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Objective: To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis ) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods: A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis +celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results: At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P ＜0.05) and mild/moderate dysplasia (median 2.00, P ＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2 ), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P ＜0.05), and mild/moderate dysplasia (median 1.00, P ＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions: P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.

Change in mucosal microbiome is associated with various types of cancer in digestive tract. We hypothesized that microbial communities in the esophageal endoscopic wash fluids reflects resident flora in esophageal mucosa that is associated with esophageal carcinoma (EC) risk and/or directly correlates microbiome derived from EC tumor tissue. Studying microbial communities in esophageal endoscopic wash samples would be therefore useful to predict the incidence or risk of EC. We examined microbial communities of the endoscopic wash samples from 45 primary EC and 20 respective non-EC controls using 16S rRNA V3-V4 amplicon sequencing. The result was also compared with microbial communities in matched endoscopic biopsies from EC and non-cancerous esophageal mucosa. Compared with non-EC controls, 6 discriminative bacterial genera were detected in EC patients. Among them, relative abundance ratio of Prevotella and Shuttlewarthia, as well as decrease of genus Prevotella presented good prognostic performance to discriminate EC from controls (area under curve, 0.86, 0.82, respectively). Multivariate analysis showed occurrence of EC was an independent factor associated with decrease of this bacteria. Abundance of genus Prevotella in the esophageal endoscopic wash samples was significantly correlated with the abundance of this bacteria in the matched endoscopic biopsies from non-cancerous esophageal mucosa but not in the EC tissues. Our findings suggest that microbiome composition in the esophageal endoscopic wash samples reflects resident flora in the esophagus and significantly correlates with the incidence of EC., (© 2024. The Author(s).)

Esophageal cancer (EC) is a multifaceted disease. Our understanding of the involvement of esophageal microbiota in its pathogenesis and progression is limited, which is due to the lack of proper endoscopic sampling methods. Hereby, we conducted a comparative analysis of paired samples obtained through endoscopic brushing and cytosponge, aiming at assessing the feasibility of using cytosponge as a minimally invasive sampling way for studying esophageal microbiota. Our findings suggest that cytosponge sampling yielded significantly superior community richness and diversity compared to endoscopic brushing in both controls (non-cancerous) and EC individuals. The analysis of beta-diversity revealed distinct microbial community pattern in the genus diversity between the two sampling methods, underscoring the importance of selecting appropriate sampling methods to effectively characterize the esophageal microbiota. Specifically, Lactococcus and Serratia showed higher abundance in the samples collected by endoscopic brushing, while Alloprevotella and Leptotrichia were more enriched in the samples collected by cytosponge. These differences in dominant microbes were associated with metabolic pathways that particularly were related to host inflammation, such as pyruvate and glucose metabolisms. Notably, the phylogenetic levels of the microbiota indicated varied explanatory power for different detection purposes. This study underscores the substantial impact of sampling method selection on the acquisition of esophageal microbiota associated with the EC development, encompassing considerations of both abundance and diversity. This highlights the significance of selecting an appropriate sampling method for investigating the esophageal microbial status and studying the micro-environment in EC-related individuals., Importance: This study addresses a critical issue in esophageal cancer study by comparing two different sampling methods, endoscopic brushing and cytosponge, for investigating the esophageal microbiota. Our work highlights the suitability of the cytosponge technique as a minimally invasive sampling method for studying the esophageal microbiota and emphasizes the importance of selecting an appropriate sampling method to characterize the microbial community. Our findings have significant implications for advancing the understanding of the role of the esophageal microbiota in cancer development and will inform future research and clinical approaches in this field., Competing Interests: The authors declare no conflict of interest.

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., (© 2024 S. Karger AG, Basel.)

Oesophageal cancer is the most common gastrointestinal malignancy in China and one of the major causes of death due to cancer worldwide. The occurrence of oesophageal cancer is a multifactor, multistage, and multistep process influenced by heredity, the environment, and microorganisms. Specifically, bacterial infection may be involved in the process of tissue carcinogenesis by directly or indirectly influencing tumour occurrence and development. Porphyromonas gingivalis is an important pathogen causing periodontitis, and periodontitis can promote the occurrence of various tumours. An increasing number of studies to date have shown that P. gingivalis plays an important role in the occurrence and development of oesophageal cancer. Overall, exploring how P. gingivalis promotes oesophageal cancer occurrence and development and how it affects the prognosis of these patients is of great importance for the diagnosis, prevention, and treatment of this type of cancer. Herein, the latest progress is reviewed.

Background & Aims: Microbiota composition and mechanisms of host-microbiota interactions in the esophagus are unclear. We aimed to uncover fundamental information about the esophageal microbiome and its potential significance to eosinophilic esophagitis (EoE)., Methods: Microbiota composition, transplantation potential, and antibiotic responsiveness in the esophagus were established via 16S ribosomal RNA sequencing. Functional outcomes of microbiota colonization were assessed by RNA sequencing analysis of mouse esophageal epithelium and compared with the human EoE transcriptome. The impact of dysbiosis was assessed using a preclinical model of EoE., Results: We found that the murine esophagus is colonized with diverse microbial communities within the first month of life. The esophageal microbiota is distinct, dominated by Lactobacillales, and demonstrates spatial heterogeneity as the proximal and distal esophagus are enriched in Bifidobacteriales and Lactobacillales, respectively. Fecal matter transplantation restores the esophageal microbiota, demonstrating that the local environment drives diversity. Microbiota colonization modifies esophageal tissue morphology and gene expression that is enriched in pathways associated with epithelial barrier function and overlapping with genes involved in EoE, including POSTN, KLK5, and HIF1A. Finally, neonatal antibiotic treatment reduces the abundance of Lactobacillales and exaggerates type 2 inflammation in the esophagus. Clinical data substantiated loss of esophageal Lactobacillales in EoE compared with controls., Conclusions: The esophagus has a unique microbiome with notable differences between its proximal and distal regions. Fecal matter transplantation restores the esophageal microbiome. Antibiotic-induced dysbiosis exacerbates disease in a murine model of EoE. Collectively, these data establish the composition, transplantation potential, antibiotic responsiveness, and host-microbiota interaction in the esophagus and have implications for gastrointestinal health and disease., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in China. The role of the bacteria present in ESCC tissue in neoplastic progression has not been fully elucidated. This study aimed to uncover different bacterial communities in ESCC tissues and examine the correlation between the abundance of the esophageal flora and clinicopathologic characteristics of ESCC., Results: Microorganisms in tumors and normal tissues showed obvious clustering characteristics. The abundance of Fusobacterium (P = 0.0052) was increased in tumor tissues. The high level of Fusobacterium nucleatum was significantly associated with pT stage (P = 0.039) and clinical stage (P = 0.0039). The WES data showed that COL22A1, TRBV10-1, CSMD3, SCN7A and PSG11 were present in only the F. nucleatum-positive ESCC samples. GO and protein domain enrichment results suggested that epidermal growth factor might be involved in the regulation of cell apoptosis in F. nucleatum-positive ESCC. Both a higher mutational burden and F. nucleatum-positive was observed in tumors with metastasis than in tumors without metastasis., Conclusion: F. nucleatum is closely related to the pT stage and clinical stage of ESCC. The abundance of F. nucleatum and tumor mutation burden may be used in combination as a potential method to predict metastasis in ESCC., (© 2021. The Author(s).)

