Prolonged Intake of Luvos Healing Earth does not alter the Composition of the Gut Microbiota in Patients with Diarrhea-predominant Irritable Bowel Syndrome and Healthy Controls.

BACKGROUND AND AIMS: The mineral compound Luvos Healing Earth (LHE) is a commercially available remedy empirically used for a variety of gastrointestinal disorders. The aim of this study was to investigate the possible effect of prolonged LHE therapy on gut microbiota in healthy individuals and in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: In this prospective exploratory study, a total of 20 participants, including 12 healthy controls and 8 patients with IBS-D, received treatment with LHE (Magenfein Granulat, 1 sachet bid) for 6 weeks. Fecal samples were collected for microbiota analysis in the morning fasting state at regular intervals at 6 different timepoints: 2 weeks before starting therapy (Screen), and every 2 weeks during LHE therapy (V0-V3). Additionally, a follow-up visit was scheduled 4 weeks after the end of treatment (V4). Microbiota analysis was performed using the GA-map® Dysbiosis Test Lx v2. Dysbiosis Index, bacterial diversity, as well as the balance or imbalance of functionally important bacteria were assessed. RESULTS: The microbiota analysis revealed an overlap in gut microbiota profiles between healthy controls and patients with IBS-D. Bacterial communities were consistently stable during the entire treatment period, and no significant variations in composition were observed 4 weeks after the end of the therapeutic intervention. There was a remarkable stability of microbiota profiles over time within each individual and a high inter-individual variation. The majority of fecal samples exhibited profiles, reflecting an eubiotic state, with no significant changes in dysbiosis index, functional bacteria profiles, or bacterial diversity. CONCLUSION: Our findings indicate intraindividual resilience of microbiota consortia during the entire study period. Prolonged intake of LHE does not cause significant alterations in fecal microbiota profiles in healthy controls and patients with IBS-D. Luvos Healing Earth does not affect the stability of gut microbial diversity and bacterial functions.

A multiserological line assay to potentially discriminate current from past Helicobacter pylori infection.

OBJECTIVES: Early diagnosis is important in controlling Helicobacter pylori-induced gastritis and progression to gastric malignancy. Serological testing is an efficient non-invasive diagnostic method, but currently does not allow differentiation between active and past infections. To fill this diagnostic gap we investigated the diagnostic value of a panel of ten H. pylori-specific antibodies in individuals with different H. pylori infection status within a German population. METHODS: We used the recomLine Helicobacter IgG 2.0 immunoblotting assay to analyse ten H. pylori-specific antibodies in serum samples collected from 1108 volunteers. From these, 788 samples were used to build exposure and infection status models and 320 samples for model validation. H. pylori infection status was verified by histological examination. We applied logistic regression to select antibodies correlated to infection status and developed, with independent validation, discriminating models and risk scores. Receiving operating characteristic analysis was performed to assess the accuracy of the discriminating models. RESULTS: Antibody reactivity against cytotoxin-associated gene A (CagA), H. pylori chaperone (GroEL), and hook-associated protein 2 homologue (FliD) was independently associated with the risk of H. pylori exposure with ORs and 95% CIs of 99.24 (46.50-211.80), 46.17 (17.45-122.17), and 22.16 (8.46-55.04), respectively. A risk score comprising these three selected antibodies differentiated currently H. pylori infected or eradicated participants from negatives with an area under the curve of 0.976 (95% CI: 0.965-0.987) (Model 1). Seropositivity for vacuolating cytotoxin A (VacA), GroEL, FliD, H. pylori adhesin A (HpaA), and γ-glutamyl transpeptidase (gGT) was associated with a current infection with an area under the curve of 0.870 (95% CI: 0.837-0.903), which may help discriminate currently infected patients from eradicated ones (Model 2). DISCUSSION: The recomLine assay is sensitive and specific in determining H. pylori infection and eradication status and thus represents a valuable tool in the management of H. pylori infection.

Intraprocedural gastric juice analysis as compared to rapid urease test for real-time detection of Helicobacter pylori.

