RESUMO
We examined Fusobacterium nucreatum (F. nucleatum) and whole Fusobacterium species (Pan-fusobacterium) in non-neoplastic Barrett's esophagus (BE) from patients without cancer (n = 67; N group), with esophageal adenocarcinoma (EAC) (n = 27) and EAC tissue (n = 22). F. nucleatum was only detectable in 22.7% of EAC tissue. Pan-fusobacterium was enriched in EAC tissue and associated with aggressive clinicopathological features. Amount of Pan-fusobacterium in non-neoplastic BE was correlated with presence of hital hernia and telomere shortening. The result suggested potential association of Fusobacterium species in EAC and BE, featuring clinicpathological and molecular features.
Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/microbiologia , Neoplasias Esofágicas/patologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Esôfago de Barrett/microbiologia , Esôfago de Barrett/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Fusobacterium/isolamento & purificação , Fusobacterium/genética , Fusobacterium nucleatum/isolamento & purificação , AdultoRESUMO
Esophageal adenocarcinoma (EAC) is one of the most malignant tumors in the digestive system. To make thing worse, the scarcity of treatment options is disheartening. However, if detected early, there is a possibility of reversing the condition. Unfortunately, there is still a lack of relevant early screening methods. Considering that Barrett's esophagus (BE), a precursor lesion of EAC, has been confirmed as the only known precursor of EAC. Analyzing which BE cases will progress to EAC and understanding the processes and mechanisms involved is of great significance for early screening of such patients. Considering the significant alterations in the gut microbiota of patients with BE and its potential role in the progression to EAC, this study aims to analyze the relationship between BE, EAC, and GM to identify potential diagnostic biomarkers and therapeutic targets. This study utilized comprehensive statistical data on gut microbiota from a large-scale genome-wide association meta-analysis conducted by the MiBioGen consortium (n = 18,340). Subsequently, we selected a set of single nucleotide polymorphisms (SNPs) that fell below the genome-wide significance threshold (1 × 10-5) as instrumental variables. To investigate the causal relationship between gut microbiota and BE and EAC, we employed various MR analysis methods, including Inverse Variance Weighting (IVW), MR-Egger regression, weighted median (WM), and weighted mean. Additionally, we assessed the level of pleiotropy, heterogeneity, and stability of genetic variations through MR-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis. Furthermore, we conducted reverse MR analysis to identify the causal relationships between gut microbiota and BE and EAC. The results from the Inverse Variance-Weighted (IVW) analysis indicate that Alistipes (P = 4.86 × 10-2), Lactobacillus (P = 2.11 × 10-2), Prevotella 7 (P = 4.28 × 10-2), and RuminococcaceaeUCG004 (P = 4.34 × 10-2) are risk factors for Barrett's esophagus (BE), while Flavonifractor (P = 8.81 × 10-3) and RuminococcaceaeUCG004 (P = 4.99 × 10-2) are risk factors for esophageal adenocarcinoma (EAC). On the other hand, certain gut microbiota genera appear to have a protective effect against both BE and EAC. These include Eubacterium (nodatum group) (P = 4.51 × 10-2), Holdemania (P = 1.22 × 10-2), and Lactococcus (P = 3.39 × 10-2) in the BE cohort, as well as Eubacterium (hallii group) (P = 4.07 × 10-2) and Actinomyces (P = 3.62 × 10-3) in the EAC cohort. According to the results of reverse MR analysis, no significant causal effects of BE and EAC on gut microbiota were observed. Furthermore, no significant heterogeneity or pleiotropy was detected in the instrumental variables. We have established a causal relationship between the gut microbiota and BE and EAC. This study holds profound significance for screening BE patients who may be at risk of deterioration, as it can provide them with timely medical interventions to reverse the condition.
Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Esôfago de Barrett/genética , Esôfago de Barrett/microbiologia , Esôfago de Barrett/patologia , Microbioma Gastrointestinal/genética , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/microbiologia , Neoplasias Esofágicas/patologia , Adenocarcinoma/genética , Adenocarcinoma/microbiologia , Adenocarcinoma/patologiaRESUMO
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.
Assuntos
Esôfago de Barrett , Refluxo Gastroesofágico , Microbioma Gastrointestinal , Análise da Randomização Mendeliana , Microbioma Gastrointestinal/genética , Refluxo Gastroesofágico/microbiologia , Humanos , Esôfago de Barrett/microbiologia , Esôfago de Barrett/genética , Fatores de Risco , Polimorfismo de Nucleotídeo ÚnicoRESUMO
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.