The aim of this study was to clarify risk factors for esophageal candidiasis (EC) in immunocompetent patients in a community hospital. 7736 patients who underwent esophagogastroduodenoscopy at our hospital from April 2012 to July 2018 were enrolled. The relationships between EC and the following factors: age, gender, body mass index, lifestyle, lifestyle-related diseases, medication, and endoscopic findings were analyzed. EC was observed in 184 of 7736 cases (2.4% morbidity rate). Multivariate analysis revealed that significant risk factors for the development of EC were: diabetes mellitus {odds ratio (OR): 1.52}, proton pump inhibitor (PPI) use (OR: 1.69), atrophic gastritis (AG) (OR: 1.60), advanced gastric cancer (OR: 4.66), and gastrectomy (OR: 2.32). When severe EC (Kodsi grade ≥ II) was compared to mild EC (grade I), the most significant risk factors were advanced gastric cancer (OR: 17.6) and gastrectomy (OR: 23.4). When considering the risk of AG and PPI use with EC development, the risk increased as follows: AG (OR: 1.59), PPI use (OR: 2.25), and both (OR: 3.13). PPI use, AG, advanced gastric cancer and post-gastrectomy are critical risk factors for the development of EC. We suggest close monitoring for EC development when PPIs are administered to patients with these factors., (© 2021. The Author(s).)

Background: The enrichment of Gram-negative bacteria of oral origin in the esophageal microbiome has been associated with the development of metaplasia. However, to date, no study has comprehensively assessed the relationships between the esophageal microbiome and the host., Methods: Here, we examine the esophageal microenvironment in gastro-esophageal reflux disease and metaplasia using multi-omics strategies targeting the microbiome and host transcriptome, followed by targeted culture, comparative genomics, and host-microbial interaction studies of bacterial signatures of interest., Results: Profiling of the host transcriptome from esophageal mucosal biopsies revealed profound changes during metaplasia. Importantly, five biomarkers showed consistent longitudinal changes with disease progression from reflux disease to metaplasia. We showed for the first time that the esophageal microbiome is distinct from the salivary microbiome and the enrichment of Campylobacter species as a consistent signature in disease across two independent cohorts. Shape fitting and matrix correlation identified associations between the microbiome and host transcriptome profiles, with a novel co-exclusion relationship found between Campylobacter and napsin B aspartic peptidase. Targeted culture of Campylobacter species from the same cohort revealed a subset of isolates to have a higher capacity to survive within primary human macrophages. Comparative genomic analyses showed these isolates could be differentiated by specific genomic features, one of which was validated to be associated with intracellular fitness. Screening for these Campylobacter strain-specific signatures in shotgun metagenomics data from another cohort showed an increase in prevalence with disease progression. Comparative transcriptomic analyses of primary esophageal epithelial cells exposed to the Campylobacter isolates revealed expression changes within those infected with strains with high intracellular fitness that could explain the increased likelihood of disease progression., Conclusions: We provide a comprehensive assessment of the esophageal microenvironment, identifying bacterial strain-specific signatures with high relevance to progression of metaplasia., (© 2021. The Author(s).)

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory esophageal disease triggered by food antigens. Cumulative evidence supports the implication of microbiota and the innate immune system in the pathogenesis of EoE. Changes in the esophageal microbiome were investigated by applying 16S rRNA gene sequencing on esophageal biopsies of adult patients with active EoE at baseline (n = 30), and after achieving remission with either proton pump inhibitors (PPI, n = 10), swallowed topical corticosteroids (STC, n = 10) or food-elimination diets (FED, n = 10). Ten non-EoE biopsies were also characterized as controls. Compared to controls, no differences in alpha (intra-sample) diversity were found in EoE microbiota overall. However, it decreased significantly among patients who underwent FED. As for beta (inter-sample) diversity, non-EoE controls separated from EoE baseline samples. Post-treatment samples from patients treated with PPI and FED had a more similar microbiota composition, while those receiving STC were closer to controls. Differential testing of microbial relative abundance displayed significant changes for Filifactor, Parvimonas and Porphyromonas genera. Analysis of predicted functions indicated alterations in metabolic pathways and abundance of sulphur-cytochrome oxidoreductases. Our findings demonstrate changes in microbiota associated with EoE, as well as a treatment effect on the microbiome.

