The gastrointestinal aspects of halitosis

BACKGROUND:

Halitosis is a common human condition for which the exact pathophysiological mechanism is unclear. It has been attributed mainly to oral pathologies. Halitosis resulting from gastrointestinal disorders is considered to be extremely rare. However, halitosis has often been reported among the symptoms related to Helicobacter pylori infection and gastroesophageal reflux disease.

OBJECTIVE:

To retrospectively review the experience with children and young adults presenting with halitosis to a pediatric gastroenterology clinic.

METHODS:

A retrospective chart review of patients diagnosed with halitosis as a primary or secondary symptom was conducted. All endoscopies were performed by the same endoscopist.

RESULTS:

A total of 94 patients had halitosis, and of the 56 patients (59.6%) who were recently examined by a dental surgeon, pathology (eg, cavities) was found in only one (1.8%). Pathology was found in only six of 27 patients (28.7%) who were assessed by an otolaryngology surgeon. Gastrointestinal pathology was found to be very common, with halitosis present in 54 of the 94 (57.4%) patients. The pathology was noted regardless of dental or otolaryngological findings. Most pathologies, both macroscopically and microscopically, were noted in the stomach (60% non-H pylori related), followed by the duodenum and the esophagus. Fifty-two of 90 patients (57.8%) were offered a treatment based on their endoscopic findings. Of the 74 patients for whom halitosis improvement data were available, some improvement was noted in 24 patients (32.4%) and complete improvement was noted in 41 patients (55.4%).

CONCLUSIONS:

Gastrointestinal pathology was very common in patients with halitosis regardless of dental or otolaryngological findings, and most patients improved with treatment.     

Impairment of ghrelin synthesis in Helicobacter pyloricolonized stomach:New clues for the pathogenesis of H.pylori-related gastric inflammation

Ghrelin,the ligand of growth hormone secretagogue receptor 1a,takes part in several functions of the digestive system,including regulation of appetite,energy homeostasis,gastric acid secretion and motility.Ghrelin has also immunoregulatory properties and is supposed to inhibit some inflammatory pathways that can mediate gastric damage.Interestingly,ghrelin synthesis is reduced in the gastric mucosa of patients with Helicobacter pylori(H.pylori)infection,a worldwide condition inducing a T helper(Th)1/Th17 cell responsedriven gastritis,which may evolve towards gastric atrophy and cancer.In this article,we review the available data on the expression of ghrelin in H.pylori infection and discuss how the defective ghrelin synthesis may contribute to sustain the ongoing inflammatory response in this disease.     

Gastric epithelial anti-microbial peptides—histological correlation and influence of anatomical site and peptic ulcer disease

BACKGROUND AND AIMS: Natural anti-microbial peptides are increasingly recognised for their protective effects in mucosal surfaces. We, therefore, aimed at investigating their expression in the human stomach in a range of peptic conditions. METHODS: We assessed the expression of epithelial secretory leukocyte protease inhibitor, human beta-defensins (HBD1 and HBD2), and alpha-defensin (HD5) in gastric biopsies taken from 52 patients, median age of 55 years. Expression of peptide mRNA was determined using real-time quantitative polymerase chain reaction. The activity of gastritis was graded on a 0-3 scale. RESULTS: The antrum had a median secretory leukocyte protease inhibitor of 0.93 and HBD1 of 0.42, compared with 0.13 (P = 0.001) and 0.08 units (P = 0.002) respectively in the gastric body. The antral histological scores correlated positively with HBD2 expression (r = 0.69; P< 0.001) and negatively with HBD1 (r = -0.47; P = 0.006) particularly in the absence of aspirin. Patients with Helicobacter pylori gastritis, gastric or duodenal ulcers had lower expression of HBD1 and greater expression of HBD2 than in controls. The intake of aspirin by patients infected with H. pylori was associated with marked rise in the expression of HD5 and less expression of secretory leukocyte protease inhibitor. CONCLUSIONS: Gastric epithelial anti-microbial peptides are influenced by anatomical site, grade of gastritis, peptic ulceration, and can be modulated by aspirin.     