Assuntos
Esôfago de Barrett , Infecções por Helicobacter , Helicobacter pylori , Humanos , Esôfago de Barrett/microbiologia , Esôfago de Barrett/patologia , Esôfago de Barrett/complicações , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Masculino , Estudos Retrospectivos , Feminino , Helicobacter pylori/isolamento & purificação , Idoso , Pessoa de Meia-Idade , Esofagite Péptica/etiologia , Esofagite Péptica/epidemiologia , Esofagite Péptica/microbiologia , Antibacterianos/uso terapêutico , Esôfago/microbiologia , Esôfago/patologia , Esôfago/diagnóstico por imagem , Hérnia Hiatal/complicações , Refluxo Gastroesofágico/microbiologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/epidemiologia , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Risco , SeguimentosRESUMO
Accurate and rapid point-of-care tissue and microbiome sampling is critical for early detection of cancers and infectious diseases and often result in effective early intervention and prevention of disease spread. In particular, the low prevalence of Barrett's and gastric premalignancy in the Western world makes population-based endoscopic screening unfeasible and cost-ineffective. Herein, we report a method that may be useful for prescreening the general population in a minimally invasive way using a swallowable, re-expandable, ultra-absorbable, and retrievable nanofiber cuboid and sphere produced by electrospinning, gas-foaming, coating, and crosslinking. The water absorption capacity of the cuboid- and sphere-shaped nanofiber objects is shown â¼6000% and â¼2000% of their dry mass. In contrast, unexpanded semicircular and square nanofiber membranes showed <500% of their dry mass. Moreover, the swallowable sphere and cuboid were able to collect and release more bacteria, viruses, and cells/tissues from solutions as compared with unexpanded scaffolds. In addition to that, an expanded sphere shows higher cell collection capacity from the esophagus inner wall as compared with the unexpanded nanofiber membrane. Taken together, the nanofiber capsules developed in this study could provide a minimally invasive method of collecting biological samples from the duodenal, gastric, esophagus, and oropharyngeal sites, potentially leading to timely and accurate diagnosis of many diseases. STATEMENT OF SIGNIFICANCE: Recently, minimally invasive technologies have gained much attention in tissue engineering and disease diagnosis. In this study, we engineered a swallowable and retrievable electrospun nanofiber capsule serving as collection device to collect specimens from internal organs in a minimally invasive manner. The sample collection device could be an alternative endoscopy to collect the samples from internal organs like jejunum, stomach, esophagus, and oropharynx without any sedation. The newly engineered nanofiber capsule could be used to collect, bacteria, virus, fluids, and cells from the abovementioned internal organs. In addition, the biocompatible and biodegradable nanofiber capsule on a string could exhibit a great sample collection capacity for the primary screening of Barret Esophagus, acid reflux, SARS-COVID-19, Helicobacter pylori, and gastric cancer.
Assuntos
Esôfago de Barrett , COVID-19 , Nanofibras , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/microbiologia , Esôfago de Barrett/patologia , Cápsulas , HumanosRESUMO
INTRODUCTION: Alterations in the composition of the human gut microbiome and its metabolites have been linked to gut epithelial neoplasia. We hypothesized that differences in mucosa-adherent Barrett's microbiota could link to risk factors, providing risk of progression to neoplasia. METHODS: Paired biopsies from both diseased and nonaffected esophagus (as well as gastric cardia and gastric juice for comparison) from patients with intestinal metaplasia (n = 10), low grade dysplasia (n = 10), high grade dysplasia (n = 10), esophageal adenocarcinoma (n = 12), and controls (n = 10) were processed for mucosa-associated bacteria and analyzed by 16S ribosomal ribonucleic acid V4 gene DNA sequencing. Taxa composition was tested using a generalized linear model based on the negative binomial distribution and the log link functions of the R Bioconductor package edgeR. RESULTS: The microbe composition of paired samples (disease vs nondisease) comparing normal esophagus with intestinal metaplasia, low grade dysplasia, high grade dysplasia, and adenocarcinoma showed significant decreases in the phylum Planctomycetes and the archaean phylum Crenarchaeota (P < 0.05, false discovery rate corrected) in diseased tissue compared with healthy controls and intrasample controls (gastric juice and unaffected mucosa). Genera Siphonobacter, Balneola, Nitrosopumilus, and Planctomyces were significantly decreased (P < 0.05, false discovery rate corrected), representing <10% of the entire genus community. These changes were unaffected by age, tobacco use, or sex for Crenarcha. DISCUSSSION: There are similar significant changes in bacterial genera in Barrett's esophageal mucosa, dysplasia, and adenocarcinoma compared with controls and intrapatient unaffected esophagus. Further work will establish the biologic plausibility of these specific microbes' contributions to protection from or induction of esophageal epithelial dysplasia.