Background/aims: Patients with achalasia have a high incidence of esophageal squamous cell carcinoma (ESCC), which may be associated with alterations in oral and esophageal microbiota caused by food stasis. This study compared the oral and esophageal microbiota of patients with achalasia before and after peroral endoscopic myotomy (POEM). It also compared patients with achalasia to those with ESCC., Materials and Methods: The study prospectively examined 6 patients with achalasia and 14 with superficial ESCC. Oral samples obtained from the buccal mucosa using a swab and esophageal samples obtained from the mid-esophagus using a brush via endoscopy were analyzed by 16S rRNA metagenome sequencing. Additionally, endoscopic and histological findings of patients with achalasia before and after POEM were prospectively compared., Results: In patients with achalasia, Streptococcus was most abundant in both the oral and the esophageal microbiota, and these microbiota were significantly different. Although the overall structure of the oral and esophageal microbiota did not change after POEM, the relative abundance rate of Haemophilus and Neisseria increased in the esophagus, and endoscopic findings of inflammation improved after POEM (P = .04). The relative abundance of microbiota was not different among patients with achalasia from those with ESCC., Conclusions: The oral and esophageal microbiota were significantly different in patients with achalasia, and some of the composition of the esophageal microbiota changed after POEM. However, these findings and disease-specific microbiota should be further evaluated in large-scale studies.

The diverse human gut microbiome is comprised of approximately 40 trillion microorganisms representing up to 1000 different bacterial species. The human microbiome plays a critical role in gut epithelial health and disease susceptibility. While the interaction between gut microbiome and gastrointestinal pathology is increasingly understood, less is known about the interaction between the microbiome and the aerodigestive tract. This review of the microbiome of the aerodigestive tract in health, and alterations in microbiome across esophageal pathologies highlights important findings and areas for future research. First, microbiome profiles are distinct along the aerodigestive tract, spanning the oral cavity to the stomach. In patients with reflux-related disease such as gastro-esophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma, investigators have observed an overall increase in gram negative bacteria in the esophageal microbiome compared to healthy individuals. However, whether differences in microbiome promote disease development, or if these shifts are a consequence of disease remains unknown. Interestingly, use of proton pump inhibitor therapy is also associated with shifts in the microbiome, with distinct shifts and patterns along the aerodigestive tract. The relationship between the human gut microbiome and esophageal pathology is a ripe area for investigation, and further understanding of these pathways may promote development of novel targets in prevention and therapy for esophageal diseases.

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.

Preliminary studies suggested a possible correlation of microbiota with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), where the need for tools to ameliorate its poor prognosis is mandatory. We explored the potential signature of esophageal microbiota and its predicted functional profile along the continuous spectrum from BE to EAC. We analyzed through 16S-based amplicon sequencing the mucosal microbiota and the microbiota-related functional predictions in 10 BE and 6 EAC patients compared with 10 controls, exploring also potential differences between the metaplastic mucosa (BEM) and the adjacent normal areas of BE patients (BEU). BEM and EAC showed a higher level of α and β-diversity. BEM evidenced a decrease of Streptococcus and an increase of Prevotella, Actinobacillus, Veillonella, and Leptotrichia. EAC displayed a striking reduction of Streptococcus, with an increase of Prevotella, Veillonella and Leptotrichia. LefSe analysis identified Leptotrichia as the main taxa distinguishing EAC. BEM showed a decreased α-diversity compared with BEU and a reduction of Bacteroidetes, Prevotella and Fusobacterium. Functional predictions identified peculiar profiles for each group with a high potential for replication and repair in BEM; an upregulated energy, replication and signaling metabolisms, with the fatty-acids biosynthesis and nitrogen and D-alanine pathways down-regulated in EAC. Our pilot study identifies a unique microbial structure and function profile for BE and EAC, as well as for metaplastic and near-normal areas. It proposes a new concept for BE, which could be intended not only as the histological, but, also, as the microbial closest precursor of EAC. This requires further larger follow-up studies, but opens intriguing horizons towards innovative diagnostic and therapeutic options for EAC., Competing Interests: The authors have declared that no competing interests exist.

Aims: Distinguishing true oesophageal Candida infections from oral contaminants is a common diagnostic issue. Historically, histological features believed to indicate true infection included epithelial invasion by pseudohyphae and intraepithelial neutrophils. Whether or not these features correlate with endoscopic lesions, symptoms and response to therapy has never been tested in a large cohort. The aim of this study was to determine whether specific histological features correlate with clinical and endoscopic findings when Candida is found in oesophageal biopsies., Methods and Results: We reviewed 271 biopsies in which Candida was detected. Cases were evaluated for the presence of desquamated epithelial cells, location/type of fungal forms, neutrophils, and ulceration. Medical records were reviewed for clinical history, endoscopic lesions, and response to antifungal therapy. Statistical analysis was used to determine whether any histological features significantly correlated with clinical variables. There were 120 males and 151 females with a mean age of 42 years. Fifty-nine per cent had symptoms referable to the oesophagus, particularly dysphagia (36%). Most (73%) patients had abnormal endoscopic findings, with plaques, ulcers, or macroscopic evidence of oesophagitis. Seventy-one per cent of patients with documented antifungal therapy showed symptomatic improvement. Overall, there was no statistically significant correlation between any histological feature and presenting symptoms, endoscopic findings, or response to therapy. Importantly, the lack of pseudohyphae, demonstrable invasion of intact epithelium or neutrophilic infiltrates did not exclude clinically significant infection., Conclusions: We conclude that detection of Candida in oesophageal biopsies is always potentially clinically significant. Treatment decisions should be made on the basis of an integration of clinical, endoscopic and histological findings., (© 2020 John Wiley & Sons Ltd.)

Sarcina species are anaerobic gram-positive cocci rarely seen in the upper gastrointestinal tract and associated with delayed gastric emptying. We present 3 cases of Sarcina infection with varying clinical presentations including the first reported case of Sarcina in a patient with eosinophilic esophagitis. Although the pathogenesis of Sarcina is unclear, awareness of the bacteria is important as they can usually only be detected on histopathologic examination of upper gastrointestinal biopsies. Treatment in symptomatic patients may prevent severe complications such as emphysematous gastritis and gastric perforation.

