gastritis patients without bile reflux. Saliva, gastric fluid, and fecal samples were collected for bile acid testing. Buccal mucosal swabs, gastric mucosal tissues, and feces were collected for bacteria detection. The UPLC-MS/MS examined bile acids profiles. 16S rRNA gene sequencing was used to analyze the bacterial profile.ResultsBilirubin in the blood increased in bile reflux patients. No other clinical factors were identified to be significantly associated with bile reflux. 12-DHCA, 6,7-diketo LCA, and βHDCA decreased while TUDCA increased in saliva of bile reflux patients. Streptococcus, Capnocytophaga, Neisseria, and Actinobacillus decreased in oral mucosa of bile reflux patients while Helicobacter, Prevotella, and Veillonella increased. Gastric bile acid levels were generally higher in bile reflux patients. Gastric mucosal microbiota was highly stable. The changes in fecal bile acids were insignificant. Bifidobacterium, Prevotella_2, Ruminococcus, Weissella, Neisseria, and Akkermansia decreased in fecal samples from bile reflux patients; while Alloprevotella, Prevotella_9, Parabacteroides, and Megamonas increased.ConclusionOur results demonstrate that bile reflux significantly alters the oral, gastric, and intestinal bile acids profiles but only influences the oral and gut microbiota composition. These findings indicate that bile reflux can modulate the gastrointestinal microbiota in a site-specific manner.

Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer.

Bile acids have been linked to pathomechanism and prognosis in various types of cancers. The present study aimed to investigate the effect of bile acids on the molecular change in gastric epithelial cancer cells and to evaluate gastric bile acid concentration in patients with early gastric cancer (EGC). Human gastric cancer cells (AGS and NCI-N87 cell lines) were treated with several bile acid types to determine their effect on molecular changes in the cells. Gastric levels of individual bile acids were measured (primary unconjugated or conjugated bile acids and secondary bile acids) in 39 participants (20 controls and 19 patients with EGC). Exposing gastric epithelial cancer cells to primary bile acids in vitro upregulated the expression of early growth response factor 1 (Egr-1) and the oncogenes including c-Jun, c-Myc and Snail, whereas a p42/44 MAPK inhibitor exposure reduced their expression. There was a significant difference in age and presence of atrophic gastritis with intestinal metaplasia in background mucosa between controls and patients with EGC. There were significant differences in the levels of unconjugated or conjugated primary bile acids between controls and EGC patients except lithocholic acid. After adjustment of age and presence of atrophic gastritis with intestinal metaplasia, the levels of cholic acid [adjusted odds ratio (aOR) 4.3; 95% confidence interval (CI): 1.2-16.2; P=0.029] and glycochenodeoxycholic acid [aOR 9.9; 95% CI: 1.3-75.3; P=0.027] were significantly higher in patients with EGC compared with controls. In conclusion, bile acids upregulate Egr-1 in gastric cancer cells via the MAPK signaling pathway, and higher gastric levels of primary bile acids are associated with EGC. Therefore, exposure of gastric cells to primary bile acids may play a role in gastric carcinogenesis.

In vitro tesztrendszer alkalmazása probiotikus baktériumtörzsek szelektálására

The aim of our studies was to evaluate in vitro methods for the simple and efficient selection of putative probiotic bacterial strains. Of the possible methods, the following were tested: culturing on selective media, Gram staining, catalase assay, hemolytic, clonality and aggregation ability, gastric acid tolerance and bile acid tolerance. A total of 217 bacterial strains isolated from raw sheep’s milk, curdled milk and sheep’s cheese samples produced in Transylvania were included in our experiments. Isolates with hemolytic activity, as well as those exhibiting Gram-negative or catalase-positive phenotypes not characteristic of probiotics were excluded from our studies. Based on the results of RAPD-PCR studies suitable for the detection of individual-level polymorphisms, a total of 34 clone classes and 57 strains with unique RAPD patterns were identified. From each of the 34 clone classes thus narrowed, one strain was selected and tested for its aggregation ability, as well as its gastric acid and bile acid tolerance. High aggregation values above 70%, typical of probiotic strains, were measured in the case of a total of six isolates. In the course of the presence-absence studies conducted on the surface of solid media supplemented with acid or bile acid, it was possible to select several strains specifically tolerant to acid or bile acid. Based on our results, isolates to be included in further tests, e.g., in antibiotic resistance and antimicrobial activity assays, were selected.