Non-invasive tests in gastric diseases

Although the gastric cancer incidence is decreasing, this neoplasia remains one of the major causes of oncological mortality. Because of an insidious development, gastric cancer is often diagnosed in an advanced stage and consequently with a poor prognosis. Accurate non-invasive tests should be extremely useful in order to detect gastric neoplasm in an early phase. In clinical practice, there is no reliable bio-marker for detecting this malignant disease. However, intestinal as well as diffuse types of gastric cancer are preceded by gastric mucosa inflammation. Furthermore, the intestinal type of the neoplasia is, generally, related to chronic atrophic gastritis, especially if associated with intestinal metaplasia. In particular, the risk of the neoplasm is linked to both extension and severity of gastric atrophy. Serological parameters such as serum pepsinogens I (PGI) and II (PGII), gastrin-17 (G-17) cytokines (e.g. IL-8), antiparietal cells, IgG anti-Hp and CagA antibodies and lastly ghrelin supply information about either atrophic or inflammatory conditions characterising gastric mucosa. Low PGI and PGI/PGII ratio levels, especially if combined with high G-17 levels, are recognised bio-markers of corpus atrophic gastritis. Low G-17 levels could be, also, suggestive of antral atrophic gastritis. Furthermore, plasmatic ghrelin levels seem to be also a bio-marker of corpus atrophy. Anti-Hp IgG and CagA antibodies as well as PGII levels are able to detect gastric inflammation. Serological parameters could select subjects at risk for gastric mucosa alterations such as inflammation or atrophy, rather than gastric cancer itself. This review analyses the information derived from serological bio-markers as well as the involved clinical studies.     

Correlation Between Gastrointestinal Symptoms and Gastric Leptin and Ghrelin Expression in Patients with Gastritis

The purpose of this study was to examine the changes in gastric ghrelin and leptin with respect to Helicobacter pylori infection and whether such changes affect the plasma levels of leptin and ghrelin. In addition, we examined the relationship between changes in gastric mucosal ghrelin and leptin levels and gastrointestinal symptoms. Sixty-three patients diagnosed with chronic gastritis were enrolled in the study. Twenty-nine patients were Helicobacter pylori negative and 34 were Helicobacter pylori positive. Expression of ghrelin and leptin mRNA in the gastric mucosa was measured using endoscopic biopsies from the fundus. Plasma levels of ghrelin and leptin were measured by radioimmunoassay. Expression of leptin mRNA in the gastric mucosa was significantly higher in Helicobacter pylori-positive patients than in negative patients (0.38 ± 0.17 vs. 0.24 ± 0.12, p = 0.039). The expression of ghrelin was lower in positive patients than in the negative group, although this difference was not significant (p = 0.07). However, there was no significant difference in plasma leptin and ghrelin levels. Gastric mucosal ghrelin mRNA expression was significantly lower in patients with dyspepsia than in those without (0.15 ± 0.11 vs. 0.23 ± 0.20, p = 0.05). Helicobacter pylori infection and gastrointestinal symptoms could be associated with leptin and ghrelin expression in the gastric mucosa.     

Low prevalence of idiopathic peptic ulcer disease: An Italian endoscopic survey

Background

Peptic ulcer disease (PUD) represents a common condition, although its incidence is decreasing. Previous studies reported a high rate of idiopathic PUD prevalence.

Aim

To investigate prevalence, relative distribution of etiologic factors and prevalence of complication of PUD in an Italian endoscopic series.

Materials and methods

All gastroscopies performed in adult patients during 3 years were considered. Patients with PUD, with antral and corporal histology, were included in the study. Helicobacter pylori infection was assessed by histology. Idiopathic PUD was defined as an ulcer without evidence H. pylori infection or prior exposure to NSAIDs.

Results

300 patients with PUD out of 11,148 gastroscopies were included in our study accounting for a prevalence of 2.7%. H. pylori-associated PUD was diagnosed in 62.3%, NSAID/aspirin-associated PUD in 22%, H. pylori/NSAID/aspirin-associated PUD in 11.6%, and idiopathic PUD in the remaining 4% of cases. Regarding ulcer complications the logistic regression analysis identified the following significant risk factors for GI bleeding: NSAIDs and/or aspirin use, age >65 years and coexistent gastric and duodenal ulcers.

Conclusion

Our data found a low endoscopic prevalence of peptic ulcer. Both H. pylori infection and NSAIDs and/or aspirin use remain the main determinants and idiopathic ulcer prevalence is very low.     