The microflora of 64 biopsies taken during fibrogastroduodenoscopy of the mucous membrane of the esophagus, stomach and duodenum in healthy volunteers and 1120 samples obtained from the same parts of the digestive tract in patients with esophagitis, chronic gastritis and peptic ulcer disease were studied. The patients ranged in age from 18 to 62 years. Traditional bacteriological method was used to isolate and identify microorganisms. Staphylococcus spp., Streptococcus spp., Lactobacillus spp., Bacteroides spp., Stomatococcus spp., Enterobacteriaceae, Corynebacterium spp., Micrococcus spp., Neisseria spp., Veilonella spp. were isolated from biopsies of healthy respondents in an average amount from 3.2 to 4.68 lg CFU/g. H.pylori was found in 60% (5.66 lg CFU/g) in the esophagus, in 33.3% of cases (5.12 lg CFU/g) from the fundal part of the stomach, in 44.4% (5.25 lg CFU/g) from the antral part of the stomach, in 5.5% (4.2 lg CFU/g) in the duodenal mucosa. In samples obtained from the inflamed and eroded mucous membrane of the esophagus, stomach and duodenum, opportunistic bacteria of the genera Klebsiella, Enterobacter, Proteus, Pseudomonas, Peptococcus, Actinomyces, yeast fungi of the genus Candida etc. were detected in an amount exceeding 4 lg CFU/g. H. pylori isolated in 6.3-16.7% of patients (4.25-4.6 lg CFU/g) and did not dominate in relation to other microorganisms, and in most cases had a low frequency of its occurrence. In patients with the recurrence of peptic ulcer disease, exacerbation of chronic gastritis and esophagitis, dysbiosis was developed, characterized by an increase in the species and quantitative composition of opportunistic microflora, an increase in its enzymatic and cytotoxic activity, which can contribute to the maintenance of inflammatory and necrotic processes and inhibit the elimination of the pathological process., Competing Interests: The authors declare no conflict of interest.

Purpose: Emerging evidence indicates that gut microbiome plays a crucial role in the cancer pathogenesis. Although Fusobacterium nucleatum ( F. nucleatum ) is associated with poor prognosis in multiple cancers, its clinical significance in predicting response to chemotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains unclear., Experimental Design: The F. nucleatum levels were quantified by qPCR assays in tumor tissues from 551 patients with ESCC from two independent cohorts, including 101 patients who received neoadjuvant chemotherapy prior to curative resection. Associations between F. nucleatum burden and recurrence-free survival (RFS), as well with chemotherapeutic response were evaluated using response evaluation criteria in solid tumors (RECISTs), primary tumor metabolic response defined by maximum standardized uptake value (SUV max ) changes in positron emission tomography-CT (PET/CT), and pathologic tumor regression grade (TRG)., Results: High burden of F. nucleatum in patients with ESCC associated with poor RFS in both training [log-rank P = 0.02; HR = 1.61; P = 0.03] and validation cohorts (log-rank P = 0.003; HR = 1.96; P = 0.004). Importantly, patients with ESCC with high levels of F. nucleatum displayed poor chemotherapeutic response for all three evaluation methods: RECIST ( P = 0.04), SUV max change in PET/CT ( P = 0.0004), and TRG ( P = 0.003)., Conclusions: We conclude that high levels of intratumoral F. nucleatum have a prognostic significance for predicting poor RFS in patients with ESCC. More importantly, our data indicates that higher F. nucleatum burden correlates with poor response to neoadjuvant chemotherapy, suggesting the possibility that an antibiotic intervention against this bacterium may significantly improve therapeutic response in patients with ESCC., (©2019 American Association for Cancer Research.)

Background & Aims: Previous or current infection with Helicobacter pylori (exposure) has been reported to protect against eosinophilic esophagitis (EoE), perhaps owing to H pylori-induced immunomodulation. However, findings vary. We performed a systematic review and meta-analysis of comparative studies to define the association between H pylori exposure and EoE more clearly., Methods: We searched 4 large databases to identify comparative clinical studies that included sufficient detail to determine the odds or risk of EoE (primary outcome) or esophageal eosinophilia (secondary outcome) among individuals exposed to H pylori (exposed) vs individuals who were tested and found to be unexposed. Estimates were pooled using a random-effects model. Meta-regression and sensitivity analyses were planned a priori. Studies were evaluated for quality, risk of bias, publication bias, and heterogeneity., Results: We analyzed 11 observational studies comprising data on 377,795 individuals worldwide. H pylori exposure vs nonexposure was associated with a 37% reduction in odds of EoE (odds ratio, 0.63; 95% CI, 0.51-0.78) and a 38% reduction in odds of esophageal eosinophilia (odds ratio, 0.62; 95% CI, 0.52-0.76). Fewer prospective studies found a significant association between H pylori exposure and EoE (P = .06) than retrospective studies. Effect estimates were not affected by study location, whether the studies were performed in pediatric or adult populations, time period (before vs after 2007), or prevalence of H pylori in the study population., Conclusions: In a comprehensive meta-analysis, we found evidence for a significant association between H pylori exposure and reduced odds of EoE. Studies are needed to determine the mechanisms of this association., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The role of gut microbes in health and disease has often been surmised from stool, which is easily sampled and rich in microbial diversity, density, and abundance. Microbial analyses of stool have been accepted as measures to determine the relationship of gut microbiomes with host health and disease, based on the belief that it represents all microbial populations throughout the gut. However, functional heterogeneity of each gastrointestinal tract (GIT) segment gives rise to regional differences in gut microbial populations. Herein, we summarize the literature regarding the microbial landscape along the rostral to caudal, i.e., horizontal mouth to anus, axis of the GIT. We aim to identify gaps in the literature, particularly regarding small intestinal microbiota abundance and diversity, highlight the importance of regional microbiota on host health and disease, as well as discuss opportunities to advance this line of research., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Esophagus, as the pipe connecting oral cavity and stomach, has unique anatomical structure and physiological functions. The related diseases including esophageal cancer and precancerous lesions are the ones of major public health problems in China. The pathogenesis of esophageal diseases is still not clear. The exploration of correlation between the changes of esophageal microbiota and esophageal diseases becomes a new breakthrough in the study of etiology. Previous studies have found enrichment of gram-positive bacteria in the normal esophagus, while a decrease in diversity of bacteria and a dominant gram-negative anaerobe in diseased esophagus. Although much progress has been made in the study of esophageal microbiota, the standard method of how to accurately and noninvasively collect esophageal microbiota is still lack, which is an important part of the esophageal microbial research.

