Helicobacter pylori and Upper Endoscopy in Systemic Sclerosis: A Cross-sectional Study in the Real World.

BACKGROUND/AIMS: A role for Helicobacter pylori in triggering systemic sclerosis (SSc) has been proposed, but data are conflicting. In previous studies, infection has been generally searched for by using serology. We designed this study to assess H. pylori prevalence in SSc patients with histology of gastric mucosa, considered the criterion standard for infection diagnosis. METHODS: This cross-sectional study enrolled 30 SSc patients who complained of upper gastrointestinal symptoms. All underwent upper endoscopy with gastric biopsies. Endoscopic alterations were recorded, and gastric mucosa biopsies were used for both histological examination and searching for H. pylori. The role for proton-pump inhibitor (PPI) therapy was considered. Fisher exact test was used for statistical analysis. RESULTS: Data of 28 SSc patients were available, 14 with ongoing PPI therapy. Helicobacter pylori infection at histology was detected in 14.3% patients, and it equally occurred in patients with or without PPI therapy. Erosive esophagitis/Barrett esophagus was detected in 26.6% of cases. Among patients with PPI therapy, 30% received half dose only. The prevalence of intestinal metaplasia was low (14.3%). Endoscopic esophageal alterations were significantly more frequent in those patients showing anti-Scl70 antibody positivity. CONCLUSIONS: This study showed that prevalence of H. pylori is very low in SSc patients, so that it seems not having a role in triggering SSc. Management of gastroesophageal diseases in SSc patients needs to be improved, and looking to the autoimmune profile may be of help. Thus, collaboration between rheumatologist and gastroenterologist is highly recommended.

A microbiota-centric view of diseases of the upper gastrointestinal tract.

The distinctive anatomy and physiology of the upper gastrointestinal tract and the difficulty of obtaining samples led to the theory that it was bacteria free. However, multiomics studies are indicating otherwise. Although influenced by both oral and gastric bacteria, the resident microbial ecosystem in the oesophagus is dominated by Streptococcus. A shift from Gram-positive to Gram-negative bacteria occurs in oesophagitis and Barrett's oesophagus, and this shift might be involved in the pathogenesis of oesophageal adenocarcinoma. The gastric microenvironment is populated by microbial communities mainly of the Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria phyla and species of the Lactobacillus, Streptococcus, and Propionibacterium genera. The composition of gastric microbiota is highly dynamic, and is influenced by acid suppression, gastric inflammation, and Helicobacter pylori. Duodenal microbes are also implicated in the onset and outcome of coeliac disease. Bacteria of the genera Bacteroides, Clostridium, and Staphylococcus dominate the duodenal flora in active coeliac disease whereas lactobacilli and bifidobacteria decrease. Although knowledge of the composition of the microbiota of the upper gastrointestinal tract has advanced substantially, this information is far from being translated to the clinical setting. In this Review, we assess the data related to the potential contribution of microbes to the susceptibility for and pathogenesis of upper gastrointestinal diseases.

Bacterial Composition of the Human Upper Gastrointestinal Tract Microbiome Is Dynamic and Associated with Genomic Instability in a Barrett's Esophagus Cohort.

BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) has increased nearly five-fold over the last four decades in the United States. Barrett's esophagus, the replacement of the normal squamous epithelial lining with a mucus-secreting columnar epithelium, is the only known precursor to EAC. Like other parts of the gastrointestinal (GI) tract, the esophagus hosts a variety of bacteria and comparisons among published studies suggest bacterial communities in the stomach and esophagus differ. Chronic infection with Helicobacter pylori in the stomach has been inversely associated with development of EAC, but the mechanisms underlying this association remain unclear. METHODOLOGY: The bacterial composition in the upper GI tract was characterized in a subset of participants (n=12) of the Seattle Barrett's Esophagus Research cohort using broad-range 16S PCR and pyrosequencing of biopsy and brush samples collected from squamous esophagus, Barrett's esophagus, stomach corpus and stomach antrum. Three of the individuals were sampled at two separate time points. Prevalence of H. pylori infection and subsequent development of aneuploidy (n=339) and EAC (n=433) was examined in a larger subset of this cohort. RESULTS/SIGNIFICANCE: Within individuals, bacterial communities of the stomach and esophagus showed overlapping community membership. Despite closer proximity, the stomach antrum and corpus communities were less similar than the antrum and esophageal samples. Re-sampling of study participants revealed similar upper GI community membership in two of three cases. In this Barrett's esophagus cohort, Streptococcus and Prevotella species dominate the upper GI and the ratio of these two species is associated with waist-to-hip ratio and hiatal hernia length, two known EAC risk factors in Barrett's esophagus. H. pylori-positive individuals had a significantly decreased incidence of aneuploidy and a non-significant trend toward lower incidence of EAC.