BACKGROUND: Endofaster is an innovative technology that can be combined with upper gastrointestinal endoscopy (UGE) to perform gastric juice analysis and real-time detection of Helicobacter pylori (H. pylori). AIM: To assess the diagnostic performance of this technology and its impact on the management of H. pylori in the real-life clinical setting. METHODS: Patients undergoing routine UGE were prospectively recruited. Biopsies were taken to assess gastric histology according to the updated Sydney system and for rapid urease test (RUT). Gastric juice sampling and analysis was performed using the Endofaster, and the diagnosis of H. pylori was based on real-time ammonium measurements. Histological detection of H. pylori served as the diagnostic gold standard for comparing Endofaster-based H. pylori diagnosis with RUT-based H. pylori detection. RESULTS: A total of 198 patients were prospectively enrolled in an H. pylori diagnostic study by Endofaster-based gastric juice analysis (EGJA) during the UGE. Biopsies for RUT and histological assessment were performed on 161 patients (82 men and 79 women, mean age 54.8 ± 19.2 years). H. pylori infection was detected by histology in 47 (29.2%) patients. Overall, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) for H. pylori diagnosis by EGJA were 91.5%, 93.0%, 92.6%, 84.3%, and 96.4%, respectively. In patients on treatment with proton pump inhibitors, diagnostic sensitivity was reduced by 27.3%, while specificity and NPV were unaffected. EGJA and RUT were comparable in diagnostic performance and highly concordant in H. pylori detection (κ-value = 0.85). CONCLUSION: Endofaster allows for rapid and highly accurate detection of H. pylori during gastroscopy. This may guide taking additional biopsies for antibiotic susceptibility testing during the same procedure and then selecting an individually tailored eradication regimen.

The influence of gastric atrophy on Helicobacter pylori antibiotics resistance in therapy-naïve patients.

Background: Antibiotic susceptibility of Helicobacter pylori to antibiotics may vary among different niches of the stomach. The progression of chronic H. pylori gastritis to atrophy changes intragastric physiology that may influence selection of resistant strains. Aim: To study the antibiotic resistance of H. pylori taking the severity of atrophic gastritis in antrum and corpus into account. Methods: Helicobacter pylori-positive patients (n = 110, m = 32, mean age 52.6 ± 13.9 years) without prior H. pylori eradication undergoing upper gastrointestinal (GI) endoscopy for dyspeptic symptoms were included in a prospective study. Patients were stratified into three groups depending on the grade of atrophy: no atrophy (OLGA Stage 0), mild atrophy (OLGA Stage I-II) and moderate/severe atrophy (OLGA Stage III-IV). Two biopsies each from the antrum and the corpus and one from the angulus were taken and assessed according to the updated Sydney system. H. pylori strains were isolated from antrum and corpus biopsies and tested for antibiotic susceptibility (AST) for amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin by the agar dilution methods. A Chi-square test of independence with a 95% confidence interval was used to detect differences in the proportion of patients with susceptible and resistant H. pylori strains. Results: Among 110 patients, primary clarithromycin resistance (R) was 30.0%, both in the antrum and corpus; metronidazole resistance accounted for 36.4 and 34.5% in the antrum and corpus; and levofloxacin was 19.1 and 22.7% in the antrum and corpus, respectively. Resistance rates to amoxicillin, tetracycline, and rifampicin were below 5%. Dual antibiotic resistance rate was 21.8%, and triple resistance rate was 9.1%. There was a significant difference in the resistance rate distribution in antrum (p < 0.0001) and corpus (p < 0.0001). With increasing severity of atrophy according to OLGA stages, there was a significant increase in clarithromycin-R and metronidazole-R. Conclusion: In treatment-naïve patients, antibiotic resistance and heteroresistance were related to the severity of atrophy. The high clarithromycin resistance in atrophic gastritis suggests that H. pylori antibiotic susceptibility testing should always be performed in this condition before selecting the eradication regimen.

The Fear of Gastric Cancer in Patients with Dyspepsia: Challenge in Specialist Care Gastroenterology.