H. pylori-induced higher C-reactive protein in obese African Americans

African Americans are more susceptible to develop insulin resistance, obesity, Type 2 Diabetes, and coronary heart disease (CHD), and systemic inflammation is central to the pathophysiology of these chronic diseases. African Americans are also more likely to contract H. pylori (cagA) infections during their childhood. However, the contribution of H. pylori infection to the degree of overall systemic inflammation in these chronic diseases is not known. Therefore, we studied 46 apparently healthy African Americans, over 40 years of age who were, infected with H. pylori (cagA). These volunteers were assessed at baseline and after treatment with triple regimen drug therapy to eradicate H. pylori. All but 3 subjects were found to be free of this infection by urea breath test (UBT) after the treatment period. No hyperhomocysteinemia was found in these subjects and there were no significant changes in the level of homocysteine (tHcy), folate and B(12); however, CRP levels measured by high sensitivity assay showed a significant (p=0.02) decrease 2 months after the eradication. We further stratified CRP values according to the BMI < 27 and > 27. There was more profound reduction in CRP in the more obese group (i.e., BMI>27) from 54.26 ± 23.67 to 18.73 ± 17.39 mg/l (p=0.01), compared with the leaner subjects in whom CRP decreases from 8.88 ± 6.23 to 4.94 ± 6.21 mg/L (p=0.04), after eradication of the H. pylori (cagA) infection. The level of CRP, however, remained significantly higher in the obese subjects even after the eradication of this infection, indicative of a smaller residual influence of adiposity on CRP. Thus, a major component of systemic inflammation in African Americans may be attributable to chronic H. pylori infection.     

Current trends in the treatment of upper gastrointestinal disease

The past 25 years have seen an amazing improvement in the treatment and understanding of acid-related disorders. In particular, the introduction of selective histamine receptor antagonists and proton pump inhibitors has made the medical control of acid secretion an effective means of therapy. The demonstration that infection with Helicobacter pylori is responsible for most cases of peptic ulcer disease resulted in another major improvement in therapy in these areas as a result of the eradication of the organism. Research continues in an attempt to find improved means of acid control and better methods for the eradication of H. pylori based on unique proteins expressed by the organism to resist gastric acidity.     

Helicobacter pylori and autoimmune disease:Cause or bystander

Helicobacter pylori(H.pylori)is the main cause of chronic gastritis and a major risk factor for gastric cancer.This pathogen has also been considered a potential trigger of gastric autoimmunity,and in particular of autoimmune gastritis.However,a considerable number of reports have attempted to link H.pylori infection with the development of extra-gastrointestinal autoimmune disorders,affecting organs not immediately relevant to the stomach.This review discusses the current evidence in support or against the role of H.pylori as a potential trigger of autoimmune rheumatic and skin diseases,as well as organ specific autoimmune diseases.We discuss epidemiological,serological,immunological and experimental evidence associating this pathogen with autoimmune diseases.Although over one hundred autoimmune diseases have been investigated in relation to H.pylori,we discuss a select number of papers with a larger literature base,and include Sj grens syndrome,rheumatoid arthritis,systemic lupus erythematosus,vasculitides,autoimmune skin conditions,idiopathic thrombocytopenic purpura,autoimmune thyroid disease,multiple sclerosis,neuromyelitis optica and autoimmune liver diseases.Specific mention is given to those studies reporting an association of anti-H.pylori antibodies with the presence of autoimmune disease-specific clinical parameters,as well as those failing to find such associations.We also provide helpful hints for future research.     

Critical role of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> in the pattern of gastritis and carditis in residents of an area with high prevalence of gastric cardia cancer