Assuntos
Adenocarcinoma/microbiologia , Esôfago de Barrett/microbiologia , Mucosa Esofágica/microbiologia , Neoplasias Esofágicas/microbiologia , Microbioma Gastrointestinal , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/patologia , Biópsia , Estudos de Casos e Controles , DNA Bacteriano/isolamento & purificação , Progressão da Doença , Mucosa Esofágica/diagnóstico por imagem , Mucosa Esofágica/patologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Esofagoscopia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , RNA Ribossômico 16S/genética , Fatores de RiscoRESUMO
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 ß-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.
Assuntos
Adenocarcinoma/microbiologia , Bactérias/classificação , Esôfago de Barrett/microbiologia , Neoplasias Esofágicas/microbiologia , Esôfago/microbiologia , Análise de Sequência de DNA/métodos , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Casos e Controles , DNA Bacteriano/genética , DNA Ribossômico/genética , Feminino , Humanos , Masculino , Microbiota , Pessoa de Meia-Idade , Filogenia , Projetos Piloto , RNA Ribossômico 16S/genéticaRESUMO
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.
Assuntos
Mucosa Esofágica/microbiologia , Microbioma Gastrointestinal/fisiologia , Interações entre Hospedeiro e Microrganismos/genética , Adulto , Idoso , Esôfago de Barrett/microbiologia , Esôfago de Barrett/patologia , Biópsia , Clorexidina/administração & dosagem , DNA Bacteriano/isolamento & purificação , Esofagite Eosinofílica/microbiologia , Esofagite Eosinofílica/patologia , Mucosa Esofágica/diagnóstico por imagem , Mucosa Esofágica/patologia , Esofagoscopia , Feminino , Seguimentos , Refluxo Gastroesofágico/microbiologia , Refluxo Gastroesofágico/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/microbiologia , Antissépticos Bucais/administração & dosagem , RNA Ribossômico 16S/genética , RNA-Seq , Saliva/microbiologiaRESUMO
BACKGROUND AND AIM: The etiology and pathogenesis of Barrett's esophagus (BE) have been widely studied during recent decades. However, the association between BE and possible risk factors, including abdominal obesity (AO), metabolic syndrome (MetS), insulin resistance (IR), and the microbiome has not reached a consensus and lacks a systematic assessment. The purpose of our study is to evaluate, quantify, and summarize the association between these factors and BE risk. METHODS: A systematic search of Pubmed, Embase, and Cochrane Library databases was performed to identify relevant studies before September 2018. Studies were estimated with the OR, the weighted mean difference (WMD), and the 95% CI by using a random effects model. Subgroup analysis and publication bias were also performed. RESULTS: A total of 46 citations were included in the analysis, and 119,273 subjects were analyzed (AO 13, MetS 15, IR 9, and microbiome: 9). The pooled results showed that AO (p < 0.01, OR 1.30, 95% CI 1.11-1.52, I2 = 31.9%), MetS (p < 0.01, OR 1.68, 95% CI 1.40-2.01, I2 = 87.6%), and IR (p < 0.01, WMD 0.23, 95% CI 0.11-0.35, I2 = 55.8%) were all significantly associated with an increased risk of BE, but except for the microbiome (p > 0.05, OR 1.27, 95% CI 0.66-2.43, I2 = 46.7%). In addition, subgroup analyses were stratified by waist-to-hip ratio, waist circumference, body mass index, diagnosis criteria, strain type, geographical region, and study design, respectively. Moreover, we observed no evidence of publication bias in Egger's and Begg's tests. CONCLUSIONS: Our study reveals that AO, MetS, and IR are significantly associated with BE risk, except for the microbiome. The mechanism of BE induced by 3 risk factors should be further explored.