Purpose of Review: There has been an exponential increase in the incidence of esophageal adenocarcinoma (EAC) over the last half century. Barrett's esophagus (BE) is the only known precursor lesion of EAC. Screening for BE in high-risk populations has been advocated with the aim of identifying BE, followed by endoscopic surveillance to detect dysplasia and early stage cancer, with the intent that treatment can improve outcomes. We aimed to review BE screening methodologies currently recommended and in development., Recent Findings: Unsedated transnasal endoscopy allows for visualization of the distal esophagus, with potential for biopsy acquisition, and can be done in the office setting. Non-endoscopic screening methods being developed couple the use of swallowable esophageal cell sampling devices with BE specific biomarkers, as well as trefoil factor 3, methylated DNA markers, and microRNAs. This approach has promising accuracy. Circulating and exhaled volatile organic compounds and the foregut microbiome are also being explored as means of detecting EAC and BE in a non-invasive manner. Non-invasive diagnostic techniques have shown promise in the detection of BE and may be effective methods of screening high-risk patients.

The role of the microflora in the development of esophageal disease is still largely unknown and is being investigated in more detail. Our goal was to determine how the microbiota levels of endoscope and uvular swabs compared to the levels of tissue biopsies along various points of the esophagus. 17 patients with Barrett's esophagus agreed to participate in the study. Biopsies of esophageal mucosa were taken from the (1) proximal esophagus, (2) mid-esophagus, (3) distal esophagus, and (4) Barrett's esophagus. Swabs were also taken from the uvula and the endoscope. Throughout the esophagus, 17 bacterial genera were detected from the samples. The microflora pattern obtained from the uvula and endoscopic swabs did not correlate well with mucosal biopsies along any aspect of the esophagus. There were statistically significant differences in the levels and proportions of bacteria found when comparing the uvula swab to the esophageal biopsies and when comparing the endoscope swab to the esophageal biopsies. Obtaining a simple swab of the uvula or endoscope itself appears to be a poor substitute for tissue biopsy of esophageal mucosa when evaluating microflora patterns. When performing microflora studies of the esophagus, mucosal biopsies should be used for analysis.

Aims: The purpose of this study is to compare distal oesophagus of persons with and without gastric reflux in terms of bacterial load and presence of certain bacterial species., Methods and Results: Two biopsy specimens were obtained from the distal oesophagus at 5 cm above the gastroesophageal junction of each of the 50 patients (20 with normal oesophagus and 30 with reflux oesophagitis) under endoscopic examination and used for histological examination and DNA isolation. We used a real-time PCR-based assay to quantify the bacterial load and the presence of certain bacterial species from one of the biopsy samples. The biopsy specimens taken from the patients with reflux oesophagitis were consistent with gastroesophageal reflux disease (GERD). The bacterial load did not significantly differ between the groups (P < 0·005)., Conclusion: While there was no difference between the bacterial load in the two groups, variation was observed in bacterial species. Most of the bacteria identified in distal oesophagus of the patients with gastroesophageal reflux were Gram negative., Significance and Impact of the Study: The human oesophagus was considered sterile until quite recently. Molecular techniques displayed the presence of a diverse bacterial species in the oesophagus. Although it is known that dysbiosis in the oesophagus causes GERD, and that Barrett's oesophagus can trigger the development of oesophageal adenocarcinoma, its etiopathogenesis is not clear. A limited number of published studies support the importance of the present study., (© 2019 The Society for Applied Microbiology.)

The authors report the case of the unexpected death of a fifty-year-old female found by her partner in the bathroom floor. External examination revealed some contusions dispersed by different corporal areas and an unusually placed green discoloration of the anterior cervical region. After neck dissection and opening the esophagus, a three and a half centimeter wooden toothpick fragment was found at the upper region, covered by a purulent substance associated with puncture wounds. Histopathological and microbiological studies revealed "acute bilateral cervical cellulitis" and Klebsiella Oxytoca, respectively. Further investigation revealed that during the five days prior to her death, the victim was observed twice in an emergency department with complains of throat discomfort after eating some bread with salami. X-Ray and a laryngoscopy were performed but did not reveal any significant findings. Due to the victim's medical history, she was evaluated by a psychiatrist that dismissed a non-somatic setting due to the type of complains and the elevation of blood inflammatory parameters. Rinopharyngitis was then assumed as the most likely diagnosis and was treated accordingly. The victim died the following day. This case reports an unusual fatal traumatic lesion to the upper esophagus that is a very important remainder, particularly for clinical practitioners, to maintain a high degree of suspicion, avoid diagnostic biases such as those related to psychiatric disorders and meticulously evaluate patients in order to deliver the most evidence-based diagnosis possible. To the best of the authors' knowledge there are no other cases described in the literature of a death caused by esophageal toothpick lesion., (Copyright © 2019 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Objective: Changes in microbiota composition in the distal esophagus may be associated with the pathogenesis of gastroesophageal reflux disease. We aimed to compare the composition of distal esophageal microbiota between Chinese patients with reflux esophagitis (RE) and healthy volunteers using metagenomic high-throughput DNA sequencing and bioinformatic analyses., Methods: Healthy volunteers (controls) and patients with reflux esophagitis (RE) were enrolled. Distal esophageal (2 cm above the gastroesophageal junction) biopsy specimens were obtained under endoscopy. Microbial DNA was extracted from the specimens, followed by 16S rDNA gene amplification and Illumina sequencing. Bioinformatic tools were applied to dissect the community structure., Results: No dramatic differences in microbiota were found in RE patients compared with the controls. At the phylum level, only Bacteroidetes differed between the groups, being less abundant in the RE group. The overall number and diversity of species tended to be lower in RE patients, but there were no significant differences between the groups. Three genera, Prevotella, Helicobacter, and Moraxella, were obviously depleted in RE patients, as revealed by linear discriminant analysis., Conclusions: The composition of distal esophageal microbiota in Chinese patients with RE showed moderate changes compared with healthy controls. To what extent these changes are associated with the pathogenesis of RE needs further investigation., (© 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Microbes within the gastrointestinal tract communicate with each other and with the host, which has profound effects on health and disease development. Only now, it is becoming apparent that how and when we acquire our own unique collection of "gut microbes" and also how we choose to maintain them is fundamental to our health. Helicobacter pylori is the most common bacterial infection worldwide, colonizing around half of the world's population, and is the major risk factor for gastric adenocarcinoma. More recently, it has also been shown to have some beneficial effects in terms of protecting against the development of other diseases. Here, we review the current knowledge on how H. pylori has shaped gastrointestinal microbiota colonization and the host immune system with specific focus on the impact of H. pylori on the various microbiome niches of the gastrointestinal tract. We discuss how the presence of H. pylori influences the physiology of three major regions within the gastrointestinal tract-specifically the oesophagus, stomach and colon. We pay particular attention to the role of H. pylori under chronic inflammatory conditions including the development of cancer. With increased incidence of diseases such as eosinophilic oesophagitis, oesophageal adenocarcinoma and squamous cell carcinoma being attributed to the decline in H. pylori, their disease pathogenesis in light of changing H. pylori colonization is also discussed.

