Diagnostic value associated with the combination of saliva pepsin and microorganisms in functional heartburn and gastroesophageal reflux disease.

Heartburn is a common symptom shared by both gastroesophageal reflux disease (GERD) and functional heartburn (FHB), which can make it challenging to differentiate between the two conditions. However, examining oral manifestations of GERD can be a cost-effective and readily available method to aid in this differentiation process. It may serve as a valuable tool in distinguishing GERD from FHB.

Investigating the causal relationship of gut microbiota with GERD and BE: a bidirectional mendelian randomization.

BACKGROUND: Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett's esophagus(BE) hasn't been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis. METHODS: Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE. RESULTS: 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01-1.17) and BE(OR = 1.388, 95%CI = 1.03-1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways. CONCLUSIONS: This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.

Causal effect between gut microbiota and gastroesophageal reflux disease: a bidirectional two-sample Mendelian randomization study.

Previous observational studies have found that the gut microbiota is closely related to the pathogenesis of gastroesophageal reflux disease (GERD), while their causal relationship is unclear. A two-sample multivariate Mendelian randomization analysis was implemented to estimate the causal effect of gut microbiota on GERD. The gut microbiota aggregated statistics were derived from a meta-analysis of the largest available genome-wide association studies (GWAS) conducted by the MiBioGen alliance ( n  = 13 266). GERD aggregated statistics were derived from published GWAS (129 080 cases and 473 524 controls). A bidirectional two-sample Mendelian randomization study was conducted to explore the causal relationship between gut microbiota and GERD using the inverse variance weighted (IVW), Mendelian randomization Egger, single model, weighted median, and weighted model. To verify the stability of the main results of Mendelian randomization analysis, we performed sensitivity analysis. Based on the results of IVW, we found that Anaerostipes was causally associated with an increased risk of GERD [odds ratio (OR): 1.09, P  = 0.018]. Eight gut microbiota taxa ( Actinobacteria, Bifidobacteriales, Bifidobacteriaceae, Clostridiales vadin BB60 group, Rikenellaceae, Lachnospiraceae UCG004, Methanobrevibacter , and unknown genus id.1000000073 ) are predicted to act causally in suppressing the risk of GERD ( P  < 0.05). In addition, reverse Mendelian randomization analyses revealed that the abundance of 15 gut microbiota taxon was found to be affected by GERD. No significant estimation of heterogeneity or pleiotropy is detected. Our study presents a complicated causal relationship between gut microbiota and GERD that offers guidance on the selection of appropriate probiotics as clinical interventions for GERD.

Beneficial Effect of Heat-Killed Lactic Acid Bacterium Lactobacillus johnsonii No. 1088 on Temporal Gastroesophageal Reflux-Related Symptoms in Healthy Volunteers: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study.

A randomized, placebo-controlled, double-blind, parallel-group clinical study was conducted to examine the effects of ingesting a heat-killed lactic acid bacterium, Lactobacillus johnsonii No. 1088 (LJ88) on temporal gastroesophageal reflux-related symptoms in healthy volunteers. A total of 120 healthy Japanese volunteers of both sexes, aged between 21 and 63 years, whose Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) total score was 8 or greater, but who were not diagnosed with functional dyspepsia according to the Rome IV classification, were enrolled. They were randomly assigned to either the LJ88 or placebo group and instructed to ingest the test food (1 billion heat-killed LJ88 or placebo) once a day for six weeks. Gastroesophageal reflux-related symptoms were evaluated using FSSG scores as a primary endpoint. The Gastrointestinal Symptoms Rating Scale (GSRS), stomach state questionnaire, and serum gastrin concentration were used as secondary endpoints. In the FSSG evaluation, the heartburn score was significantly improved at 6 weeks in the LJ88 group compared to the placebo group. No severe adverse events related to the test food were observed. In conclusion, daily ingestion of heat-killed LJ88 improved temporal heartburn symptoms in non-diseased individuals.

Effect of Lactobacillus reuteri NCIMB 30351 drops on symptoms of infantile functional gastrointestinal disorders and gut microbiota in early infants: Results from a randomized, placebo-controlled clinical trial.

Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, representing one of the causes of significant parental anxiety, lead to a significant strain on the healthcare resources. In this study, we aimed to evaluate the effects of Lactobacillus reuteri drops (L. reuteri NCIMB 30351) on the symptoms of infantile colic, constipation, diarrhea, and gastroesophageal reflux, as well as on the levels of intestinal microbiota in full-term newborns during the first months of life. A randomized, placebo-controlled, single-masked (blinded), post-marketing clinical study was conducted in two clinical units-Children's City Clinical Hospital of Moscow and Medical Center "St. Andrew's Hospitals-NEBOLIT" from March 2020 to May 2022 in 90 infants aged from 1 to 4 months (mean age (± SD) 12.3 ± 5.09 weeks; 53.3% females, 46.7% males). Patients with colic, regurgitation (single symptom or combination of several symptoms), and constipation or diarrhea were randomly allocated in two parallel arms to receive either 5 drops (2 × 108 colony forming unit) of L. reuteri NCIMB 30351 (n = 60) or masked placebo (n = 30) for 25 consecutive days. Two treatment arms had equal numbers of patients with constipation and diarrhea (n = 30 each). Daily crying times and their duration, evacuations, and regurgitations were recorded in a structured diary. The levels of gut microbiota were analyzed by deep sequencing of bacterial 16S rRNA gene. Infants with colic receiving supplementary L. reuteri NCIMB 30351 for 25 days had significant reduction in the numbers of colic (change from baseline - 6.3 (7.34) vs - 3.0 (7.29) in placebo, P < 0.05) and numbers of crying cases and mean duration of crying (decrease from baseline - 144 (70.7) minutes, lower in the diarrhea subgroup than in constipation infants, compared with - 80 (58.9) in placebo, P < 0.0001), as well as regurgitation numbers (decreased by - 4.8 (2.49) with L. reuteri vs - 3 (7.74) with placebo). We also observed increased numbers of evacuations in infants with constipation (L. reuteri 2.2 (2.4) vs 0.9 (1.06) in placebo, P < 0.05). There was a remarkable reduction of evacuations in infants with diarrhea, while not statistically significant. The analysis of bacterial 16S rRNA gene in the collected samples showed that L. reuteri positively influences the proportions of prevalent species, while it negatively affects both conditionally pathogenic and commensal microbes. Additional in vitro test for formation of Clostridium colonies in the presence of the probiotic demonstrated that L. reuteri effectively inhibits the growth of pathogenic Clostridium species. No adverse events were reported in this study.   Conclusion: The uptake of L. reuteri NCIMB 30351 leads to a significant reduction in the number of regurgitations, feeding-induced constipations, and diarrhea as well as mean daily numbers of crying and crying duration in infants during the first months of life. Our results suggest that L. reuteri NCIMB 30351 represents a safe and effective treatment for colic in newborns.  Trial registration: ClinicalTrials.gov : NCT04262648. What is Known: • Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, represent one of the causes of significant parental anxiety. • A number of studies have shown that both the composition and diversity of the intestinal microbiota play important roles in the development and function of the gastrointestinal tract. What is New: • The uptake of L. reuteri NCIMB 30351 leads to a significant reduction in the number of regurgitations, feeding-induced constipations, and diarrhea as well as mean daily numbers of crying and crying duration in infants during the first months of life. • L. reuteri positively influences the proportions of prevalent species, while it negatively affects both conditionally pathogenic and commensal microbes in gut microbiota.

Relationship between Helicobacter pylori Eradication and Barrett's Esophagus Elongation.

INTRODUCTION: Helicobacter pylori eradication therapy may worsen gastroesophageal reflux disease that is a significant risk factor for Barrett's esophagus. However, the relationship between eradication therapy and Barrett's esophagus remains controversial. This study evaluated the impact of Helicobacter pylori eradication on the lengthening of Barrett's esophagus. MATERIALS AND METHODS: We conducted a retrospective analysis of consecutive patients who successfully underwent Helicobacter pylori eradication between 2004 and 2017. Endoscopic images obtained before and after eradication therapy were compared for Barrett's esophagus length according to the Prague C&M criteria and the presence of reflux esophagitis based on the Los Angeles classification. RESULTS: A total of 340 patients were analyzed (mean age: 66.9 ± 12.9 years) for a median follow-up of 55 months (interquartile range: 29.8-89.3). At the initial endoscopic assessment, 187 patients (55%) had a hiatal hernia, and all patients had gastric atrophy (C-0 to I: 2%, C-II to III: 47%, O-I to III: 51%). Reflux esophagitis was detected in 7 patients (2%) before eradication and in 21 patients (6%) afterward, which was a significant increase (p = 0.007). Barrett's esophagus was identified in 69 patients (20%) before eradication, with a median length of C0M1. Elongation after treatment was observed in only 2 patients (0.6%). We observed no significant increase in either the prevalence (p = 0.85) or the median length (p = 0.5) of Barrett's esophagus. CONCLUSIONS: Only 0.6% of patients exhibited Barrett's esophagus lengthening after Helicobacter pylori eradication therapy, suggesting no significant impact of the treatment on the development or elongation of Barrett's esophagus.