Assuntos
Esôfago de Barrett/diagnóstico , Esôfago de Barrett/microbiologia , Resistência à Insulina , Síndrome Metabólica/complicações , Microbiota , Obesidade/complicações , Adulto , Esôfago de Barrett/complicações , Índice de Massa Corporal , Feminino , Humanos , Fatores de RiscoRESUMO
BACKGROUND: The presence of intestinal metaplasia in the distal esophagus (Barrett's esophagus) is an important precursor of adenocarcinoma. Knowledge of the risk factors and the process by which the Barrett develops is very important and Helicobacter pylori (HP) can contribute to this development. AIM: To analyze the impact of HP in the gastric mucosa with intestinal metaplasia in the distal esophagus in areas of columnar epithelialization smaller than 10 mm in length and epidemiological data on prevalence. METHOD: A retrospective study in which were included 373 consecutive patients diagnosed with columnar epithelium in the distal esophagus was done. In all, HP was investigated by urease and histology, exclusion and inclusion factors were applied and patients were divided into two groups: the first grouping the ones without histological diagnosis of Barrett's esophagus (235-63%) and the second with it (138-37%). RESULTS: There was no significant difference between HP and non-HP patients in relation to the probability of having intestinal metaplasia (p=0.587). When related to the general group, there was an inverse association between the bacterium and the columnar epithelia in the distal esophagus. Age (p=0.031), gender (p=0.013) and HP (p=0.613) when related together to intestinal metaplasia showed no significant relation. In isolation, when related to age and gender, regardless of HP, results confirmed that patients in more advanced age and women present a higher incidence of intestinal metaplasia. CONCLUSION: There is an inverse relation between HP and the areas of columnar epithelization in the distal esophagus, regardless of the presence or absence of intestinal metaplasia. Age and gender, regardless of HP, showed higher prevalence in women and in older the number of cases with intestinal metaplasia in the distal esophagus.
Assuntos
Esôfago de Barrett/patologia , Epitélio/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Adulto , Fatores Etários , Idoso , Esôfago de Barrett/microbiologia , Epitélio/microbiologia , Feminino , Humanos , Masculino , Metaplasia/microbiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores SexuaisRESUMO
BACKGROUND: The incidence of esophageal adenocarcinoma has risen dramatically over the past half century, and the underlying reasons are incompletely understood. Broad shifts to the upper gastrointestinal microbiome may be partly responsible. The goal of this study was to describe alterations in the esophageal microbiome that occur with progression from Barrett's esophagus to esophageal adenocarcinoma. METHODS: A case-control study was performed of patients with and without Barrett's esophagus who were scheduled to undergo upper endoscopy. Demographic, clinical, and dietary intake data were collected, and esophageal brushings were collected during the endoscopy. 16S rRNA gene sequencing was performed to characterize the microbiome. RESULTS: A total of 45 patients were enrolled and included in the analyses [16 controls; 14 Barrett's esophagus without dysplasia (NDBE); 6 low-grade dysplasia (LGD); 5 high-grade dysplasia (HGD); and 4 esophageal adenocarcinoma]. There was no difference in alpha diversity between non-Barrett's esophagus and Barrett's esophagus, but there was evidence of decreased diversity in patients with esophageal adenocarcinoma as assessed by Simpson index. There was an apparent shift in composition at the transition from LGD to HGD, and patients with HGD and esophageal adenocarcinoma had decreased Firmicutes and increased Proteobacteria. In addition, patients with HGD or esophageal adenocarcinoma had increased Enterobacteriaceae and Akkermansia muciniphila and reduced Veillonella. In the study population, patients taking proton pump inhibitors had increased Streptococcus and decreased Gram-negative bacteria overall. CONCLUSIONS: Shifts in the Barrett's esophagus-associated microbiome were observed in patients with HGD and esophageal adenocarcinoma, with increases in certain potentially pathogenic bacteria. IMPACT: The microbiome may play a role in esophageal carcinogenesis.
Assuntos
Adenocarcinoma/microbiologia , Bactérias/classificação , Esôfago de Barrett/microbiologia , Neoplasias Esofágicas/microbiologia , Microbiota , Lesões Pré-Cancerosas/microbiologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Bactérias/genética , Bactérias/isolamento & purificação , Esôfago de Barrett/genética , Esôfago de Barrett/patologia , Progressão da Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , PrognósticoRESUMO
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.
Assuntos
Endoscópios/microbiologia , Esôfago/microbiologia , Orofaringe/microbiologia , Adulto , Esôfago de Barrett/microbiologia , Biópsia/métodos , Mucosa Esofágica/microbiologia , Feminino , Humanos , Masculino , Microbiota , Pessoa de Meia-Idade , Úvula/microbiologiaRESUMO
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.