Association between tobacco use and the upper gastrointestinal microbiome among Chinese men.

PURPOSE: Tobacco causes many adverse health conditions and may alter the upper gastrointestinal (UGI) microbiome. However, the few studies that studied the association between tobacco use and the microbiome were small and underpowered. Therefore, we investigated the association between tobacco use and the UGI microbiome in Chinese men. METHODS: We included 278 men who underwent esophageal cancer screening in Henan Province, China. Men were categorized as current, former, or never smokers from questionnaire data. UGI tract bacterial cells were characterized using the Human Oral Microbial Identification Microarray. Counts of unique bacterial species and genera estimated alpha diversity. For beta diversity, principal coordinate (PCoA) vectors were generated from an unweighted UniFrac distance matrix. Polytomous logistic regression models were used for most analyses. RESULTS: Of the 278 men in this study, 46.8% were current smokers and 12.6% were former smokers. Current smokers tended to have increased alpha diversity (mean 42.3 species) compared to never smokers (mean 38.9 species). For a 10 species increase, the odds ratio (OR) for current smoking was 1.29 (95% CI 1.04-1.62). Beta diversity was also associated with current smoking. The first two PCoA vectors were strongly associated with current smoking (PCoA1 OR 0.66; 95% CI 0.51-0.87; PCoA2 OR 0.73; 95% CI 0.56-0.95). Furthermore, Dialister invisus and Megasphaera micronuciformis were more commonly detected in current smokers than in never smokers. CONCLUSIONS: Current smoking was associated with both alpha and beta diversity in the UGI tract. Future work should consider how the UGI microbiome is associated with smoking-related diseases.

Endoscopic and pathologic changes of the upper gastrointestinal tract in Crohn's disease.

BACKGROUND: Crohn's disease (CD) may involve any part of the gastrointestinal tract. We assessed the prevalence and features of upper gastrointestinal (UGI) lesions in CD. METHODS: This was a retrospective study that included 138 CD patients that underwent esophagogastroduodenoscopy (EGD). The rate of Crohn's specific endoscopic lesions in the esophagus, stomach, and duodenum was assessed, and immunohistochemical analysis was performed. Changes in the UGI lesions were assessed in those who had two or more EGD. RESULTS: Of 138 patients, 51.3% had Crohn's specific UGI lesions. The rates of Crohn's specific lesion in the esophagus, upper-to-middle stomach, lower stomach, duodenal bulb, and 2nd portion of the duodenum were 6.5%, 47.8%, 24.6%, 31.9%, and 18.1%, respectively. Granulomas were detected in 6.1%, 25.0%, and 11.4% in the upper-to-middle stomach, lower stomach, and duodenal bulb, respectively, but none in the esophagus and 2nd portion of the duodenum. Thirty-seven were analyzed for Helicobacter pylori and 4 were positive (10.8%). Improvements of UGI lesions were seen in 14 out of 49 (28.5%) and were unchanged in 59.2% and worsened in 12.2%. CONCLUSIONS: The prevalence of Crohn's specific UGI lesions was common in our case series, and immunohistochemical studies suggested that the majority was unrelated to Helicobacter pylori infection. Worsening of UGI lesions over the course was rare.

Low prevalence of H. pylori infection in HIV-positive patients in the northeast of Brazil.

BACKGROUND: This study conducted in Northeastern Brazil, evaluated the prevalence of H. pylori infection and the presence of gastritis in HIV-infected patients. METHODS: There were included 113 HIV-positive and 141 age-matched HIV-negative patients, who underwent upper gastrointestinal endoscopy for dyspeptic symptoms. H. pylori status was evaluated by urease test and histology. RESULTS: The prevalence of H. pylori infection was significantly lower (p < 0.001) in HIV-infected (37.2%) than in uninfected (75.2%) patients. There were no significant differences between H. pylori status and gender, age, HIV viral load, antiretroviral therapy and the use of antibiotics. A lower prevalence of H. pylori was observed among patients with T CD4 cell count below 200/mm3; however, it was not significant. Chronic active antral gastritis was observed in 87.6% of the HIV-infected patients and in 780.4% of the control group (p = 0.11). H. pylori infection was significantly associated with chronic active gastritis in the antrum in both groups, but it was not associated with corpus chronic active gastritis in the HIV-infected patients. CONCLUSION: We demonstrated that the prevalence of H. pylori was significantly lower in HIV-positive patients compared with HIV-negative ones. However, corpus gastritis was frequently observed in the HIV-positive patients, pointing to different mechanisms than H. pylori infection in the genesis of the lesion.

