Microbiome in Eosinophilic Esophagitis—Metagenomic, Metatranscriptomic, and Metabolomic Changes: A Systematic Review

Background: Our understanding of human gut microbiota has expanded in recent years with the introduction of high-throughput sequencing methods. These technologies allow for the study of metagenomic, metatranscriptomic, and metabolomic bacterial alterations as they relate to human disease. Work in this area has described the human gut microbiome in both healthy individuals and those with chronic gastrointestinal diseases, such as eosinophilic esophagitis (EoE).Objectives: A systematic review of the current available literature on metagenomic, metatranscriptomic, and metabolomic changes in EoE was performed.Methods: This review was performed following the PRISMA guidelines for reporting systematic reviews and meta-analyses. All relevant publications up to March 2021 were retrieved using the search engines PubMed, Google Scholar, and Web of Science. They were then extracted, assessed, and reviewed. Only original studies published in English were included.Results: A total of 46 potential manuscripts were identified for review. Twelve met criteria for further review based on relevance screening and 9 met criteria for inclusion, including 6 studies describing the microbiome in EoE and 3 detailing metabolomic/tissue biochemistry alterations in EoE. No published studies examined metatranscriptomic changes. Samples for microbiome analysis were obtained via esophageal biopsy (n = 3), esophageal string test (n = 1), salivary sampling (n = 1), or stool specimen (n = 1). Samples analyzing tissue biochemistry were obtained via esophageal biopsy (n = 2) and blood plasma (n = 1). There were notable differences in how samples were collected and analyzed. Metabolomic and tissue biochemical alterations were described using Raman spectroscopy, which demonstrated distinct differences in the spectral intensities of glycogen, lipid, and protein content compared to controls. Finally, research in proteomics identified an increase in the pro-fibrotic protein thrombospondin-1 in patients with EoE compared with controls.Conclusions: While there are notable changes in the microbiome, these differ with the collection technique and method of analysis utilized. Techniques characterizing metabolomics and tissue biochemistry are now being utilized to further study patients with EoE. The lack of published data related to the human microbiome, metagenome, metatranscriptome, and metabolome in patients with EoE highlights the need for further research in these areas.

207 ESOPHAGEAL BIOPSY AND SWAB MICROBIAL CHARACTERIZATION WITH HEALTH AND ESOPHAGEAL DISEASE IN CHINA

Little is known about the esophageal microbiota and esophageal health or disease in China, especially esophageal squamous cell precancerous lesions. And there is currently no optimal sampling method for esophageal microbiota. Consequently, we compared microbial signature between and within esophageal biopsy and swab specimens from participants in healthy or with esophageal diseases. Methods A total of 236 subjects were recruited in the Linxian Cancer Hospital (Henan, China), including 5 groups as 70 healthy cases, 70 esophagitis cases, 70 low grade intraepithelial neoplasia (LGIN) cases, 19 high grade intraepithelial neoplasia (HGIN) cases and 7 esophageal squamous cell carcinoma (ESCC) cases. Sterile biopsies and swabs were used to collect paired samples from the same participants under the endoscopy examination. DNA was extracted with the MoBio PowerSoil Kit. Data from 16S rRNA gene sequencing were processed using QIIME2 and R to evaluate differences in alpha and beta diversity and taxonomic relative abundances. Results Alpha diversity was not significantly different between specimens (biopsy = 116.2, swab = 118.0, P > 0.05). In swabs, there were differences of observed OTUs among groups but not Shannon index, detailly, there was an inconspicuous decreasing from Health (125.0) to ESCC (114.0). About beta diversity, no distinct clustering by specimen was observed for weighted Unifrac distance and unweighted Unifrac distance. The 10 dominant genera were similar between specimens and among groups. Specially, Streptococcus was the most abundant except ESCCs; Fusobacterium was in the top ten only in ESCCs. And there was a decreasing of Prevotella 7 and an increasing of Haemophilus as progression. Conclusion Esophageal biopsy and swab specimens could yield similar bacterial composition. Both can be used to find clues of microbiota and disease. And esophageal microbial composition and progression characterizations could provide new idea and basis for large scale, prospective cohort studies in the future.