We have investigated the role of Helicobacter pylori infection and of other risk factors of gastritis and carditis in residents of a high-risk area for gastric cardia cancer. During a national population-based endoscopic survey, 508 randomly-selected participants aged ≥40 were enrolled. Mucosal biopsies were obtained from six standard sites. Polymorphonuclear (PMN) and mononuclear (MN) infiltration and combined inflammatory scores (CIS) for chronic gastritis and H.pylori were assessed. Relationships of H.pylori and reflux esophagitis with these variables were calculated for cardia and non-cardia subsites. Both PMN and MN infiltrations correlated strongly with H.pylori infection. For PMN the relationship was maximum for the antrum (odds ratio (OR) = 9.4 (5.2–17.1)) and minimum for the gastric body (OR = 1.7 (1.0–2.9)). There was a significant relationship between carditis and H.pylori (OR = 2.8 (1.7–4.9)). A similar relationship was obtained for MN infiltration. In 56% of subjects the mean MN score for the corpus was equal to or greater than that for the antrum. For 59% of subjects the MN score for the cardia was greater than or equal to the antral score. Use of logistic regression revealed that was the main risk factor for gastritis and carditis in all sites. There was an inverse relationship between reflux esophagitis and carditis. H.pylori is the main risk factor for gastritis for all sites of the stomach including the cardia; but this relationship is stronger for the antrum and cardia than for the body. Continuous cardia inflammation may contribute to the high incidence of gastric cardia cancer in this region.     

vacA genotypes of Helicobacter pylori in the oral cavity and stomach of patients with chronic gastritis and gastric ulcer

Introduction

Helicobacter pylori adheres to various components of the human saliva. Therefore, the objective of this research was to simultaneously detect H. pylori in saliva and in gastric biopsy, and to determine the agreement between the vacA genotypes in both saliva and gastric biopsy.

Materials and methods

A total of 162 patients with chronic gastritis and 34 with gastric ulcer were studied, and saliva and biopsy samples were collected from each patient. H. pylori DNA was detected by conventional PCR and nested PCR was used for vacA genotyping.

Results

In 24% of the patients (47/196) H. pylori DNA was found in saliva and in biopsy; 52.5% (103/196) were saliva^negative/biopsy^positive and 6.6% (13/196) were saliva^positive/biopsy^negative. In either or both H. pylori vacAs1m1 or s1m2 genotypes were detected in saliva in 41.5% of the patients with chronic gastritis. Forty-seven percent had >1 genotype, and the s1m1/s1m2 combination was found in 36% of them. H. pylori vacAs1m1 and s1m2 were also found in the saliva and biopsy of patients with gastric ulcer. The genotypes found in saliva and biopsy of the same patient had 51.1% agreement. In 27.6% of the 47 patients saliva^positive/biopsy^positive two genotypes were found in saliva, and one or both in the stomach.

Conclusions

The s1m1/s1m2 genotypes, alone or together, are found simultaneously in saliva and gastric biopsy of the same patient. These results suggest that H. pylori reaches the oral cavity by various ways, and that saliva can be the transmitting and re-infecting vector.     

Campylobacter pylori-related gastrointestinal disease in children

Over a one-year period, 95 children and adolescents presenting with epigastric pain and/or vomiting, and without associated risk factors for development of peptic disease, underwent endoscopic antral biopsies for pathologic diagnosis and to detect presence of Campylobacterss. pylori (C. pylori). Additional biopsies of the esophagus, stomach, and duodenum were obtained for histologic evaluation. C. pylori was identified in 16 patients (16.8%), all of whom had evidence of acute and/or chronic gastritis. Significant discriminating factors between C. pylori-positive and -negative subjects included age at presentation (positive vs negative=14.6 vs 9.9 years, P<0.01, biopsy-confirmed gastritis (100% vs 30.4%, P<0.001), and diagnosis of duodenitis alone (0% vs 46.8%, P<0.001). Risk for bacterial colonization was significantly higher in the presence of endoscopic gastritis (P<0.001). Among C. pylori-positive patients, none responded to standard antiulcer therapy (H₂-receptor antagonists, antacids). Symptomatic and histologic remission was achieved utilizing combined therapy with bismuth subsalicylate and antibiotics. Seven of 79 C. pylori-negative patients with biopsyproven gastritis who responded poorly to antisecretory therapy had the organism identified in follow-up antral biopsies; these patients improved clinically following treatment for C. pylori. These data suggest that C. pylori is a significant factor in the etiology of upper gastrointestinal tract inflammatory disease in pediatrics, and presence of the organism should be evaluated, particularly in children with evidence of acute and/or chronic gastritis.     