Risk Factors for Bile Aspiration and its Impact on Clinical Outcomes.

INTRODUCTION:Bile reflux may cause for lung allograft rejection, yet there are no studies that determine (i) the relationship between gastric and lung bile concentrations, (ii) whether bile is present in lungs of nontransplant patients, (iii) the relationship between gastric dysmotility and lung bile, (iv) the impact of reflux therapies on lung bile, and (v) whether lung bile worsens outcomes in nontransplant patients. This study will address these gaps in the literature.METHODS:We prospectively recruited lung transplant (LTX) patients and nontransplant patients with respiratory symptoms (RP) and collected paired gastric and lung samples. Bile concentration and composition of samples was assessed using liquid chromatography–mass spectrometry. Bile results were compared with clinical parameters, including the presence of esophagitis, gastric dysmotility, and/or pathologic gastroesophageal reflux.RESULTS:Seventy patients (48 RP and 22 LTX) were recruited. Overall, 100% of gastric and 98% of bronchoalveolar lavage samples contained bile. The mean gastric bile concentrations in RP and LTX patients were 280 ± 703 nmol/L and 1,004 ± 1721 nmol/L, respectively (P = 0.02). There was no difference in lung bile concentrations between RP (9 ± 30 nmol/L) and LTX (11 ± 15 nmol/L, P = 0.7). Patients with delayed gastric emptying had higher lung bile concentrations (15.5 ± 18.8 nmol/L) than patients with normal gastric emptying (4.8 ± 5.7 nmol/L, P = 0.05) independently of reflux burden. Proton pump inhibitor use increased the proportion of unconjugated gastric bile acids. High lung bile concentrations were associated with an increased risk of hospitalization and longer hospital stays in RP patients (P < 0.05).DISCUSSION:Lung bile is almost universally present in symptomatic patients, and higher concentrations are associated with poorer respiratory outcomes.

Increased levels of conjugated bile acids are associated with human bile reflux gastritis

Bile acids (BAs) play essential roles in facilitating lipid digestion and absorption in the intestine. Gastric BAs were attributed to abnormal refluxing from duodenal compartments and correlated with the occurrence of gastric inflammation and carcinogenesis. However, the differences in gastric BAs between physiologically compromised and healthy individuals have not been fully investigated. In this study, gastric juice was collected from patients clinically diagnosed as gastritis with/without bile reflux and healthy subjects for BA profiles measurements. As a result, we found that the conjugated BAs became prominent components in bile reflux juice, whereas almost equal amounts of conjugated and unconjugated BAs existed in non-bile reflux and healthy juice. To investigate whether gastric BA changes were regulated by hepatic BA synthesis, C57BL/6J mice were intervened with GW4064/resin to decrease/increase hepatic BA synthesis. The results revealed that changes of gastric BAs were coordinated with hepatic BA changes. Additionally, gastric BAs were detected in several healthy mammals, in which there were no obvious differences between the conjugated and unconjugated BAs. Pigs were an exception. Thus, increased levels of conjugated BAs are associated with human bile reflux gastritis. Gastric conjugated BAs could become a panel of biomarkers to facilitate diagnosis of pathological bile reflux.

Long-term consequences of one anastomosis gastric bypass on esogastric mucosa in a preclinical rat model