A Case of Widespread Cutaneous Metastases from Esophageal Adenocarcinoma

Cutaneous metastases from internal malignancies are very rare, and only a few cases from esophageal cancer have been reported. We describe the case of a 61-year-old patient with recently diagnosed esophageal adenocarcinoma who presented with multiple skin nodules. Immunohistochemical analysis of the nodules matched the immunohistochemical profile of the patient’s previous esophageal biopsy specimen confirming the diagnosis of cutaneous metastases. This case highlights the importance of including cutaneous metastases in the differential diagnosis of any suspicious lesion in patients with a history of internal malignancy.

Eosinophil granule major basic protein 1 deposition in eosinophilic esophagitis correlates with symptoms independent of eosinophil counts

SUMMARY In patients with eosinophilic esophagitis (EoE), symptoms often do not correlate with peak eosinophil counts (PEC) determined on histopathological examination of biopsy specimens. This may be because eosinophils degranulate during active disease and lose their morphological identity as intact cells and, therefore, are not enumerated on microscopic examination. Eosinophil granule proteins that are released into tissues with degranulation, including major basic protein 1 (eMBP1), likely contribute to disease pathogenesis and, therefore, may correlate with symptoms better than PEC. We sought to determine whether symptoms in patients with EoE more closely relate to eosinophil granule protein deposition than to eosinophil enumeration, especially in patients with fewer than 15 eosinophils per high power field (HPF). Esophageal biopsy specimens from 34 patients diagnosed with EoE were obtained for histopathological examination and for evaluation of eMBP1 staining by indirect immunofluorescence. PEC by histopathology were compared to extracellular eMBP1 grades by immunostaining. PEC and eMBP1 grades also were analyzed for their relationship to symptoms and clinical course. Biopsy specimens from 19 of the 34 patients had fewer than 15 PEC on histopathological examination, and the other 15 patients had 15 or greater PEC. Positive eMBP1 immunostaining was found in all symptomatic patients. EoE symptoms were related to eMBP1 immunostaining grades (p = 0.0001), but not PEC (P = 0.14). Eosinophil granule protein deposition, specifically eMBP1, is increased in esophageal biopsy specimens from symptomatic patients with EoE and may be a marker of disease activity, including patients with EoE who have ‘resolved’ disease.

DOZ047.76: Eosinophilic esophagitis and esophageal atresia. Is there an association?

Aim of the Study Eosinophilic esophagitis (EoE) is a recently diagnosed entity and seems to be more prevalent in patients with esophageal atresia (EA). It can mimic dysphagia and gastroesophageal reflux (GER) symptoms frequently observed in EA, but treatment is different. Methods Retrospective review (2002–2019) of patients with EA who underwent esophagogastroduodenoscopy (EGD) and esophageal biopsy was performed. EGD was performed in symptomatic patients and in all patients at 12–15 years. Diagnostic criteria for EoE included >15 eosinophils for a high-power field in the esophageal mucosa. Main Results From a total of 110 patients with EA, 27 lost follow-up. In the remaining 83, 56 patients (67, 5%) underwent EGD because of dysphagia or gastroesophageal reflux (GER) studies. Esophageal biopsies were performed in 35 patients and the diagnostic criteria for EoE were achieved in 5 (14,3%). The mean age at diagnosis of EoE was 10 + 2 years and the indication for EGD was GER symptoms (3) or dysphagia (2). In one case an antireflux surgery was previously performed but symptoms slightly persisted, while in 4 cases contrast studies and pH-metry showed no or minimal GER. EGD demonstrated light distal esophagitis in 2 cases, white exudates in 2, and was completely normal in the remaining one. On follow-up, 4 patients remain asymptomatic with proton pump inhibitor medication, and periodic EGD shows macroscopic improvement with a decreased eosinophilic peak on esophageal biopsies. Conclusions Patients with EA seem to have a higher risk of developing EoE at early puberty. EGD on follow-up should be focused not only on studying GER or Barrett, but also on actively search for EoE with an esophageal biopsy, even when the macroscopic appearance is normal.