Microbiological and immunological effects of enteral feeding on the upper gastrointestinal tract.

Enteral feeding via a percutaneous endoscopic gastrostomy tube is required for nutritional support in patients with dysphagia. Enteral tube feeding bypasses the innate defence mechanisms in the upper gastrointestinal tract. This study examined the surface-associated microbial populations and immune response in the gastric and duodenal mucosae of eight enteral nutrition (EN) patients and ten controls. Real-time PCR and fluorescence in situ hybridization were employed to assess microbiota composition and mucosal pro-inflammatory cytokine expression. The results showed that EN patients had significantly higher levels of bacterial DNA in mucosal biopsies from the stomach and duodenum (P<0.05) than the controls, and that enterobacteria were the predominant colonizing species on mucosal surfaces in these individuals. Expression of the pro-inflammatory cytokines interleukin (IL)-1α, IL-6 and tumour necrosis factor-α was significantly higher in gastric and small intestinal mucosae from patients fed normal diets in comparison with those receiving EN (P<0.05). These results indicate that EN can lead to significant bacterial overgrowth on upper gastrointestinal tract mucosae and a significantly diminished pro-inflammatory cytokine response.

Design of 16S rRNA gene primers for 454 pyrosequencing of the human foregut microbiome.

AIM: To design and validate broad-range 16S rRNA primers for use in high throughput sequencing to classify bacteria isolated from the human foregut microbiome. METHODS: A foregut microbiome dataset was constructed using 16S rRNA gene sequences obtained from oral, esophageal, and gastric microbiomes produced by Sanger sequencing in previous studies represented by 219 bacterial species. Candidate primers evaluated were from the European rRNA database. To assess the effect of sequence length on accuracy of classification, 16S rRNA genes of various lengths were created by trimming the full length sequences. Sequences spanning various hypervariable regions were selected to simulate the amplicons that would be obtained using possible primer pairs. The sequences were compared with full length 16S rRNA genes for accuracy in taxonomic classification using online software at the Ribosomal Database Project (RDP). The universality of the primer set was evaluated using the RDP 16S rRNA database which is comprised of 433 306 16S rRNA genes, represented by 36 phyla. RESULTS: Truncation to 100 nucleotides (nt) downstream from the position corresponding to base 28 in the Escherichia coli 16S rRNA gene caused misclassification of 87 (39.7%) of the 219 sequences, compared with misclassification of only 29 (13.2%) sequences with truncation to 350 nt. Among 350-nt sequence reads within various regions of the 16S rRNA gene, the reverse read of an amplicon generated using the 343F/798R primers had the least (8.2%) effect on classification. In comparison, truncation to 900 nt mimicking single pass Sanger reads misclassified 5.0% of the 219 sequences. The 343F/798R amplicon accurately assigned 91.8% of the 219 sequences at the species level. Weighted by abundance of the species in the esophageal dataset, the 343F/798R amplicon yielded similar classification accuracy without a significant loss in species coverage (92%). Modification of the 343F/798R primers to 347F/803R increased their universality among foregut species. Assuming that a typical polymerase chain reaction can tolerate 2 mismatches between a primer and a template, the modified 347F and 803R primers should be able to anneal 98% and 99.6% of all 16S rRNA genes in the RDP database. CONCLUSION: 347F/803R is the most suitable pair of primers for classification of foregut 16S rRNA genes but also possess universality suitable for analyses of other complex microbiomes.

Microbial colonization of the upper gastrointestinal tract in patients with Barrett's esophagus.

BACKGROUND: Barrett's esophagus (BE) is a complication of chronic gastroesophageal reflux disease, in which patients are at greatly increased risk of esophageal dysplasia and adenocarcinoma. Over the past 2 decades, there has been an increase in the incidence of both BE and adenocarcinoma; however, the involvement of microorganisms in BE is uncertain. The aim of this study was to characterize microbial communities in esophageal aspirate specimens and on distal esophageal mucosal samples from patients with BE. METHODS: Biopsy and aspirate specimens were obtained by endoscopic examination from 7 patients with BE and 7 control subjects without BE. Samples were cultured under aerobic, anaerobic, and microaerophilic conditions for yeasts and bacteria, including Helicobacter pylori. Bacterial isolates were identified by 16S ribosomal RNA gene sequencing. Fluorescence microscopic examination was also used to determine the spatial localization of these organisms on mucosal surfaces. Significant colonization was detected in 6 patients with BE and in 4 control subjects. RESULTS: Overall, 46 bacterial species belonging to 16 genera were detected, with 10 species being common in both groups. Both aspirate and biopsy samples from patients with BE contained complex populations of bacteria. Uniquely, high levels of Campylobacter species (Campylobacter concisus and Campylobacter rectus), which have been linked to enteritis, periodontal infections, and tumor formation in animals, were found in 4 (57%) of 7 patients with BE but in none of the control subjects. Microscopic examination revealed that bacteria on mucosal biofilms often occurred in microcolonies. CONCLUSIONS: The occurrence of nitrate-reducing Campylobacter species in patients with BE may suggest that there is a link in either the initiation, maintenance, or exacerbation of disease processes leading to adenocarcinoma formation.