Actinomycosis is a rare, chronic and slowly progressive granulomatous disease caused by Actinomyces spp., a Gram-positive anaerobic bacterium that rarely affects the esophagus. Although this infection is uncommon, it has been reported in both immunocompromised and immunocompetent individuals. The infection is often misdiagnosed because it can mimic other pathological conditions (like neoplasms and candidiasis), and Actinomyces is difficult to isolate because it requires specific growth conditions. However, actinomycosis has a favorable course if the microbiological diagnosis is timely. We report a case of esophageal actinomycosis in an immunocompetent 23-year-old man. The patient was admitted with symptoms of gastro-esophageal reflux disease (GERD), that had subsequently worsened. Histological and microbiological investigations revealed the presence of Actinomyces spp. A review of the literature regarding the clinical features, diagnosis, and management of this infection is also discussed.

Background: The esophageal microbiome has been proposed to be involved in a range of diseases including the esophageal adenocarcinoma cascade; however, little is currently known about its function and relationship to the host. Here, the esophageal microbiomes of 106 prospectively recruited patients were assessed using 16S rRNA and 18S rRNA amplicon sequencing as well as shotgun sequencing, and associations with age, gender, proton pump inhibitor use, host genetics, and disease were tested., Results: The esophageal microbiome was found to cluster into functionally distinct community types (esotypes) defined by the relative abundances of Streptococcus and Prevotella. While age was found to be a significant factor driving microbiome composition, bacterial signatures and functions such as enrichment with Gram-negative oral-associated bacteria and microbial lactic acid production were associated with the early stages of the esophageal adenocarcinoma cascade. Non-bacterial microbes such as archaea, Candida spp., and bacteriophages were also identified in low abundance in the esophageal microbiome. Specific host SNPs in NOTCH2, STEAP2-AS1, and NREP were associated with the composition of the esophageal microbiome in our cohort., Conclusions: This study provides the most comprehensive assessment of the esophageal microbiome to date and identifies novel signatures and host markers that can be investigated further in the context of esophageal adenocarcinoma development.

Risk factors for esophageal cancer include genetic factors (such as tylosis) and infectious agents. A variety of organisms have been implicated in esophageal carcinogenesis, either directly or indirectly. In this review, we explore the normal esophageal flora and how it may be controlled, and also the variety of organisms that may affect esophageal carcinogenesis, either directly or indirectly. The organisms with potential direct effects in squamous cell carcinoma include human papillomavirus (HPV), Epstein-Barr virus, and polyoma viruses. Interestingly, HPV is now implicated in esophageal adenocarcinoma (EAC), not in its initiation but in the development of dysplasia, in which HPV33 in particular has been associated. Indirectly, Helicobacter pylori has been associated with EAC by, initially, causing increased acid secretion that increases acid reflux, and by reducing lower esophageal sphincter pressure, which increases gastroesophageal reflux; the latter increases the risk of Barrett's esophagus, and hence EAC. Conversely, subsequent atrophic gastritis may normalize that risk., (© 2018 New York Academy of Sciences.)

Gastroenterologists frequently perform endoscopic esophageal mucosal biopsies for pathologic diagnosis in patients experiencing symptoms of esophagitis. The more common causes of esophagitis diagnosed on esophageal mucosal biopsy include reflux esophagitis, eosinophilic esophagitis, and infectious esophagitis caused by Candida albicans, herpes simplex virus, and/or cytomegalovirus. However, there are several causes of esophagitis seen less frequently by pathologists that are very important to recognize. We discuss unique types of esophageal inflammation, including acute bacterial esophagitis, esophageal manifestations of dermatologic diseases, medication-induced esophageal injury, and sloughing esophagitis; and we review their clinical and histopathologic features., (© 2018 New York Academy of Sciences.)

Infectious esophagitis is a leading cause of esophagitis worldwide. While esophageal infections have traditionally been associated with immunocompromised patients, these disorders are becoming increasingly recognized in immunocompetent individuals. The three most common etiologies of infectious esophagitis are Candida, herpes simplex virus, and cytomegalovirus. Human papilloma virus infection can also involve the esophagus in the form of ulcerative lesions and papillomas. Less common etiologies include various other fungal, bacterial, and viral organisms. This review provides a comprehensive update on risk factors, diagnosis, and management of both common and less common infections of the esophagus.