Short-term zinc supplementation attenuates Helicobacter felis-induced gastritis in the mouse

BACKGROUND: Mucosal damage by H. pylori infection is mainly caused by neutrophils producing large quantities of reactive oxygen species (ROS). Metallothionein (MT) an intracellular, low-molecular, cysteine-rich protein, which is inducible by dietary zinc (Zn), has been implicated in sequestering ROS. This study examines the effects of Zn supplementation on Helicobacter colonisation and associated gastritis and the relationship with gastric MT levels. METHODS: C57Bl/6 mice were inoculated with either 10(8) H. pylori or H. felis and were infected for 4 weeks or 6 and 12 weeks, respectively. Mice infected with H. pylori (4 weeks) or H. felis (6 weeks) were treated with either Zn acetate (ZnA; 1 mg/ml), or Zn sulphate (ZnSO4; 5 mg/ml) for 2 weeks with 0.1 ml oro-gastric gavage twice daily. H. pylori load and H. felis colonisation density were determined by culture and microscopy, respectively. MT levels and H. felis-induced gastritis were also determined. RESULTS: Zn treatment showed no significant difference in Helicobacter load and gastric MT, however, ZnSO4 treatment showed a significant (p<0.05) increased in gastric MT in H. felis infected mice. Both Zn-treated groups showed a significant (p<0.05) difference in gastritis score in the antrum of the stomach within the basal and submucosal compartments compared to H. felis-infected controls. CONCLUSIONS: We found that H. felis-induced gastritis can be attenuated by short-term treatment of Zn. This observation suggests that Zn alone may be effective for the suppression of gastric mucosal inflammation induced by Helicobacter.     

Circulating Ghrelin Levels in Patients with Various Upper Gastrointestinal Diseases

The stomach is the main source of circulating ghrelin. Plasma concentrations of this hormone in patients with various upper gastrointestinal diseases remain undetermined. Thus we measured plasma ghrelin levels by radioimmunoassay in 225 subjects, including 134 Helicobacter pylori-infected and 91 uninfected subjects. They included 67 patients with chronic gastritis (CG), 26 with benign gastric polyp (BGP), 24 with gastric ulcer (GU), 24 with reflux esophagitis (RE), 18 with duodenal ulcer (DU), 28 with acute gastritis (AG), 23 with gastric cancer (GC), and 39 who had normal mucosa on upper endoscopy (N). Plasma pepsinogen I and II levels were also measured. The extent of gastritis was assessed endoscopically. Ghrelin levels differed significantly among the different disease groups. Plasma ghrelin concentrations were lowest in the CG group, followed by the GU group, and highest in the AG patients. There was a significant difference in the levels between differentiated and undifferentiated GC. Ghrelin concentrations in BGP, RE, and DU patients were comparable to those in the N group. Ghrelin circulating levels were lower in H. pylori-positive than –negative individuals, but the significant differences among disease groups were still observed in H. pylori-infected and uninfected populations. Ghrelin concentrations correlated positively with plasma pepsinogen I levels and I/II ratios and inversely with the extent of H. pylori-related gastritis. Plasma ghrelin levels varied widely in diverse conditions of the upper digestive tract, reflecting the inflammatory and atrophic events of the background gastric mucosa. Further investigation is warranted to unravel the mechanisms of the high circulating ghrelin levels in certain upper gastrointestinal diseases.     

Different risk factors influence peptic ulcer disease development in a Brazilian population