Review article: proton pump inhibitors and bacterial overgrowth.

Proton pump inhibitors are potent drugs producing profound suppression of gastric acid secretion. Consequently, they are highly effective at treating acid-related disorders. There have been concerns that the suppression of gastric acid will alter the bacterial flora of the upper gastrointestinal tract and lead to complications such as cancer, enteric or other infections and malabsorption. Studies have confirmed that proton pump inhibitors do alter the bacterial population but present evidence indicates that this only rarely leads to clinical disease. As with all drugs, proton pump inhibitors should only be used for disorders shown clearly to benefit from the therapy and where the benefits will outweigh the small risks associated with them. Further research to more fully quantify the risk associated with PPI therapy is required.

Gastrointestinal luminal tuberculosis: establishing the diagnosis.

BACKGROUND AND AIM: To study the profile of gastrointestinal luminal tuberculosis (GITB) patients who have been treated on a confirmed and a presumptive diagnosis. METHODS: A total of 260 patients who had an initial diagnosis of GITB were included in this retrospective analysis. Clinical, radiologic, endoscopic, histopathologic and microbiologic features of these patients were studied in detail. RESULTS: GITB was confirmed in 66.5% patients (cGITB), while 29.5% had presumed GITB (pGITB). In 3.9% patients, Crohn's disease (CD) was misdiagnosed initially as GITB. There was no significant difference in the clinical and radiologic features except a higher incidence of a radiologically abnormal ileocecal region in cGITB patients. Endoscopic biopsies from ulcerated masses and ulcers had the highest yield of confirmation (100% and 68%, respectively) when subjected to histopathology, acid-fast bacilli smear and culture studies. Confirmed diagnosis was obtained in 100% of cases occurring in the upper gastrointestinal tract, 66% of cases in the ileocecal region/colon and 40% of cases that had small bowel involvement. In 21% of cases, extraluminal sites helped to confirm the diagnosis. As the presence of diarrhea, bleeding, fistulae, perianal disease and extraintestinal manifestations favored a diagnosis of CD, the presence of these features initially or on subsequent follow up helped to minimize the misdiagnosis of GITB. CONCLUSIONS: As a differential diagnosis, CD must be ruled out before starting treatment for GITB. In our study, an intense search for histologic and microbiologic proof of the presence of TB from luminal and extraluminal sites established the diagnosis in 66.5% of cases. Surgery for establishing the diagnosis should be reserved for complicated cases.

[Is it necessary to treat Helicobacter pylori infection in patients with end-stage renal failure and in renal transplant recipients?]. / Czy nalezy leczyc zakazenie Helicobacter pylori u chorych w okresie skrajnej niewydolnosci nerek i po przeszczepieniu nerek?

Uraemic patients frequently complain of gastrointestinal ailments. There are a lot of factors responsible for the occurrence of these symptoms. It is considered--among other things--that high level of urea in gastric juice and hypergastrinaemia contribute to the damage of stomach and duodenum mucosa. Does H. pylori infection also produce pathological changes within upper gastrointestinal tract in these patients? The aim of the study was to determine the prevalence of H. pylori infection and macroscopic and microscopic estimation of oesophagus, stomach and duodenum mucosa in haemodialysis patients and renal transplant recipients. A total of 39 patients were taken under investigation: 27 among them were treated with haemodialyses and 12 were after kidney transplantation. In all patients upper gastrointestinal endoscopies were performed with collection of biopsy specimens for histological analysis and a urease test. Serological examinations were carried out in order to detect anti-CagA H. pylori antibody. In summary, we found that prevalence of H. pylori infection in uremic patients on chronic haemodialysis and renal transplant recipients was significantly lower than that in patients with normal renal function. This may be a consequence of medication and/or protection by a high urea concentration. Elevated blood urea seems to correlate with a high prevalence of gastroduodenal mucosal lesions.