BACKGROUND: Dyspepsia is one of the most common complaints in gastroenterology. While its etiology is usually benign, rare cases of malignancy have to be identified. Individualized risk stratification is essential for cost-effective management of dyspepsia. Here, we discuss the challenges of investigating dyspepsia at the specialist level and provide a framework for rational workup and surveillance strategies. SUMMARY: Causes of dyspepsia can be functional or organic, including gastritis, peptic ulcers, or malignancy. H. pylori gastritis represents a specific entity of dyspepsia and increases the risk of gastric cancer. H. pylori eradication can improve symptoms in a subset of patients and reduce gastric cancer risk. In young patients without alarm features, malignancy is rare, and noninvasive testing for H. pylori is appropriate. In elder patients and those with alarm features, high-quality endoscopy is the method of choice to rule out malignancy. Advanced corpus-predominant atrophic gastritis with or without intestinal metaplasia represent precancerous lesions. KEY MESSAGES: Symptom assessment requires to distinguish dyspepsia of functional or organic origin. Risk stratification in dyspeptic patients is based on age, alarm features, and H. pylori status. Noninvasive test-and-treat is recommended in patients with low gastric cancer risk, while endoscopy is recommended in individuals at increased risk. H. pylori infection should be eradicated in order to obtain a symptomatic benefit and reduce gastric cancer risk. Advanced preneoplastic lesions require endoscopic surveillance.

Gut microbiota profiles and the role of anti-CdtB and anti-vinculin antibodies in patients with functional gastrointestinal disorders (FGID).

BACKGROUND: Distinct faecal microbiota profiles are reported to be associated with various subtypes of IBS. Circulating antibodies to cytolethal distending toxin B (CdtB) and vinculin are proposed as biomarkers to identify post-infectious IBS. The aim of our study was to analyse serum levels of anti-CdtB and anti-vinculin antibodies in patients with different functional gastrointestinal disorders (FGID) and their correlation with the composition of faecal microbiome. METHODS: The study cohort comprised 65 prospectively recruited individuals: 15 with diarrhoea-type-IBS (IBS-D), 13 with constipation-type-IBS (IBS-C), 15 with functional dyspepsia (FD) and 22 healthy controls. FGID subgroups were defined according to Rome III criteria. Serum levels of anti-CdtB and anti-vinculin antibodies were measured by ELISA. Faecal microbiome composition analysis and assessment of dysbiosis were performed by GA-map® Dysbiosis Test. RESULTS: Positivity rate either for anti-CdtB or anti-vinculin antibodies was higher in the IBS-C group (76.9%) compared to IBS-D (40.0%), FD (60%) and healthy (63.6%) groups. Dysbiosis was more frequent in subjects positive for anti-CdtB antibodies and in IBS-C patients, who showed an increased amount of opportunistic/pro-inflammatory bacteria and reduced gut protective bacteria. IBS-C patients showed a high inter-individual variation of bacterial communities compared to other FGID subgroups and healthy individuals, whereas microbial profiles of patients with IBS-D and FD were overlapping with those of healthy controls. No bacteria markers showed significant differences between FGID subgroups and healthy controls. CONCLUSION: Neither anti-CdtB/anti-vinculin antibodies nor faecal microbial profiles allowed to discriminate between specific FGID subgroups. Dysbiosis was more frequent in patients presenting with anti-CdtB antibodies and in IBS-C patients.

Effect of frequently prescribed drugs on gastric cancer risk.

Gastric cancer is the fifth leading cancer worldwide. Infection with Helicobacter pylori represents the major risk factor, but only a small fraction of infected individuals will develop neoplasia. The progression of advanced gastric lesions to cancer is influenced by characteristics of the bacterial strain, host genetic and environmental factors. Recently, the effect of medications on gastric cancer risk has gained interest, because many commonly prescribed drugs affect gastric homeostasis. While non-steroidal anti-inflammatory drugs (NSAIDs) are a frequent cause of gastric ulcer disease, low-dose aspirin has been propagated for chemoprevention of various tumour entities. Beneficial effects of cyclooxygenase-inhibition for gastric cancer prevention is plausible, but its clinical relevance remains unclear. Furthermore, anti-tumorous effects have been postulated for statins and metformin. On the contrary, proton pump inhibitors (PPIs), which are commonly used for prevention of gastric ulcers and bleeding, have been associated with an increased gastric cancer risk in large observational studies. Most of these observations still require confirmation in prospective controlled trials. NSAIDs, statins and metformin have also been investigated as concomitant cancer treatment, but studies did not show convincing results to date. Here, we review the available evidence and possible mechanisms for the role of PPIs, NSAIDs, statins and metformin in gastric carcinogenesis, and discuss possible implications for clinical practice.

Tuberculous perihepatic abscess and neurosarcoidosis: report of 2 uncommon manifestations of 2 common granulomatous diseases in 1 patient.