Although bariatric surgery is proven to sustain weight loss in morbidly obese patients, long-term adverse effects have yet to be fully characterized. This study compared the long-term consequences of two common forms of bariatric surgery: one-anastomosis gastric bypass (OAGB) and Roux-en-Y Gastric Bypass (RYGB) in a preclinical rat model. We evaluated the influence of biliopancreatic limb (BPL) length, malabsorption, and bile acid (BA) reflux on esogastric mucosa. After 30 weeks of follow-up, Wistar rats operated on RYGB, OAGB with a short BPL (15 cm, OAGB-15), or a long BPL (35 cm, OAGB-35), and unoperated rats exhibit no cases of esogastric cancer, metaplasia, dysplasia, or Barrett’s esophagus. Compared to RYGB, OAGB-35 rats presented higher rate of esophagitis, fundic gastritis and perianastomotic foveolar hyperplasia. OAGB-35 rats also revealed the greatest weight loss and malabsorption. On the contrary, BA concentrations were the highest in the residual gastric pouch of OAGB-15 rats. Yet, no association could be established between the esogastric lesions and malabsorption, weight loss, or gastric bile acid concentrations. In conclusion, RYGB results in a better long-term outcome than OAGB, as chronic signs of biliary reflux or reactional gastritis were reported post-OAGB even after reducing the BPL length in a preclinical rat model.

Gastric Residual to Predict Necrotizing Enterocolitis in Preterm Piglets As Models for Infants.

Necrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease in preterm infants. High volume of gastric residual (GR) after oral feedings is often used as a predictor of NEC, but evidence is limited. Using NEC-sensitive preterm piglets as models, we hypothesized that GR mass and related plasma biomarkers predict early onset of NEC. In total, 258 newborn preterm piglets were fed bovine milk-based formulas for 5 days. At euthanasia, the stomach, small intestine, and colon were evaluated for NEC lesions. Mass, acidity, gastrin, and bile acid levels were determined for GR content, together with gastrin, glucagon-like peptide 2 (GLP-2), and gastric inhibitory polypeptide (GIP) levels in plasma. In total, 48% of piglets had NEC lesions in the small intestine and/or colon. These piglets had higher GR mass (+32%, P < 0.001) and lower gastric bile acid concentrations (-22%, P < 0.05) than piglets without NEC lesions. The positive and negative predictive values for these markers were 34%-61%. Gastric acidity, gastrin, GLP-2, and GIP levels were similar for piglets with and without NEC lesions. Elevated GR mass correlates positively with NEC lesions but may be a poor predictor of NEC, even when combined with other biomarkers. More knowledge about gastric emptying and gut transit in preterm neonates is required to understand how GR volume and composition relate to morbidities, such as NEC, in preterm neonates.

Development of lyophilization procedure ensuring survival of bifidobacteria and preservation of their probiotic potential upon long-term storage

Survival of bifidobacteria and preservation of their morphological characteristics after 12-month storage of lyophilized cells was studied for the strains of Bifidobacterium bifidum and B. animalis isolated and maintained in the microbial collection of the Department of Microbiology, Moscow State University. A combined approach to pre-lyophilization treatment of microorganisms and subsequent storage was developed in order to improve cell survival. Compared to the standard cryoprotector concentrations, sucrose and glucose (5% and higher) in skim milk, as well as freezing at ‒70°C with subsequent storage at the same temperature resulted in improved survival of bifidobacteria. Under such conditions, the number of viable cells (CFU) after 12 months of storage was two to three orders of magnitude higher than in the case of the standard lyophilization procedure. Investigation of dynamics of resistance of reactivated clones to such gastrointestinal stress factors as gastric juice and bile acids revealed preservation of these properties at all storage modes. However, since the number of surviving cells decreased during storage according to the standard procedure, the number of stress-affected cells was correspondingly lower. Reactivated cultures exhibited high resistance to oxygen, with survival decreasing to 35% of the initial level.

Immunomodulatory and Antigenotoxic Properties of Bacillus amyloliquefaciens KU801

The Bacillus KU801 strain, due to its potential in the field of probiotics for animal use, was isolated from chicken feces. Strain KU801 was identified as Bacillus amyloliquefaciens KU801 based on the results of 16S rRNA sequencing. Vegetative and spore cells of B. amyloliquefaciens KU801 were resistant to artificial gastric juice and artificial bile acid. B. amyloliquefaciens KU801 was found to inhibit the production of nitric oxide (NO) and increase the production of Interleukin-1 alpha (IL-1). DNA damage induced by N-methyl-Ntion of ninitroso-guanidine (MNNG) was significantly inhibited, in a dose dependent manner, by preincubating MNNG together with B. amyloliquefaciens KU801. These results demonstrate the potential use of B. amyloliquefaciens KU801 as a feed additive.