Background: Barrett’s oesophagus (BO) is a pre-malignant condition in which normal squamous epithelium of the lower oesophagus and gastresophageal junction is replaced by columnar cells and progress to oesophageal adenocarcinoma. The increase burden of oesophagus cancer morbidity and mortality worldwide make study of factors involved in the pathogenesis of BO essential. However, most of studies that examine the environmental risk factors associated with increased incidence and prevalence of BO have largely ignored the potential role of bacteria in disease aetiology. Aims: This study examined the role of Campylobacter concisus isolated from Barrett’s and adenocarcinoma patient samples as one of possible environmental factors in the progression of Barrett’s oesophagus to oesophagus adenocarcinoma. Methods: We focused on the effect of C. concisus on the expression caudal type homeobox 1 gene (CDX1) and cyclooxygenase-2 (COX-2) in three BO cell lines using quantitative real-time PCR. In addition, the attachment and invasion characteristics of C. concisus were also tested. Results: Results showed that C. concisus had a strong attachment to the cell lines and induce the expression of CDX1 in Barrett’s cell lines in a time-dependent manner. Conclusion: Findings indicate that C. concisus could be as a new challenge in the progression of BO to adenocarcinoma., (Creative Commons Attribution License)

Introduction: There is increasing evidence that the microbiome contributes to esophageal disease. Diet, especially fiber and fat intake, is a known potent modifier of the colonic microbiome, but its impact on the esophageal microbiome is not well described. We hypothesized that dietary fiber and fat intake would be associated with a distinct esophageal microbiome., Methods: We collected esophageal samples from 47 ambulatory patients scheduled to undergo endoscopy who completed a validated food frequency questionnaire quantifying dietary fiber and fat intake. Using 16S high-throughput sequencing, we determined composition of the esophageal microbiome and predicted functional capacity of microbiota based on fiber and fat intake., Results: Among all samples, the most abundant phyla were Firmicutes (54.0%), Proteobacteria (19.0%), Bacteroidetes (17.0%), Actinobacteria (5.2%), and Fusobacteria (4.3%). Increasing fiber intake was significantly associated with increasing relative abundance of Firmicutes (p = 0.04) and decreasing relative abundance of Gram-negative bacteria overall (p = 0.03). Low fiber intake was associated with increased relative abundance of several Gram-negative bacteria, including Prevotella, Neisseria, and Eikenella. Several predicted metabolic pathways differed between highest and lowest quartile of fiber intake. Fat intake was associated with altered relative abundance of few taxa, with no alterations at the phylum level and no changes in microbiome functional composition., Conclusions: Dietary fiber, but not fat, intake was associated with a distinct esophageal microbiome. Diet should be considered an important modifier of the esophageal microbiome in future studies. Studies are also needed to elucidate how the effects of dietary fiber on the esophageal microbiome may contribute to esophageal disease.

The rapa whelk Rapana venosa is a commercially important gastropod in China, but a major invader worldwide. There is little information on the bacterial community composition in the digestive system of this species, despite the microflora has important roles in digestion, nutrition, disease resistance, and immune response. The present study investigated the bacterial flora community in the esophagus and intestinal tract of wild R. venosa by 16S rRNA gene sequencing. The esophagus and intestine had 1175 and 526 unique operational taxonomic units, respectively, with 616 common to both tissues. The 10 most highly represented microbial genera in the esophagus were Mycoplasma, Bifidobacterium, Escherichia, Shewanella, Vibrio, Lactobacillus, Octadecabacter, Enterococcus, Streptococcus, and Sphingomonas, which accounted for 41.35% of microbes. In the intestine, the most abundant genera were Mycoplasma, Bifidobacterium, Escherichia, Shewanella, Vibrio, Psychrilyobacter, Peptoniphilus, Sporobacterium, Octadecabacter, and Mobiluncusin (representing 62.74% of total microbes). A linear discriminant analysis, coupled with effect size, revealed that 31 taxa were differentially represented in esophagus and intestine bacterial communities. These results demonstrate the diversity of microbiota in the esophagus and intestinal tract of R. venosa and provide a basis for investigations into the physiological and immunological roles of these microorganisms in whelk.

Purpose of Review: Investigation of the esophageal microbiome is a relatively new field. This review will outline data characterizing the esophageal microbiome in both health and disease states, including gastroesophageal reflux disease (GERD), Barrett's esophagus, esophageal cancer, eosinophilic esophagitis, and motility disorders., Recent Findings: While the esophagus was previously considered devoid of a significant bacterial population, development of culture-independent techniques, specifically 16S rRNA gene sequencing, as well as novel, minimally invasive microbial sampling modalities, has facilitated characterization of the esophageal microbiome in both health and several disease states. Although limited, there is evidence that the esophagus contains a diverse microbial population, with Gram-positive bacteria, specifically Streptococcus, dominating in health, while Gram-negative bacteria prevail in reflux disorders including GERD and Barrett's esophagus. The microbiome is altered with other esophageal disorders as well, including eosinophilic esophagitis and esophageal motility disorders, though these changes have been less well characterized. Characterization of the gut microbiome has advanced significantly; however, further investigation is essential. Understanding changes in the esophageal microbiome could affect our understanding of the natural history of diseases of the esophagus and present potential therapeutic approaches.

BACKGROUND The effects of Helicobacter pylori (H. pylori) infection on gastroesophageal reflux disease (GERD) remain unclear. The aim of this study was to compare the results of clinical esophageal function tests and the effect of H. pylori infection on GERD. MATERIAL AND METHODS A prospective clinical study included 124 patients diagnosed with GERD (four grades). H. pylori infection was determined by gastroscopy and a rapid urease test (RUT) to divide patients into an HP-positive and an HP-negative group. Esophageal function tests included high-resolution manometry (HRM), peristalsis break (PB), and 24-hour pH monitoring (composite pH DeMeester score). Different grades of GERD, with and without H. pylori infection, esophageal function test results were analyzed. RESULTS The HP-positive group, compared with the HP-negative group with GERD, showed a significantly reduced median PB value (3.41±3.65 vs. 6.18±5.27), reduced PBs >5 cm per ten swallows (2.23±3.05 vs. 4.04±3.70) indicating that that H. pylori infection improved esophageal peristalsis. During 24-hour esophageal pH monitoring, the HP-positive group showed a significantly reduced percentage of time for esophageal pH <4.0, number of reflux events >5 min, and number of reflux episodes in 24 hours, compared with the HP-negative group. The DeMeester score was significantly increased in the HP-negative group, indicating a higher esophageal acid exposure (9.11±8.15 vs. 24.30±30.27). CONCLUSIONS H. pylori infection improved esophageal peristalsis, enhanced lower esophageal sphincter (LES) pressure, and reduced esophageal acid exposure, which might be protective factors for GERD.