SPECIFIC FEATURES OF THE ORAL MICROBIOME IN YOUNG CHILDREN WITH ARYNGOPHARYNGEAL REFLUX AND ITS ROLE THE DEVELOPMENT OF RECURRENT RESPIRATORY DISEASES.

OBJECTIVE: The aim: To examine the composition of the oral microbiome in young children with laryngopharyngeal reflux (LPR) and its role the development of recurrent respiratory diseases. PATIENTS AND METHODS: Materials and methods: There were examined 38 children with physiological gastroesophageal reflux (GER), 18 children with LPR who had a medical history of recurrent bronchitis and 17 healthy children (control group). The study included the collection of anamnesis, objective examination. The qualitative and quantitative microbial composition of the upper respiratory tract was performed obtained by oropharyngeal deep swab. Salivary pepsin level and IL-8 were determined by enzyme-linked immunosorbent assay. RESULTS: Results: This research showed significant alterations in the oral microbiome of patients with GER and LPR as compared to healthy control. We found that gram-negative microbiota such as Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris, Proteus spp. and Candida albicans were identified in children with GER and LPR compared to the healthy control. At the same time, the amount of such a representative of the normal microbiome as Streptococcus viridans in children with LPR was sharply reduced. There were established a much higher mean salivary pepsin level of the patients with LPR than in the GER and control group. We found the association between high pepsin levels, saliva IL-8 levels and frequency of respiratory pathology in children with LPR. CONCLUSION: Conclusions: Our study confirms that increased levels of pepsin in saliva are a risk factor for recurrent respiratory diseases in children with LPR.

Systematic assessment of environmental factors for gastroesophageal reflux disease: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND: Side effects of long-term acid suppression have increased the scholars' interest in nonpharmacologic intervention. AIMS: We summarized an umbrella review of the association between environmental factors and gastroesophageal reflux disease (GERD) and assessed their credibility. METHODS: We appraised systematic reviews and meta-analyses. For each meta-analysis, we considered the effect size, 95% confidence interval, the heterogeneity, small-study effects, P-value for excess significance and largest study significant, then we graded the evidence according to Assessment of Multiple Systematic Reviews and the GRADE assessment. RESULTS: 23 publications met the inclusion criteria (13 meta-analyses and 10 systematic reviews), which evaluated 24 environmental factors. Among observational studies, we identified 7 risk factors: overweight/obesity [GERD/erosive esophagitis (EE)/GERD symptom], central adiposity [EE], smoking [GERD], alcohol [GERD/EE/non-erosive reflux disease (NERD)], NSAID [GERD], coffee [EE], Helicobacter pylori eradication [EE], and 1 protective factor: physical activity [GERD], this was based on a suggestive evidence of credibility. Across intervention studies, we identified 1 risk factor-Helicobacter pylori eradication [GERD] and 1 protective factor-breathing exercises [GERD], evidence for both was low grade. CONCLUSIONS: We found varying levels of evidence for different environmental factors of GERD. None of them was proven to be convincing or highly recommended.

Presence of Gastric Pepsinogen in the Trachea Is Associated with Altered Inflammation and Microbial Composition.