Encapsulation of &lt;i&gt;Bifidobacterium bifidum&lt;/i&gt; in Improved Alginate Microcapsules to Prolonging Viability

Bifidobacterium bifidum were encapsulated as fresh cultures in water insoluble food grade microcapsules by emulsification–internal gelation technique, using gelatin, pectin, alginate and chitose as immobilization material. The optical photomicroscope photograph and laser scanning confocal microscope photograph shows that the microcapsules obtained by this method has narrow size distribution (10-20 μm). Survival of Bifidobacterium bifidum in microcapsules was 109cfu•g-1 , and the embedding ratio was 72.32%. The survival was remaining more than 108cfu•g-1 after exposure to gastric acid and bile acid, which implies that the microcapsules expressed superior acid resistance. These microcaosules were disaggregation subtotal after 15 min in simulated intestinal juices, and the release rate was 96%. The survival was 108 cfu•g-1 at room temperature after 1 year by classic accelerated test. The results indicate that encapsulation of Bifidobacterium bifidum in alginate microcapsules is a good approach to prolonging viability.

Abstract 4105: Nitric-oxide-mediated inhibition of Na+/H+ exchange (NHE) is a novel mechanism of bile acid induced damage: Relevance to esophageal carcinogenesis

Abstract Background: Barrett's esophagus (BE) is a premalignant condition that is associated with gastroesophageal reflux disease (GERD). Gastric acid and bile acids are two components of refluxate that induce proliferation, DNA damage and oxidative stress. In combination, the effects of gastric acid and bile acids are amplified and synergistic. The major goal of this study was to evaluate the effect of bile acids alone or in combination with acid on intracellular pH (pHi). A mechanism responsible for bile acid-induced pHi alterations was examined. Methods: CP-A cells (non-dysplastic Barrett's esophagus cells) were treated with medium acidified to pH 5.5 and/or 0.5mM bile acid cocktail in the presence/absence of inhibitors of nitric oxide synthase (NOS) or NHE (sodium-hydrogen exchanger). pHi was measured by BCECF microfluorimetry in perfused cells, nitric oxide by DAF-FM fluorescence and DNA damage by the comet assay. Western blot analysis was used to detect the expression of phosphorylated (activated) eNOS, iNOS and NHE1. Results: A dose-dependent decrease in pHi was observed in CP-A cells exposed to bile acids. Bile acid-induced intracellular acidification was abolished when NO production was inhibited by a nonspecific NOS inhibitor L-NAME or by thea specific iNOS inhibitor 1400W. In contrast the NHE inhibitor DMA, significantly decreased the bile acid-mediated pHi response. Exposure of the cells to acidified medium (pH5.5) containing a 0.5mM bile acid cocktail, markedly decreased pHi pHi to a value below extracellular pH. Importantly, medium acidified to pH5.5 containing 0.5mM bile acids induced a similar decrease in pHi as medium acidified to pH 4.5 without bile acids. This The same treatment resulteds in a 250% increase in acid-mediated DNA damage compared to medium acidified to pH5.5 in CP-A cells. Conclusion: In summary, a new mechanism of bile acid induced damage was identified. Bile acids alone or in combination with acidic pH significantly decrease intracellular pH in esophageal cells. The results suggest the effect ofresponse tpo bile acids is the consequence of NOS activation and that leads to NHE inhibition. The mMarked increase in DNA damage after suggests exposure to bile acids in combination with acid may play a crucial role in esophageal carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4105.