Background: The healthy human esophagus is colonized by bacteria similar to that of the oral mucosa. However, little is known about the microbiome of the esophagus in esophagitis or the possible role of bacteria in the inflammatory response., Aim: To survey bacterial diversity and compare the microbiome of the esophagus in subjects with gastro-esophageal reflux disease (GERD) and eosinophilic esophagitis (EoE)., Material and Methods: Seventeen subjects diagnosed with GERD and 10 with EoE underwent endoscopic examination with brush sampling and biopsies from the oral cavity, upper and lower esophagus. The samples were cultivated on agar plates, and bacterial growth was identified to the genus or species level and semi-quantified., Results: Significantly higher numbers of bacterial groups or species were found in specimens from the lower esophagus in subjects with EoE compared to subjects with GERD (median 4 (range 1-7) vs. 2 (range 0-6), p < .0014). Sixteen vs. 14 different bacterial groups or species were found in subjects with GERD and EoE, respectively, mostly in sparse or very sparse amounts. Alfa-streptococci (viridans streptococci) were the most common bacteria in both groups. Streptococci were present in all of the EoE-subjects but only in approximately 75% in lower esophagus of the GERD-subjects, regardless of the sampling method., Conclusion: Subjects with GERD had significantly less bacterial diversity in both oral and esophageal samples than EoE-subjects. Whether this discrepancy might be explained by an effect on the protective mucosal biofilm by the acidic content of the reflux in subjects with GERD remains unclear.

Dysregulation of microRNAs (miRNAs) has been linked to virulence factors of Helicobacter pylori. The role of H. pylori in esophageal disease has not been clearly defined. We previously reported that H. pylori esophageal colonization promotes the incidence of Barrett's esophagus and esophageal adenocarcinoma in vivo. Here, we studied the direct effects of H. pylori on the transformation of esophageal epithelial cells, with particular focus on whether H. pylori exerts its effects by modulating miRNAs and their downstream target genes. The normal human esophageal cell line HET-1A was chronically exposed to H. pylori extract and/or acidified deoxycholic acid for up to 36 weeks. The miRNA profiles of the esophageal epithelial cells associated with H. pylori infection were determined by microarray analysis. We found that chronic H. pylori exposure promoted acidified deoxycholic acid-induced morphological changes in HET-1A cells, along with aberrant overexpression of intestinal metaplasia markers and tumorigenic factors, including caudal-type homeobox protein 2 (CDX2), mucin 2, and cyclooxygenase 2 (COX2). Helicobacter pylori modified the miRNA profiles of esophageal epithelial cells, particularly aberrant silencing of miR-212-3p and miR-361-3p. Moreover, in biopsies from Barrett's esophagus patients, esophageal H. pylori colonization was associated with a significant decrease in miR-212-3p and miR-361-3p expression. Furthermore, we identified COX2 as a target of miR-212-3p, and CDX2 as a target of miR-361-3p. Helicobacter pylori infection of esophageal epithelial cells was associated with miRNA-mediated upregulation of oncoprotein CDX2 and COX2. Our observations provide new evidence about the molecular mechanisms underlying the association between H. pylori infection and esophageal carcinogenesis., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Introduction: Acute esophageal necrosis, also known as black esophagus, is a rare digestive complication, frequently manifested by an upper gastrointestinal hemorrhage and occurs in patients with comorbidities., Aim: To report the case of a patient with a black esophagus revealed by an upper gastrointestinal hemorrhage., Observation: A 72-year-old patient with a history of diabetes mellitus, hypertension and ischemic heart disease was hospitalized in surgical intensive care unit for hemorrhagic shock induced by cholecystectomy. On the 7th postoperative day, the patient developed acute hematemesis. Gastroscopy showed circumferential necrosis, localized in the middle and lower third of the esophagus and stopped abruptly at the gastroesophageal junction. Gastric mucosa was strictly normal. The bulb and the first part of duodenum showed multiple superficial ulcers without signs of recent hemorrhage. The patient was placed on absolute diet and total parenteral nutrition associated with high-dose intravenous proton pump inhibitor. Second-look gastroscopy, performed six days later, showed a significant improvement in esophageal lesions. The evolution was marked by the occurrence of pneumonia complicated by septic shock which caused patient's death., Conclusion: Black esophagus is a rare pathology of multifactorial etiology. Treatment is based on proton pump inhibitors in combination with resuscitation measures to control comorbidities. Mortality remains high due to the seriousness of comorbid disease states often associated with this condition.

Here, we present a case of a 50-year-old male with a history of a Guillain-Barré-syndrome, who was referred to our clinic with recurrent esophageal candidiasis and long-standing intermittent retrosternal cramps for further evaluation. Other symptoms such as dysphagia, regurgitations and weight loss were denied, and prior repeated endoscopy was otherwise unremarkable. Using high resolution impedance manometry, we could demonstrate a panesophageal pressure increase on water swallows and complete aperistalsis of the tubular esophagus, indicating achalasia type II. However, due to the patient's extraordinary body height and resulting length of the esophagus, endoluminal functional lumen imaging probe analysis supplementary to high resolution impedance manometry needed to be used to assess distensibility of the esophagogastral junction and to secure the diagnosis of achalasia before appropriately treating the patient with pneumatic dilation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)