AIM: To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients.tients submitted to upper gastroscopy at Hospital das Clinicas of Marilia, antral biopsy specimens were obtained and subjected to histopathology and H. pylori diagnosis. All patients presenting chronic gastritis (CG) and peptic ulcer (PU) disease localized in the stomach, gastric ulcer (GU) and/or duodenal ulcer (DU) were included in the study. Gastric biopsies (n = 668) positive for H. pylori by rapid urease test were investigated for vacuolating cytotoxin A (vacA ) medium (m) region mosaicism by polymerase chain reaction. Logistic regression analysis was performed to verify the association of age, sex, histopathologic alterations, H. pylori diagnosis and vacA m region mosaicism with the incidence of DU, GU and CG in patients. RESULTS: Of 1466 patients submitted to endoscopy, 1060 (72.3%) presented CG [male/female = 506/554; mean age (year) ± SD = 51.2 ± 17.81], 88 (6.0%) presented DU [male/female = 54/34; mean age (year) ± SD = 51.4 ± 17.14], and 75 (5.1%) presented GU [male/female = 54/21; mean age (year) ± SD = 51.3 ± 17.12] and were included in the comparative analysis. Sex and age showed no detectable effect on CG incidence (overall c 2 = 2.1, P = 0.3423). Sex [Odds ratios (OR) = 1.8631, P = 0.0058] but not age (OR = 0.9929, P = 0.2699) was associated with DU and both parameters had a highly significant effect on GU (overall c 2 = 30.5, P 0.0001). The histopathological results showed a significant contribution of ageing for both atrophy (OR = 1.0297, P 0.0001) and intestinal metaplasia (OR = 1.0520, P 0.0001). Presence of H. pylori was significantly associated with decreasing age (OR = 0.9827, P 0.0001) and with the incidence of DU (OR = 3.6077, P 0.0001). The prevalence of m1 in DU was statistically significant (OR = 2.3563, P = 0.0018) but not in CG (OR = 2.678, P = 0.0863) and GU (OR = 1.520, P = 0.2863). CONCLUSION: In our population, male gender was a risk factor for PU; ageing for GU, atrophy and metapla-sia; and H. pylori of vacA m1 genotype for DU.     

Pantoprazole in severe acid-peptic disease: the effectiveness and safety of 5 years’ continuous treatment

OBJECTIVE: This is our final report on the clinical effectiveness and safety of long-term pantoprazole in patients with severe peptic ulcer or reflux disease during continuous treatment for up to 5 years. METHODS: Patients (n= 150) with peptic ulcer or reflux erosive oesophagitis running an aggressive course or with complications, and refractory to H2-receptor antagonists, were entered into this 5-year programme. Assessment was by serial endoscopy, clinical examination, serum gastrin estimation, gastric mucosal histology and mucosal endocrine cell quantification. RESULTS: Healing results were presented earlier. The estimated rates of remission on maintenance treatment with pantoprazole (n = 115) were 82% at 1 year, 75% at 2 years, 72% at 3 years, 70% at 4 years and 68% at 5 years. Helicobacter pylori infection appeared not to influence the outcome in reflux patients, with roughly two-thirds continuing in remission irrespective of infection. Only four patients had adverse events considered to be definitely related to pantoprazole. Median gastrin levels rose by 1.5-2-fold and were higher in those with H. pylori infection; 13 patients had levels >500 ng/L on at least one occasion, but these high levels were not sustained. Histological changes were more marked in patients infected with H. pylori: chronic gastritis decreased in the antrum and increased in the corpus, which also showed atrophic changes. The total number of endocrine cells in the antrum showed little variation over 60 months but fell by around one-third in the corpus. CONCLUSION: Long-term treatment with pantoprazole is effective and safe.     

Helicobacter pylori Infection with Atrophic Gastritis Is an Independent Risk Factor for Advanced Colonic Neoplasm

Background/AimsHelicobacter pylori is a major risk factor for atrophic gastritis (AG) and gastric cancer. The correlation between H. pylori, AG and colorectal neoplasm (CRN) has only been examined in a limited number of studies, and findings have been inconclusive. We aimed to investigate the association between H. pylori infection status, AG and advanced CRN.MethodsThis cross-sectional study investigated the relationship between the presence of serum anti-H. pylori IgG antibodies, AG, and advanced CRN in 6,351 consecutive asymptomatic subjects who underwent a screening colonoscopy.ResultsA total of 316 participants (5.0%) had advanced CRN. H. pylori seropositivity was 61.3%. In a univariate analysis, the presence of H. pylori infection was associated with advanced CRN (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17 to 1.91; p=0.001). H. pylori infection was associated with an increased risk of advanced CRN after adjusting for clinically relevant confounders (OR, 1.34; 95% CI, 1.04 to 1.72; p=0.023). H. pylori-related AG was significantly associated with the risk of advanced CRN (OR, 1.40; 95% CI, 1.03 to 1.91; p=0.030), whereas H. pylori infection without AG was not.ConclusionsH. pylori infection increased the risk of advanced CRN, especially when it was combined with AG. Strict colonoscopy screening and surveillance may be warranted in those with H. pylori-positive AG.