The Pathophysiology Gastroesophageal Reflux Disease

ABSTRACT The incidence of Gastroesophageal Reflux Disease (GERD), especially in Indonesia, is increasing with the change of community life-style. Also, the doctors’ perception in understanding clinical manifestation of GERD is alike in addition to the development of diagnostic facilities such as endoscopy in Indonesia. The GERD incidence in Indonesia is as high as the incidence in developed countries. Esophageal reflux develops in physiological condition, which may be found in normal individual. GERD development is caused by anatomical and physiological disorders such as hereditary or acquired factor; and other factors that may be categorized into offensive factors such as gastric acid, pepsin, bile acid, trypsin and disturbance in defensive factors such as hypotensive Lower Esophageal Sphincter (LES), Transient Lower Esophageal Sphincter Relaxations (TLESR), hiatal hernia, disrupted saliva production, esophageal peristaltic disorder; as well as other factors such as genetic, diet, or certain drugs. Imbalance of such factors may cause pathological repeated esophageal reflux which may damage esophageal mucosa and lead to GERD development including all of complications. Keywords : esophageal reflux, GERD, LES

The pattern of bile salt reflux and acid secretion in sliding hiatal hernia

Abstract The role played by gastric fluid refluxed from the stomach into the oesophagus of patients with symutomatic sliding hiatal hernia has been evaluated in terms of gastric bile salt concentration and acid secretion rates. Patients with a peptic stricture had a higher basal acid output than control subjects. Approximately half of both hiatal hernia groups studied had periods of increased total bile salt concentrations either while fasting or following a test meal, This would indicate abnormal pyloric function in these patients. The quantitative examination of total and individual bile salts in solution in gastric juice suggests that a combination of gastric acid pepsin and bile may be a major, factor in the pathogenesis of the clinical responses to gastrooesophageal reflux. Neither total nor individual bile salt concentrations found in gastric juice helped to differentiate between the specific types of response seen in symptomatic sliding hiatal hernia.

Effects and Mechanism of Changes of Local Neurotransmitters in Rats' Pylorus and Bile Reflux to the Stomach with Stress Ulcer

Stress ulcer occurs primarily in severe conditions, with a high incidence and mortality in intensive care units. However, studies on the association between stress ulcer and bile reflux to the stomach with stress ulcer are still inconclusive. Therefore, our research aimed to determine whether or not bile reflux exists during stress ulcer and then to investigate the effects and mechanism of changes of pyloric local neurotransmitters on bile reflux in such circumstances so as to provide a new pathway for clinical intervention. Cold water immersion was used to copy the stress ulcer model of rats. Sixty-five adult Sprague-Dawley rats of either sex were randomly divided into three groups: the normal control group (n = 10), the stress group (n = 30), and the antagonist group (n = 25). The gastric ulcer index, pH, and bile acid of gastric juice were measured before and after stress. Radio Immunoassay Detection Kit and Biochemic Detection Kit were used to measure local contents of CGRP (calcitonin gene-related peptide) and nitric oxide, respectively, in rats' pylorus. The local contents of nitric oxide in rats' pylorus reached a maximum at 1 hr after stress. The bile acid and pH of gastric juice peaked at 2 hr after stress and the ulcer index peaked at 4 hr after stress. But the local contents of CGRP in rats' pylorus decreased to the minimum at 4 hr after stress. The bile acid and ulcer index in the L-NAME group were significantly lower than in the antagonist control group. However, the bile acid in the hCGRP8-37 group was less than in the antagonist control group. Compared with hCGRP8-37 group, there was a significant reduction in bile acid in the L-NAME group. There was a significant reduction in the ulcer index of the hCGRP8-37 group compared with the L-NAME group and the antagonist control group. There was a certain kind of positive correlation between nitric oxide in rats' pylorus and bile acid to the stomach, for nitric oxide could loosen the pyloric sphincter and increase the bile acid to the stomach. L-NAME might reduce the local nitric oxide contents in rats' pylorus so that bile acid to the stomach might be decreased, obviously with a looser tight pyloric sphincter. Meanwhile, the CGRP in rats' pylorus was negatively associated with the ulcer index, hence CGRP might protect gastric mucosa under stress conditions.