Infections caused by pathogens of the Mycobacterium tuberculosis complex, i. e., tuberculosis (TB), and the non-infectious, autoimmune disease sarcoidosis are among the most common granulomatous diseases worldwide. Typically, the lung is the primary site of infection and manifestation, respectively which makes the two diseases important differential diagnoses. Both diseases can affect virtually all organ systems, albeit with significantly lower incidence. CASE PRESENTATION: We report the case of a 50-year-old Indian man presenting with a tuberculous perihepatic abscess and a systemic inflammatory response after being diagnosed with neurosarcoidosis presenting as a single granuloma in the frontal lobe with lymphadenopathy in 2014. On day of admission the patient presented with right upper abdominal pain and fever for two weeks. With increased inflammatory parameters in serum and after finding of external CT images, a perihepatic abscess was suspected. This encapsulated cave was drained percutaneously under CT control. A high concentration of acid-fast rods was detected using ZN, PCR was positive for M. tuberculosis. Several samples of sputum and urine were microscopically negative but yielded growth of Mycobacteria after four weeks. DISCUSSION: This is a case presenting with two different granulomatous diseases, each of which manifested itself in an atypical form. The tuberculous liver abscess might either be explained as a flare-up of latent tuberculosis under azathioprine therapy or as a reinfection acquired during one of several visits in the high-prevalence country India. In addition, it must be discussed whether the cerebral granuloma in 2014 could have been an early stage of tuberculous granuloma. Sensitivity of ZN staining is significantly reduced in cerebral samples, and negative PCR-results might be due to low germ load or methodical issues, e. g., decreased sensitivity in formalin fixated samples.

Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract-evidence from next-generation sequencing studies.

BACKGROUND: Proton pump inhibitors (PPI) are widely used to treat acid-related disorders of the upper gastrointestinal tract. However, large observational studies have raised concerns about PPI-associated adverse events. In recent years, data from next-generation sequencing studies suggested that PPIs affect the composition of the intestinal microbiota, while a balanced gut microbiome is essential for maintaining health. AIM: To review the available evidence from next-generation sequencing studies on the effect of PPIs on the intestinal microbiome and to discuss possible implications of PPI-induced dysbiosis in health and disease. METHODS: A systematic review was conducted following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. A PubMed query yielded 197 results. 19 publications met the prespecified eligibility criteria. RESULTS: Twelve observational study cohorts with 708 PPI users and 11 interventional cohorts with 180 PPI users were included in the review. In most studies, PPI treatment did not affect microbiological richness and diversity, but was associated with distinct taxonomic alterations: In the upper gastrointestinal tract, PPI users showed overgrowth of orally derived bacteria, mostly Streptococcaceae (findings based on six independent cohorts with 126 PPI users). In faecal samples, PPIs increased multiple taxa from the orders Bacillales (eg, Staphylococcaceae), Lactobacillales (eg, Enterococcaceae, Lactobacillaceae, Streptococcaceae) and Actinomycetales (eg, Actinomycetaceae, Micrococcaceae), the families Pasteurellaceae and Enterobacteriaceae and the genus Veillonella. Taxa decreased by PPIs include Bifidobacteriaceae, Ruminococcaceae, Lachnospiraceae and Mollicutes (findings in faecal samples based on 19 independent cohorts with 790 PPI users). CONCLUSION: PPI use is associated with moderate alterations to upper and distal gut microbiota. The available data suggest that PPI-induced hypochlorhydria facilitates colonization of more distal parts of the digestive tract by upper gastrointestinal microbiota.

Helicobacter pylori eradication in dyspepsia: New evidence for symptomatic benefit.

A causal relationship between Helicobacter pylori (H. pylori) infection and functional dyspepsia (FD) is well established in a subset of infected patients. In the Kyoto and Maastricht/Florence consensus reports H. pylori-associated dyspepsia is defined as an independent entity distinct from FD. H. pylori eradication is therefore the most cost-effective approach for infected patients with dyspeptic symptoms and superior to other medical therapies, such as Proton Pump Inhibitors. The therapeutic gain of H.pylori eradication for symptom relief compared to other therapeutic options is significant with the number needed to benefit of 12. Furthermore H.pylori cures chronic gastritis except in severe cases of atrophic gastritis and may prevent severe complications attributable to the infection. Several pathophysiological mechanisms are suggested for the generation of symptoms and are related to the distinct topographic expression and degree of gastric inflammation as well as changes of gastric acid secretion, gastrointestinal motility and visceral hypersensitivity.