Gastroesophageal reflux is a common gastrointestinal issue that can lead to aspiration and contribute to respiratory problems. Little is known about how reflux can alter the respiratory microenvironment. We aimed to determine if the presence of gastric pepsinogen in the trachea was associated with changes in the microbial and inflammatory microenvironment. A pediatric cohort at high risk of reflux aspiration was prospectively recruited, and the tracheal microenvironment was examined. Pepsinogen A3 (PGA3) and cytokines were measured. The microbiome (bacterial and fungal) was profiled using 16S rRNA and internal transcribed spacer 2 (ITS2) amplicon sequencing. Increased bacterial richness and an altered composition driven by an enrichment of Prevotella correlated with high PGA3 levels. Fungal richness increased with PGA3, with higher Candida relative abundances observed in a subset of samples with high PGA3 levels. Source tracking of tracheal microbial taxa against taxa from matched oral and gastric samples revealed a significantly greater contribution of oral than of gastric taxa with higher PGA3 levels. Tracheal cytokines were differentially produced when stratified according to PGA3, with higher levels of interleukin-1 (IL-1)-related cytokines and IL-8 being associated with high PGA3 levels. Network analysis across cytokine and microbiome measures identified relationships between IL-1-related proteins and microbial taxa, with the presence of respiratory issues associated with higher levels of IL-1ß, IP-10, and Prevotella In conclusion, PGA3 levels in the trachea are correlated with increases in specific microbial taxa and inflammatory molecules, with an increase in oral microbes with increasing PGA3.

Treatment of non-erosive reflux disease and dynamics of the esophageal microbiome: a prospective multicenter study.

Non-erosive reflux disease (NERD) pathogenesis has not been thoroughly evaluated. Here, we assessed the response of patients with NERD to proton pump inhibitor (PPI) therapy; changes in the microbiome and biologic marker expression in the esophageal mucosa were also evaluated. Patients with NERD (n = 55) received esomeprazole (20 mg) for eight weeks. The treatment response was evaluated at baseline, week four, and week eight. Esophageal mucosal markers and oropharyngeal and esophageal microbiomes were analyzed in patients who underwent upper gastrointestinal endoscopy at screening (n = 18). Complete and partial response rates at week eight were 60.0% and 32.7% for heartburn, and 61.8% and 29.1% for regurgitation, respectively. The expressions of several inflammatory cytokines, including IL-6, IL-8, and NF-κB, were decreased at week eight. Streptococcus, Haemophilus, Prevotella, Veillonella, Neisseria, and Granulicatella were prevalent regardless of the time-point (baseline vs. week eight) and organ (oropharynx vs. esophagus). The overall composition of oropharyngeal and esophageal microbiomes showed significant difference (P = 0.004), which disappeared after PPI therapy. In conclusion, half-dose PPI therapy for eight weeks could effectively control NERD symptoms. The expression of several inflammatory cytokines was reduced in the esophagus, and oropharyngeal and esophageal microbiomes in patients with NERD showed significant difference. However, the microbial compositions in the oropharynx and esophagus were not affected by PPI therapy in this study. Impact of PPI on the microbiome in patients with NERD should be more investigated in future studies.

Reconsidering the "protective" hypothesis of Helicobacter pylori infection in eosinophilic esophagitis.

Since its discovery, Helicobacter pylori (H. pylori) has attracted attention in the biomedical world with its numerous pathophysiologic implications, both gastrointestinal and systemic. Beyond its well-established carcinogenic properties, emerging evidence also supports "harmful" proinflammatory and neurodegenerative roles of H. pylori. On the other hand, H. pylori infection has been proposed to be "protective" against several diseases, such as asthma and gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) is a relatively new, allergen/immune-mediated disease, which has also been linked to these considerations. Main arguments are a postulated shift of immune responses by H. pylori from T helper 2 (TH 2) to TH 1 polarization, as well as a potential decline of the H. pylori burden with the dramatic parallel rise of ΕοΕ: a series of observational studies reported an inverse association. In this review, we counter these arguments by providing further epidemiological data, which point out that this generalization might be rather incomplete. We also discuss the limitations of the existing studies evaluating a possible association. Furthermore, we provide current evidence on common pathogenetic components, which share both entities. In summary, the claim that H. pylori is protective against EoE is rather incomplete, and further mechanistic studies are necessary to elucidate a possible association.

Comparison of the Microbiota and Inorganic Anion Content in the Saliva of Patients with Gastroesophageal Reflux Disease and Gastroesophageal Reflux Disease-Free Individuals.

