Microbiome of esophageal endoscopic wash samples is associated with resident flora in the esophagus and incidence of cancer
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SUBMITTER: Shijimaya T
PROVIDER: S-EPMC11341785 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Background & aimsAlthough patients with Barrett's esophagus commonly undergo endoscopic surveillance, its effectiveness in reducing mortality from esophageal/gastroesophageal junction adenocarcinomas has not been evaluated rigorously.MethodsWe performed a case-control study in a community-based setting. Among 8272 members with Barrett's esophagus, we identified 351 esophageal adenocarcinoma: 70 in persons who had a prior diagnosis of Barrett's esophagus (who were eligible for surveillance); 51 of these patients died, 38 as a result of the cancers (cases). Surveillance histories were contrasted with a sample of 101 living persons with Barrett's esophagus (controls), matched for age, sex, and duration of follow-up evaluation.ResultsSurveillance within 3 years was not associated with a decreased risk of death from esophageal adenocarcinoma (adjusted odds ratio, 0.99; 95% confidence interval, 0.36-2.75). Fatal cases were nearly as likely to have received surveillance (55.3%) as were controls (60.4%). A Barrett's esophagus length longer than 3 cm and prior dysplasia each were associated with subsequent mortality, but adjustment for these did not change the main findings. Although all patients should be included in evaluations of effectiveness, excluding deaths related to cancer treatment and patients who failed to complete treatment, changed the magnitude, but not the significance, of the association (odds ratio, 0.46; 95% confidence interval, 0.13-1.64).ConclusionsEndoscopic surveillance of patients with Barrett's esophagus was not associated with a substantially decreased risk of death from esophageal adenocarcinoma. The results do not exclude a small to moderate benefit. However, if such a benefit exists, our findings indicate that it is substantially smaller than currently estimated. The effectiveness of surveillance was influenced partially by the acceptability of existing treatments and the occurrence of treatment-associated mortality.
| S-EPMC3767470 | biostudies-literature
Project description:BackgroundThe 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.MethodsA 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.ResultsA 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.ConclusionsShifts in the Barrett's esophagus-associated microbiome were observed in patients with HGD and esophageal adenocarcinoma, with increases in certain potentially pathogenic bacteria.ImpactThe microbiome may play a role in esophageal carcinogenesis.
| S-EPMC6774849 | biostudies-literature
Project description: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.
| S-EPMC7199943 | biostudies-literature
Project description: Not available
| S-EPMC6301555 | biostudies-literature
Project description:Esophageal adenocarcinoma (EAC) is rising in incidence and associated with poor survival, and established risk factors do not explain this trend. Microbiome alterations have been associated with progression from the precursor Barrett's esophagus (BE) to EAC, yet the oral microbiome, tightly linked to the esophageal microbiome and easier to sample, has not been extensively studied in this context. We aimed to assess the relationship between the salivary microbiome and neoplastic progression in BE to identify microbiome-related factors that may drive EAC development. We collected clinical data and oral health and hygiene history and characterized the salivary microbiome from 250 patients with and without BE, including 78 with advanced neoplasia (high grade dysplasia or early adenocarcinoma). We assessed differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features and used microbiome metabolic modeling to predict metabolite production. We found significant shifts and increased dysbiosis associated with progression to advanced neoplasia, with these associations occurring independent of tooth loss, and the largest shifts were with the genus Streptococcus. Microbiome metabolic models predicted significant shifts in the metabolic capacities of the salivary microbiome in patients with advanced neoplasia, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production. Our results suggest both a mechanistic and predictive role for the oral microbiome in esophageal adenocarcinoma. Further work is warranted to identify the biological significance of these alterations, to validate metabolic shifts, and to determine whether they represent viable therapeutic targets for prevention of progression in BE.
| S-EPMC10327009 | biostudies-literature
Project description:Background and aimThe study aims to clarify the endoscopic features and clinicopathological differences in superficial Barret's esophageal adenocarcinoma (s-BEA) derived from short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE).MethodsWe reviewed data of 130 patients (141 lesions) with pathologically confirmed s-BEA (SSBE: 95 patients and 95 lesions; LSBE: 35 patients and 46 lesions). We analyzed endoscopic and clinicopathological features of s-BEA in patients with SSBE and LSBE.ResultsThe distribution of lesions according to macroscopic findings were as follows (s-BEA in SSBE vs LSBE): flat type (0-IIb), 3.2% (3/95) vs 32.6% (15/46) (P < 0.001); accompanied type 0-IIb, 2.1% (2/95) vs 21.7% (10/46) (P < 0.001); and complex type (0-I + IIb, 0-IIa + IIc, etc.), 30.5% (29/95) vs 50.0% (23/46) (P = 0.025). Complex-type s-BEAs had high incidences of T1b invasions and poorly differentiated components (simple type: 22.5% [20/89] and 18.0% [16/89]; complex type: 59.6% [31/52] and 44.2% [23/52], P < 0.001 and P = 0.002, respectively). In SSBE, 72.6% (69/95) of lesions were located at the right anterior wall (P = 0.01). All flat-type or depressed-type lesions derived from SSBE were identified as reddish areas, whereas only 65.2% (15/23) from LSBE were identified as reddish areas (P < 0.001).ConclusionsIn LSBE, flat-type, accompanied-type 0-IIb, and complex-type lesions were significantly more prevalent. Furthermore, complex-type s-BEAs tended to have T1b invasions and poorly differentiated components. S-BEAs in LSBE should be more carefully evaluated on endoscopic appearance including flat-type and complex-type lesions than in SSBE.
