Dataset Information

The Salivary Microbiome and Predicted Metabolite Production Are Associated with Barrett's Esophagus and High-Grade Dysplasia or Adenocarcinoma.

ABSTRACT:

Background

Esophageal adenocarcinoma (EAC) is rising in incidence, and established risk factors do not explain this trend. Esophageal microbiome alterations have been associated with Barrett's esophagus (BE) and dysplasia and EAC. The oral microbiome is tightly linked to the esophageal microbiome; this study aimed to identify salivary microbiome-related factors associated with BE, dysplasia, and EAC.

Methods

Clinical data and oral health history were collected from patients with and without BE. The salivary microbiome was characterized, assessing differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features. Microbiome metabolic modeling was used to predict metabolite production.

Results

A total of 244 patients (125 non-BE and 119 BE) were analyzed. Patients with high-grade dysplasia (HGD)/EAC had a significantly higher prevalence of tooth loss (P = 0.001). There were significant shifts with increased dysbiosis associated with HGD/EAC, independent of tooth loss, with the largest shifts within the genus Streptococcus. Modeling predicted significant shifts in the microbiome metabolic capacities, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production in HGD/EAC.

Conclusions

Marked dysbiosis in the salivary microbiome is associated with HGD and EAC, with notable increases within the genus Streptococcus and accompanying changes in predicted metabolite production. Further work is warranted to identify the biological significance of these alterations and to validate metabolic shifts.

Impact

There is an association between oral dysbiosis and HGD/EAC. Further work is needed to establish the diagnostic, predictive, and causal potential of this relationship.

SUBMITTER: Solfisburg QS

PROVIDER: S-EPMC10955687 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

The Salivary Microbiome and Predicted Metabolite Production Are Associated with Barrett's Esophagus and High-Grade Dysplasia or Adenocarcinoma.

Solfisburg Quinn S QS Baldini Federico F Baldwin-Hunter Brittany B Austin George I GI Lee Harry H HH Park Heekuk H Freedberg Daniel E DE Lightdale Charles J CJ Korem Tal T Abrams Julian A JA

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20240301 3

<h4>Background</h4>Esophageal adenocarcinoma (EAC) is rising in incidence, and established risk factors do not explain this trend. Esophageal microbiome alterations have been associated with Barrett's esophagus (BE) and dysplasia and EAC. The oral microbiome is tightly linked to the esophageal microbiome; this study aimed to identify salivary microbiome-related factors associated with BE, dysplasia, and EAC.<h4>Methods</h4>Clinical data and oral health history were collected from patients with a ...[more]

PMID: 38117184

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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.

Project description:Background & aimsBarrett's esophagus (BE) is the greatest risk factor for esophageal adenocarcinoma (EAC), but only a small proportion of patients with BE develop cancer. Biomarkers might be able to identify patients at highest risk of progression. We investigated genomic differences in surveillance biopsies collected from patients whose BE subsequently progressed compared to patients whose disease did not progress.MethodsWe performed a retrospective case-control study of 24 patients with BE that progressed to high-grade dysplasia (HGD, n = 14) or EAC (n = 10). The control group (n = 73, called non-progressors) comprised patients with BE and at least 5 years of total endoscopic biopsy surveillance without progression to HGD or EAC. From each patient, we selected a single tissue sample obtained more than 1 year before progression (cases) or more than 2 years before the end of follow-up (controls). Pathogenic mutations, gene copy numbers, and ploidy were compared between samples from progressors and non-progressors.ResultsTP53 mutations were detected in 46% of samples from progressors and 5% of non-progressors. In this case-control sample set, TP53 mutations in BE tissues increased the adjusted risk of progression 13.8-fold (95% confidence interval, 3.2-61.0) (P < .001). We did not observe significant differences in ploidy or copy-number profile between groups. We identified 147 pathogenic mutations in 57 distinct genes-the average number of pathogenic mutations was higher in samples from progressors (n = 2.5) than non-progressors (n = 1.2) (P < .001). TP53 and other somatic mutations were recurrently detected in samples with limited copy-number changes (aneuploidy).ConclusionsIn genomic analyses of BE tissues from patients with or without later progression to HGD or EAC, we found significantly higher numbers of TP53 mutations in BE from patients with subsequent progression. These mutations were frequently detected before the onset of dysplasia or substantial changes in copy number.

Project description:IntroductionEndoscopic eradication therapy with radiofrequency ablation (RFA) and endoscopic mucosal resection is a safe and effective treatment for Barrett's esophagus. Although the outcomes of surveillance endoscopy after successful endoscopic eradication therapy have been described, no previous studies have modeled the natural history or the effect of surveillance endoscopy after successful ablation to prevent progression to invasive esophageal adenocarcinoma.MethodsThe US RFA Registry is a multicenter registry consisting of patients treated with RFA for Barrett's esophagus at 148 institutions (113 community-based and 35 academic-affiliated). The authors fit models to impute the natural history of recurrence and neoplastic progression after any recurrence or retreatment. Natural history estimates of invasive adenocarcinoma after ablation therapy were compared with as-treated estimates at 5 years to derive the preventive risk difference for surveillance.ResultsNatural history estimates for the postablation progression of high-grade dysplasia (HGD) or intramucosal adenocarcinoma to invasive adenocarcinoma after treatment were 6.3% at 5 years compared with 1.3% for low-grade dysplasia (LGD). The natural history model found a much higher preventative risk difference for surveillance for HGD/intramucosal adenocarcinoma (-4.8%), compared with LGD (-1.1%). The numbers needed to surveil at 5 years were 21 and 90 for these groups, respectively, to prevent one case of invasive esophageal adenocarcinoma, making surveillance after successful ablation of baseline HGD more than 4 times as effective at preventing invasive cancer than after successful ablation of baseline LGD.DiscussionEndoscopic surveillance after successful ablation of baseline HGD or intramucosal cancer is much more effective than surveillance after successful treatment of baseline LGD in averting invasive adenocarcinoma. Although the modest benefits of surveillance for treated LGD may be greater than the risks for patients at average risk for adverse effects of endoscopy, clinicians should concentrate on retaining patients with baseline HGD or cancer in endoscopic surveillance programs.

Dataset Information

The Salivary Microbiome and Predicted Metabolite Production Are Associated with Barrett's Esophagus and High-Grade Dysplasia or Adenocarcinoma.

Background

Methods

Results

Conclusions

Impact

Publications

The Salivary Microbiome and Predicted Metabolite Production Are Associated with Barrett's Esophagus and High-Grade Dysplasia or Adenocarcinoma.

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