The oral cavity is one of the most complex microbial environments; however, the complex nature of the salivary microbiota and the level of inorganic anions in the saliva of subjects with and without gastroesophageal reflux disease (GERD) are poorly understood. The primary goals of this pilot research were to assess differences in salivary bacterial community composition and inorganic anion concentrations between patients with GERD and GERD-free people. Thus, the salivary microbiota within both groups was dominated by these genera: Streptococcus, Prevotella, Porphyromonas, Veillonella, Neisseria, Haemophilus, Fusobacterium, Rothia, and Leptotrichia. However, the relative abundances of the genera Actinomyces, Atopobium, Stomatobaculum, Ruminococcaceae_[G-2], Veillonella, and Leptotrichia were significantly higher in the saliva samples of patients with GERD, while the genera Porphyromonas, Gemella, Peptostreptococcus, and Neisseria were less abundant in this group. The concentrations of chloride, phosphate, and sulphate ions in the human saliva varied among all subjects and sampling time. These results broaden our knowledge of the salivary microbial community composition and chemistry of saliva of patients with GERD and GERD-free individuals.

Physicians' adherence to management guidelines for H. pylori infection and gastroesophageal reflux disease: a cross-sectional study.

BACKGROUND: Primary care physicians (PCPs) play a pivotal role in the management of illnesses of the digestive tract. The study aim was to assess the adherence of PCPs to the guidelines on the management of Helicobacter pylori (H. pylori) infection and gastroesophageal reflux disease (GERD) in adults. METHODS: We conducted a cross-sectional study during March-July 2017 using the survey platform of Maccabi Healthcare Services in Israel. The study questionnaire assessed adherence to the Maastricht/Florence guidelines on H. pylori infection and the American College of Gastroenterology guidelines on the management of GERD. We sent the study questionnaires to a random sample of 610 PCPs via electronic mails. We contacted those who did not respond by telephone; eventually 180 physicians completed the survey. RESULTS: Ninety (50%) and 60 (36%) of the responders reported using professional guidelines for the diagnosis and management of H. pylori infection and GERD, respectively. Of the 180 participants, 153 (85%) reported referring patients with suspected peptic ulcer disease to H. pylori testing, 109 (61%) reported referring patients with unexplained iron deficiency anemia and 83 (46%) refer relatives of gastric cancer patients. In caring for young patients who have dyspepsia without alarm symptoms, 127 (74%) reported referral to a urea breath test for the diagnosis of H. pylori infection, and 136 (81%) referral to a specialist in gastroenterology if alarm symptoms present. Triple therapy with proton pump inhibitors/clarithromycin/amoxicillin or metronidazole was reported as first-line therapy by 141 (83%) participants. For GERD, 94-98% of the participants followed the appropriate recommendations. CONCLUSIONS: We identified gaps between the practices of PCPs and the guidelines on H. pylori infection management, while guidelines on GERD management are well adopted. Simplification of the guidelines and exploring barriers towards their implementation by PCPs is warranted.

Effect of Helicobacter pylori eradication on reflux esophagitis and GERD symptoms after endoscopic resection of gastric neoplasm: a single-center prospective study.

BACKGROUND: The association between Helicobacter pylori and reflux esophagitis (RE) remains controversial. This study aimed to prospectively evaluate the effect of H. pylori eradication on RE and gastroesophageal reflux (GERD) symptoms in H. pylori-positive patients who underwent endoscopic resection of gastric neoplasm. METHODS: Of the 244 patients enrolled in this study, 173 H. pylori-positive patients underwent follow-up at least once. We evaluated the prevalence of RE and GERD symptoms in these patients following H. pylori eradication. RESULTS: There were 75.7% (131/173), 78.6% (125/159), and 78.9% (105/133) subjects who were successfully eradicated after 6, 12, and 18-24 months, respectively. During the 2-year follow-up period, the eradication of H. pylori did not increase the incidence of RE (OR 0.93; 95% CI, 0.49-1.77, p = 0.828). H. pylori status was also not associated with the development of GERD symptoms (OR 1.12; 95% CI, 0.47-2.95, p = 0.721). In the univariate analysis for RE, present smoking history (OR 4.79; 95% CI 1.98-11.60, p = 0.001), present alcohol consumption history (OR 2.18; 95% CI 1.03-4.63, p = 0.041), and diabetes mellitus (OR 2.44; 95% CI 1.02-5.86, p = 0.045) were found to be associated with RE. Multivariate analysis showed that present smoking history (OR 4.54; 95% CI 1.84-11.02, p = 0.001) was a significant risk factor for RE. CONCLUSIONS: H. pylori eradication did not increase the incidence of RE or GERD symptoms in patients who underwent endoscopic resection of gastric neoplasm.