Assuntos
Adenocarcinoma/microbiologia , Neoplasias Esofágicas/microbiologia , Infecções por Helicobacter/complicações , Adenocarcinoma/patologia , Esôfago de Barrett/microbiologia , Esôfago de Barrett/patologia , Mucosa Esofágica/patologia , Neoplasias Esofágicas/patologia , Refluxo Gastroesofágico/microbiologia , Refluxo Gastroesofágico/patologia , Infecções por Helicobacter/patologia , Humanos , Fatores de RiscoRESUMO
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.
Assuntos
Adenocarcinoma/diagnóstico , Esôfago de Barrett/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/diagnóstico , Esôfago/patologia , Lesões Pré-Cancerosas/diagnóstico , Adenocarcinoma/química , Adenocarcinoma/etiologia , Adenocarcinoma/microbiologia , Esôfago de Barrett/complicações , Esôfago de Barrett/genética , Esôfago de Barrett/microbiologia , Biomarcadores Tumorais/análise , Endoscopia por Cápsula , Neoplasias Esofágicas/química , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/microbiologia , Esofagoscopia , Esôfago/química , Esôfago/microbiologia , Humanos , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/microbiologiaRESUMO
The incidence of esophageal adenocarcinoma (EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus (BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux (GER), male sex, older age, central obesity, tobacco smoking, Helicobacter pylori (H. pylori) eradication, and the administration of proton pump inhibitors (PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes, Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type I microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type II microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.
Assuntos
Adenocarcinoma/microbiologia , Esôfago de Barrett/microbiologia , Disbiose/patologia , Mucosa Esofágica/microbiologia , Neoplasias Esofágicas/microbiologia , Microbioma Gastrointestinal/fisiologia , Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Disbiose/microbiologia , Mucosa Esofágica/patologia , Neoplasias Esofágicas/patologia , Humanos , Fatores de RiscoRESUMO
This study examines the effects of environmental hazards, including tobacco, alcohol/alcohol flush response, areca nut, and Helicobacter pylori (H pylori) infection on upper digestive diseases. This is a multi-hospital-based endoscopy-survey cross-sectional study. Subjects were received upper endoscopies in outpatient clinics at four hospitals in Taiwan between 2008 and 2013. Biopsy-based methods or urea breath test were used confirm the status of H pylori infection. In total, 8135 subjects were analyzed. Higher cumulative amounts of alcohol consumption were at higher risk of Barrett's esophagus and esophageal squamous cell carcinoma (ESCC), higher cumulative amounts of tobacco consumption were at higher risk of peptic ulcer, and higher cumulative amounts of areca nut consumption were at higher risk of duodenitis. Alcohol flush response was significant risk for reflux esophagitis and Barrett's esophagus (adjusted odds ratio [aOR] = 1.18 and 1.32, 95% confidence interval [CI] = 1.07-1.31 and 1.06-1.65, respectively). H pylori infection was inversely associated with ESCC risk (aOR = 0.20, 95% CI = 0.10-0.40). In addition, H pylori infection was consistently and significantly risk factors for gastrointestinal diseases, including peptic ulcer, gastric adenocarcinoma, and duodenitis (aOR = 5.51, 1.84, and 2.10, 95% CI = 4.85-6.26, 1.03-3.26, and 1.71-2.56, respectively). Besides the cumulative risk of alcohol, tobacco, and areca nut for Barrett's esophagus, ESCC, and peptic ulcer, respectively, presence of facial flushing was the significant risk for reflux esophagitis and Barrett's esophagus. H pylori infection was positively associated with peptic ulcer, gastric adenocarcinoma, and duodenitis, but inversely associated with ESCC.