| S-EPMC7027738 | biostudies-literature
Project description:Barrett's esophagus (BE) is a known precursor to esophageal adenocarcinoma (EAC). Guidelines recommend BE screening in populations with multiple risk factors, for which non-endoscopic esophageal cell collection with biomarker testing is considered as an acceptable alternative to esophagogastroduodenoscopy (EGD). The aim of this study was to evaluate analytical performance characteristics of EsoGuard® (EG), a DNA methylation biomarker assay, as a laboratory-developed test (LDT) in esophageal samples collected with the swallowable EsoCheck® (EC) device. EG is a next-generation sequencing (NGS) assay that evaluates methylated vimentin (VIM) and cyclin A1 (CCNA1), clinically validated biomarkers for the detection of BE and EAC. The studies were conducted according to standards of College of American Pathology (CAP), Clinical Laboratory Improvement Amendments (CLIA), and New York (NY) state requirements for the analytical validation of molecular assays. Comparison to Sanger sequencing showed that EG was 100% accurate at all 31 CpG sites evaluated by the assay. The analytical sensitivity, specificity, and accuracy of the assay were 89%, 100%, and 96%, respectively. Intra- and inter-assay precision was 100%. The limit of detection (LOD) was 1 in 400 methylated cells, and the reference range was 84%. In summary, EsoGuard demonstrates high analytical accuracy, repeatability, and reproducibility in samples collected using the EsoCheck device.
| S-EPMC11354049 | biostudies-literature
Project description:Interaction between host genotoxic changes and mucosa-associated microbiome (MAM) dysbiosis may have a role in various digestive cancers. We investigated MAM in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) progression sequence and its association with host genotoxic changes. 16S rRNA gene sequencing was performed in three different groups of biopsies from nonneoplastic BE from patients without cancer (N, normal group; n = 47) and with EAC (ADJ, adjacent group; n = 27). Endoscopic biopsies were also obtained from EAC tissues (T, tumor group; n = 22). Results were correlated with TP53 mutation, telomere length and DNA methylation of candidate genes (N33, DPYS, SLC16A12, miR124A3 and miR34bc). Genome-wide DNA methylation examined by reduced representation bisulfite sequencing (RRBS) was available for 32 samples (n = 12 for N, n = 12 for ADJ and n = 22 for T groups). Lower microbial alpha diversity measures were observed in ADJ/T groups relative to N group and associated with higher mean Z score DNA methylation of candidate genes. Specific genera (n = 16) with significant change between ADJ/T groups relative to N group occurred mostly in ADJ group (13/16) and half of them (8/16) were associated with DNA methylation status. Integrated MAM and genome-wide methylation analysis demonstrated that hyper-methylated sites, associated with lower alpha diversity measures dominantly occurred within near the transcription start site, codifying genes were involved in metabolic processes. Our result shows that microbial dysbiosis in EAC mostly occurs in adjacent BE and such dysbiosis was associated with DNA methylation status, offering support for a pathogenic role of interaction between host genotoxic changes and MAM in this tumor type.
| S-EPMC11660833 | biostudies-literature
Project description:Background and aimsEsophageal adenocarcinoma (EAC) incidence has risen dramatically in the Western countries over the past decades. The underlying reasons are incompletely understood, and shifts in the esophageal microbiome have been postulated to increase predisposition to disease development. Multiple factors including medications, lifestyle, and diet could influence microbiome composition and disease progression. The aim of this study was (1) to identify a feasible method to characterize the tissue-associated microbiome, and (2) to investigate differences in the microbiome of saliva, esophageal tissue, and fecal samples by disease state and validate with 2 external cohorts.MethodsForty-eight patients (15 Barrett's esophagus [BE], 4 dysplasia, 15 EAC, and 14 healthy) were enrolled in this cross-sectional study (Munich cohort). Demographics, epidemiologic and clinical data, medications, smoking, and alcohol consumption were assessed. 16S rRNA Gene sequencing was performed on saliva, tissue biopsy and fecal samples. PAXgene fixation was used as a novel methodology. Microbial community alpha- and beta-diversity, as well as microbial composition at phylum and genus level, were characterized for this cohort and compared with 2 external cohorts: New York cohort and Cooperative Health Research in the Augsburg Region cohort.ResultsWe first established PAXgene fixation is a feasible method for microbiome analysis and utilized it to identify a distinct microbial shift in tissue biopsies from patients with EAC, whereas overall microbial diversity in salivary and fecal samples did not differ significantly between disease states. Our findings were similar in a reanalysis to those from a US cohort that used a standardized fresh frozen biopsy collection protocol (New York cohort, N = 75 biopsies). Nevertheless, we could not distinguish German Munich cohort patients from a German population-based cohort (Cooperative Health Research in the Augsburg Region cohort, N = 2140 individuals) when fecal bacterial profiles were compared between both cohorts. In addition, we used data integration of diagnosis and risk factors of patients and found associations with microbiome alterations.ConclusionSample collection and microbiome analysis are indeed feasible and can be implemented into clinical routine by an easy-to-use biopsy protocol. The presence of BE and EAC together with epidemiologic factors can be associated with alterations of the salivary, tissue, and fecal microbial community in an easy-to-use data integration concept. Given a possible role of the microbiome in BE and EAC, it will be important in future studies to take tissue-specific microbial communities and individual taxa into account in larger prospective studies.
| S-EPMC11307671 | biostudies-literature
Project description:Background & aimsRadiofrequency ablation (RFA) is commonly used to treat Barrett's esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality.MethodsWe collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality.ResultsAmong 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA.ConclusionsBased on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.
| S-EPMC4785890 | biostudies-literature