The effects of a multispecies synbiotic on microbiome-related side effects of long-term proton pump inhibitor use: A pilot study.

Side effects of proton pump inhibitors (PPI) can be linked to the changes in the intestinal microbiome that occur during therapy, especially in long-term users. Therefore, the microbiome might also be a key player in the reduction of PPI side effects. We tested the effects of a three-month intervention with a multispecies synbiotic on intestinal inflammation, gut barrier function, microbiome composition, routine laboratory parameters and quality of life in patients with long-term PPI therapy. Thirty-six patients received a daily dose of a multispecies synbiotic for three months and were clinically observed without intervention for another three months. After intervention 17% of patients reached normal calprotectin levels; the overall reduction did not reach statistical significance (-18.8 ng/mg; 95%CI: -50.5; 12.9, p = 0.2). Elevated zonulin levels could be significantly reduced (-46.3 ng/mg; 95%CI: -71.4; -21.2; p < 0.001). The abundance of Stomatobaculum in the microbiome was reduced and Bacillus increased during the intervention. Furthermore, albumin, alkaline phosphatase and thrombocyte count were significantly increased and aspartate transaminase was significantly decreased during intervention. Gastrointestinal quality of life showed significant improvements. In conclusion, microbiome-related side effects of long-term PPI use can be substantially reduced by synbiotic intervention. Further studies are warranted to optimize dosage and duration of the intervention.

Relationship of the Esophageal Microbiome and Tissue Gene Expression and Links to the Oral Microbiome: A Randomized Clinical Trial.

INTRODUCTION: Although the microbiome is altered in various esophageal diseases, there is no direct evidence for a link between the oral or esophageal microbiome and underlying esophageal tissue. Here, we aimed to address these gaps through use of an antimicrobial mouth rinse to modify the esophageal microbiome and tissue gene expression. METHODS: In this randomized controlled trial, patients scheduled to undergo endoscopy for clinical indications used chlorhexidine mouth rinse or no treatment for 2 weeks before endoscopy. Oral swabs and saliva were collected at baseline and at follow-up, and the esophagus was sampled on the day of endoscopy. The microbiome was analyzed by 16S rRNA gene sequencing, and esophageal tissue gene expression was ascertained by RNA-Seq. RESULTS: Twenty subjects were enrolled and included in the analyses. Within individuals, the oral and esophageal microbiome composition was significantly correlated. Chlorhexidine treatment associated with significant alterations to the relative abundance of several esophageal bacterial taxa, and to expression of genes in the esophagus including reductions in periostin, claudin-18, chemokines CXCL1 and CXCL13, and several members of the tumor necrosis factor receptor superfamily. A taxon in genus Haemophilus in the esophagus also associated with significant changes in tissue gene expression. DISCUSSION: The oral and esophageal microbiomes are closely related within individuals, and esophageal microbiome alterations correlate with tissue gene expression changes. The esophageal microbiome may act as an important cofactor that influences pathogenesis and outcomes of diseases such as eosinophilic esophagitis, gastroesophageal reflux, and Barrett's esophagus.

Eradication of Helicobacter Pylori Infections and GERD: A systematic review and meta-analysis.

BACKGROUND/AIMS: This study evaluates the association between the eradication of Helicobacter pylori (H. pylori) and gastroesophageal reflux disease (GERD). MATERIALS AND METHODS: Relevant studies were identified by conducting literature search in PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP databases. The prevalence rates of gastroesophageal reflux, heartburn, epigastric pain, and nausea were extracted from the identified research articles and were used in meta-analysis of relative risks (RR) to achieve an overall effect size of the relationship between H. pylori eradication and GERD. RESULTS: A total of 19 randomized controlled trials were included in this meta-analysis. The prevalence of gastroesophageal reflux was significantly higher in patients with H. pylori eradication compared with patients without it (RR: 1.54, 95% CI: 1.06-2.24; p=0.02). A subgroup analysis did not identify any significant difference in GERD prevalence in studies conducted outside China (RR: 1.62, 95% CI: 0.98-2.68) or in China (RR: 1.30, 95% CI: 0.76-2.22). There were no significant differences in heartburn (RR: 1.03, 95% CI: 0.88-1.20), epigastric pain (RR: 0.98, 95% CI: 0.13-7.56), or nausea (RR: 0.44, 95% CI: 0.07-2.72) risk between patients with and without H. pylori eradication. CONCLUSION: Eradication of H. pylori infection is found to be associated with GERD, although regional differences may exist in the prevalence. Well-designed studies especially those with stratification of patients' basic conditions are needed to seek refined evidence of the association between H. pylori eradication and the GERD.