Effects of pyloric local CGRP and NO on bile reflux in rat stomach with stress ulcer

AIM: To investigate the effects of pyloric local CGRP and NO on bile reflux in rat stomach with stress ulcer. METHODS: Rats stress ulcer model was established by cold water soaking. Sixty-five rats were divided into three groups: normal control group, the stress group and the antagonist group. The gastric ulcer index, pH and bile acid of gastric juice were measured before and after stress. The pyloric local CGRP was measured by a radioimmu- noassay detection kit. The pyloric local nitric oxide was measured by a biochemic detection kit. RESULTS: The pyloric local nitric oxide reached the climax at 1 hour after stress. The bile acid and pH of gastric juice reached the maximum at 2 hours after stress. The ulcer index did it at 4 hours after stress. But the pyloric local CGRP decreased to the minimum at 4 hours after stress. The bile acid and ulcer index in L-NAME group decreased significantly compared with those of h-CGRP8-37 group. However, the bile acid of hCGRP837 group was less than that of antagonist control group, which was weaker than that in L-NAME group.

Effects of bile reflux and intragastric microflora changes on lesions of remnant gastric mucosa after gastric operation.

To investigate the effects of bile reflux and intragastric microflora changes on lesions of remnant gastric mucosa after gastric operation. Concentration of bile acid and total bacterial counts (TBC) in gastric juice were measured in 49 patients with peptic ulcer before and after gastrectomy. One year after the operation, sample of gastric mucosa taken from all the patients were used for histological examination. The concentration of gastric bile acid was significantly increased in group B-I, or B-II and SV+A than that in group HSV (P<0.05-0.01). The abnormal histological changes in the remnant gastric mucosa were more common in the first 2 groups than in the last group. The type of gastrectomy can affect bile reflux. The abnormal histological changes in the remnant gastric mucosa are closely related to the elevation of bile acid concentration and increase of TBC in gastric juice. HSV can effectively prevent bile reflux and keep the gastric physiological functions stable.

Inhibitory potency of twice-a-day omeprazole on gastric acidity is enhanced by eradication of H. pylori in duodenal ulcer patients.

The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to be greater in the presence than in the absence of an H. pylori infection. It is unknown if this effect persists when a higher dose of omeprazole is taken. We undertook both 24-hr pH-metry and 24-hr aspiration studies in 12 H. pylori-positive patients with a history of duodenal ulcer (DU); (1) when not on omeprazole; (2) when on omeprazole 20 mg twice a day for 8 days; (3) two months after eradication of H. pylori and when not on omeprazole; and (4) after eradication of H. pylori and when on omeprazole twice a day. Eradication of H. pylori in DU results in lower mean and median pH; decreased percent pH > or = 3/ > or = 4, and greater median H+ after breakfast, after lunch, and overnight; and omeprazole appears to have less of a pH-elevating effect in the absence than in the presence of an H. pylori infection. The fall in gastric juice NH3 concentration as a result of eradicating H. pylori partially explained the lower pH-elevating effect of omeprazole. The variation in acid inhibitory effect of omeprazole after as compared with before eradication of H. pylori could not be explained by differences; (1) in gastric juice concentrations of IL-1alpha, IL-8, IL-13, or epidermal growth factor; (2) in the fasting or fed total concentration of gastric juice bile acids; (3) in the fasting concentrations or area under-the-curve (AUC) of the gastric H+ concentrations in response to food; or (4) in the pharmacokinetics of omeprazole. The difference in H+ AUC without omeprazole minus with omeprazole was actually greater when compared after versus before eradication of H. pylori. Thus, in DU the pH-elevating potency of omeprazole taken twice a day is greater in the presence than in the absence of an H. pylori infection.

Bile acid reflux and possible inhibition of Helicobacter pylori infection in subjects without gastric surgery.

Bile acids are generally known to inhibit growth of Helicobacter pylori in vitro, but whether they do so in humans with no gastric surgery has been uncertain. The present study addresses this issue. Among healthy control subjects with preserved acid secretion, H. pylori-positive subjects were older and had lower gastric bile acid concentrations than H. pylori-negative subjects (P < 0.05). Among gastric ulcer patients with preserved acid secretion, H. pylori-positive patients had a higher basal acid output than H. pylori-negative patients (P < 0.05). Among H. pylori-positive subjects with preserved acid secretion, duodenal ulcer patients had a higher basal and maximum acid output than healthy control subjects (P < 0.01). In conclusion, gastric bile acids may suppress initial stages of H. pylori infection in subjects without gastric surgery. However gastric bile acids may have little effect on peptic ulcer disease, once H. pylori infection is established.