Assuntos
Adenocarcinoma/diagnóstico , Esôfago de Barrett/diagnóstico , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Infecções por Helicobacter/diagnóstico , Úlcera Péptica/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/etiologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Areca/química , Esôfago de Barrett/etiologia , Esôfago de Barrett/microbiologia , Esôfago de Barrett/patologia , Estudos Transversais , Duodenite/diagnóstico , Duodenite/etiologia , Duodenite/microbiologia , Duodenite/patologia , Endoscopia do Sistema Digestório , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/microbiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/etiologia , Carcinoma de Células Escamosas do Esôfago/microbiologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Rubor/complicações , Rubor/fisiopatologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Infecções por Helicobacter/etiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Helicobacter pylori/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nozes/química , Úlcera Péptica/etiologia , Úlcera Péptica/microbiologia , Úlcera Péptica/patologia , Fatores de Risco , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Taiwan , Uso de Tabaco/efeitos adversosRESUMO
ABSTRAT Background: The presence of intestinal metaplasia in the distal esophagus (Barrett's esophagus) is an important precursor of adenocarcinoma. Knowledge of the risk factors and the process by which the Barrett develops is very important and Helicobacter pylori (HP) can contribute to this development. Aim: To analyze the impact of HP in the gastric mucosa with intestinal metaplasia in the distal esophagus in areas of columnar epithelialization smaller than 10 mm in length and epidemiological data on prevalence Method: A retrospective study in which were included 373 consecutive patients diagnosed with columnar epithelium in the distal esophagus was done. In all, HP was investigated by urease and histology, exclusion and inclusion factors were applied and patients were divided into two groups: the first grouping the ones without histological diagnosis of Barrett's esophagus (235-63%) and the second with it (138-37%). Results: There was no significant difference between HP and non-HP patients in relation to the probability of having intestinal metaplasia (p=0.587). When related to the general group, there was an inverse association between the bacterium and the columnar epithelia in the distal esophagus. Age (p=0.031), gender (p=0.013) and HP (p=0.613) when related together to intestinal metaplasia showed no significant relation. In isolation, when related to age and gender, regardless of HP, results confirmed that patients in more advanced age and women present a higher incidence of intestinal metaplasia. Conclusion: There is an inverse relation between HP and the areas of columnar epithelization in the distal esophagus, regardless of the presence or absence of intestinal metaplasia. Age and gender, regardless of HP, showed higher prevalence in women and in older the number of cases with intestinal metaplasia in the distal esophagus.
RESUMO Racional: A presença de metaplasia intestinal no esôfago distal (esôfago de Barrett) é importante doença precursora do adenocarcinoma. O conhecimento sobre os fatores de risco e o processo pelo qual ela se desenvolve é importante e o Helicobacter pylori (HP) pode contribuir para esse desenvolvimento. Objetivo: Analisar o impacto do HP na mucosa gástrica sobre a metaplasia intestinal no esôfago distal em áreas de epitelização colunar menores que 10 mm de extensão e dados epidemiológicos de prevalência. Método: Estudo retrospectivo com inclusão de 373 pacientes consecutivos, com diagnóstico de epitélio colunar no esôfago distal. Em todos foi pesquisado o HP pela urease e histologia, aplicados os fatores de exclusão e inclusão e divididos em dois grupos: o primeiro agregando os pacientes sem diagnóstico histológico de esôfago de Barrett (235-63%) e o segundo com ele (138-37%). Resultados: Não houve diferença significativa entre os portadores ou não do HP em relação à probabilidade de ter metaplasia intestinal (p=0,587). Quando relacionado ao grupo geral, houve associação inversa entre a bactéria e a epitelização colunar em esôfago distal. A idade (p=0,031), gênero (p=0,013) e HP (p=0,613) quando relacionados juntos à metaplasia intestinal não mostraram relação significativa. Isoladamente, quando relacionados idade e gênero, independente do HP, surgiram resultados confirmando que pacientes de idade mais avançada e mulheres apresentam maior incidência de metaplasia intestinal. Conclusão: Existe relação inversa entre HP e as áreas de epitelização colunar em esôfago distal, independente da presença ou não de metaplasia intestinal. Já em relação à idade e gênero, independente do HP, notou-se que em mulheres e com maior a idade há aumento no número de casos com metaplasia intestinal no esôfago distal.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Esôfago de Barrett/patologia , Helicobacter pylori , Infecções por Helicobacter/patologia , Epitélio/patologia , Esôfago de Barrett/microbiologia , Fatores Sexuais , Estudos Retrospectivos , Fatores Etários , Epitélio/microbiologia , Metaplasia/microbiologia , Metaplasia/patologiaRESUMO
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.
Assuntos
Doenças do Esôfago/microbiologia , Esôfago/microbiologia , Microbiota , Esôfago de Barrett/microbiologia , Disbiose/microbiologia , Esofagite Eosinofílica/microbiologia , Neoplasias Esofágicas/microbiologia , Refluxo Gastroesofágico/microbiologia , HumanosRESUMO
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.