A perspective on risk factors for esophageal adenocarcinoma: emphasis on Helicobacter pylori infection.

Gastroesophageal reflux disease (GERD) and the increasing rate of its associated complications, including esophageal adenocarcinoma (EAC), has stimulated a plethora of studies attempting to evaluate provocative and protective factors. Helicobacter pylori (Hp) infection (Hp-I) was initially considered as a beneficial condition in GERD management based on rather limited data. Large-scale regional studies revealed an alternative approach, by suggesting a positive relationship between Hp-I and EAC development. Regarding pathophysiology, Hp-I induces gastric microbiota disturbances through hypochlorhydria and chronic inflammation, with a subsequent possible effect on the GERD-Barrett's esophagus (BE)-EAC cascade. Additionally, both direct effects on esophageal mucosa and indirect effects on known mechanisms of GERD, such as acid pocket and transient lower esophageal sphincter relaxation, remain to be elucidated. Hp contribution to carcinogenesis is related to oncogenic gastrin, cyclooxygenase-2, and prostaglandins; Ki-67 is also expressed and represents an index of BE-related malignancy. Moreover, Hp-I is vigorously suggested as a risk factor for metabolic syndrome, which may be the link between Hp-I and EAC. Although further studies are necessary to establish a pathophysiologic risk between Hp-I and the GERD-BE-EAC sequence, the theory of Hp protection against GERD seems outdated.

Aerodigestive sampling reveals altered microbial exchange between lung, oropharyngeal, and gastric microbiomes in children with impaired swallow function.

BACKGROUND: Children with oropharyngeal dysphagia have impaired airway protection mechanisms and are at higher risk for pneumonia and other pulmonary complications. Aspiration of gastric contents is often implicated as a cause for these pulmonary complications, despite being supported by little evidence. The goal of this study is to determine the relative contribution of oropharyngeal and gastric microbial communities to perturbations in the lung microbiome of children with and without oropharyngeal dysphagia and aspiration. METHODS: We conducted a prospective cohort study of 220 patients consecutively recruited from a tertiary aerodigestive center undergoing simultaneous esophagogastroduodenoscopy and flexible bronchoscopy. Bronchoalveolar lavage, gastric and oropharyngeal samples were collected from all recruited patients and 16S sequencing was performed. A subset of 104 patients also underwent video fluoroscopic swallow studies to assess swallow function and were categorized as aspiration/no aspiration. To ensure the validity of the results, we compared the microbiome of these aerodigestive patients to the microbiome of pediatric patients recruited to a longitudinal cohort study of children with suspected GERD; patients recruited to this study had oropharyngeal, gastric and/or stool samples available. The relationships between microbial communities across the aerodigestive tract were described by analyzing within- and between-patient beta diversities and identifying taxa which are exchanged between aerodigestive sites within patients. These relationships were then compared in patients with and without aspiration to evaluate the effect of aspiration on the aerodigestive microbiome. RESULTS: Within all patients, lung, oropharyngeal and gastric microbiomes overlap. The degree of similarity is the lowest between the oropharynx and lungs (median Jensen-Shannon distance (JSD) = 0.90), and as high between the stomach and lungs as between the oropharynx and stomach (median JSD = 0.56 for both; p = 0.6). Unlike the oropharyngeal microbiome, lung and gastric communities are highly variable across people and driven primarily by person rather than body site. In patients with aspiration, the lung microbiome more closely resembles oropharyngeal rather than gastric communities and there is greater prevalence of microbial exchange between the lung and oropharynx than between gastric and lung sites (p = 0.04 and 4x10-5, respectively). CONCLUSIONS: The gastric and lung microbiomes display significant overlap in patients with intact airway protective mechanisms while the lung and oropharynx remain distinct. In patients with impaired swallow function and aspiration, the lung microbiome shifts towards oropharyngeal rather than gastric communities. This finding may explain why antireflux surgeries fail to show benefit in pediatric pulmonary outcomes.