Skip to main content
NCBI home page
Journal of Neurogastroenterology and Motility logoLink to Journal of Neurogastroenterology and Motility
editorial
. 2020 Apr 30;26(2):171–179. doi: 10.5056/jnm19240

Exploring Esophageal Microbiomes in Esophageal Diseases: A Systematic Review

Chan Hyuk Park 1, Sang Kil Lee 2,*
PMCID: PMC7176507  PMID: 32235026

Abstract

Studies that investigated esophageal microbiomes are limited when compared to those on intestinal microbiomes. Nevertheless, several studies have investigated the relationship between esophageal microbiomes and various esophageal diseases, owing to the advancement of next-generation sequencing techniques. Streptococcus is the most common bacterial taxon in a normal esophagus. Additionally, Haemophilus, Neisseria, Prevotella, and Veillonella are also found. However, gram-negative bacteria, including Prevotella, are more abundant in a diseased esophagus, such as in gastroesophageal reflux disease and Barrett’ esophagus. This systematic review aims to summarize current evidences on esophageal microbiomes in various esophageal diseases.

Keywords: Barrett esophagus, Eosinophilic esophagitis, Esophageal neoplasms, Gastroesophageal reflux, Microbiota

Introduction

While intestinal microbiomes have been relatively well studied, upper gastrointestinal tract microbiomes have not been thoroughly evaluated. Especially, studies on esophageal microbiomes are relatively limited. Traditionally, the esophagus is regarded as devoid of a significant bacterial population.1,2 In addition, microbial flora in a normal esophagus has been considered transient and translocated from the oropharynx.3 In 1998, Gagliardi et al3 revealed that Streptococcus viridans is the most commonly found microorganism in esophageal cultures, which is also isolated from oropharyngeal cultures.

However, next-generation sequencing techniques such as 16S ribosomal RNA (rRNA) gene sequencing have been increasingly used to open a new horizon for microbial research nowadays.4 The technique allowed recognition of uncultured bacteria, facilitating easy identification of differences in microbial composition between a normal and diseased esophagus.5 Currently, the esophagus has been found to contain a diverse microbiome.6,7 Additionally, several studies evaluated the microbial composition of a normal esophagus as well as various esophageal diseases such as gastroesophageal reflux disease (GERD), Barrett’s esophagus, esophageal cancer, and eosinophilic esophagitis (EoE).2 Here, we performed a systematic review on the variation in microbial composition according to the esophageal diseases.

Methods

Search Strategy

We searched for all relevant studies published between January 1980 and February 2020 that examined the human esophageal microbiome using the MEDLINE, EMBASE, and Cochrane Library databases. The following search string was used: ([esophagus] OR [oesophagus] OR [esophageal] OR [oesophageal]) AND ([microbiome] OR [microbiota] OR [microbial] OR [microflora] OR [biota] OR [bacterial flora] OR [bacterial biofilm]). Appendix 1 shows the detailed search strategies in each database.

Inclusion/Exclusion Criteria

The inclusion criteria were as follows: (1) healthy individuals or patients with esophageal diseases including GERD, esophageal cancer, EoE, and achalasia, and (2) composition or any other findings about the esophageal microbiome. Non-original studies, non-human studies, abstract-only publications, and studies published in languages other than English were excluded.

Study Selection

First, we reviewed the titles and abstracts of the research papers found during our keyword search. Duplicates from multiple search engines were removed. Next, irrelevant studies were excluded by title and abstract review according to our inclusion and exclusion criteria. We screened the full text of all remaining studies. Two investigators (C.H.P. and S.K.L.) independently evaluated the studies for eligibility. Any disagreements were resolved through discussion and consensus.

Data Extraction

Data were extracted using a data extraction form that had been developed in advance. Two investigators (C.H.P. and S.K.L.) independently extracted the following information: first author, year of publication, country, study period, population, publication language, and study outcomes.

Results

Study Selection

Figure 1 shows the study flow diagram for our systematic review. Our literature search identified 682 studies. After examining the titles and abstracts, we discarded 200 duplicate articles, which were retrieved through multiple search engines. Another 444 irrelevant articles were excluded on the basis of their titles and abstracts. After reviewing the full text of the 38 remaining articles, we further excluded 5 articles that did not report the relevant outcomes. Additionally, 1 non-original article and 2 articles in which full-texts were unavailable were excluded. Finally, 30 studies were included in the systematic review.3,5,6,8-34 The main findings about esophageal microbiome of these studies are summarized in Table.

Microbiome in a Normal Esophagus

The first study on microbiomes in a normal esophagus, based on bacterial cultures, was conducted by Mannell et al9 in 1983. In their study, S. viridans, Haemophilus influenzae, Neisseria catarrhalis, Streptococcus group B, Streptococcus faecalis, and Klebsiella pneumonia were commonly isolated in aspirates from the normal esophagus. They also demonstrated that the esophagus is unsterile. The following studies also revealed that various bacteria can be found in a normal esophagus. In 1998, Gagliardi et al3 tried to culture aspirate samples from 30 patients with nonspecific dyspepsia. Among them, S. viridans was most commonly found and isolated from 9 samples (30.0%). Group D Streptococcus, Enterococcus, Staphylococcus aureus, and Klebsiella were also isolated (20.0%, 10.0%, 6.6%, and 6.6%, respectively). In that study, S. viridans as well as Neisseria, non-group D Streptococcus were identified (45.5%, 27.3%, and 18.2%, respectively) in the oropharynx. Although the sample size was limited, the isolated bacteria in the esophagus were similar to those in the oropharynx, but not identical. Recently, Norder Grusell et al5 investigated the bacteria found in both upper and lower esophagus through esophageal biopsy and brush. In their study, the most common cultured bacteria were S. viridans, followed by Fusobacterium, Neisseria, Haemophilus, and Prevotella, regardless of their location in the esophagus.

Since the early 2000s, esophageal microbiomes have been evaluated using culture-independent methods. Pei et al6 examined esophageal biopsy samples obtained from 4 individuals. They performed a broad-range 16S rRNA gene polymerase chain reaction (PCR) analysis and obtained 900 PCR cloned products representing 833 unique sequences belonging to 41 genera. A majority of clones belonged to 13 of 41 genera, which were shared by all 4 individuals.6 Specifically, Streptococcus (39.0%), Prevotella (17.0%), and Veillonella (14.0%) were most prevalent.6 In 2012, Fillon et al14 evaluated the esophageal microbiome in 15 individuals to investigate the performance of an esophageal string test (Enterotest) as compared to biopsy in the collected esophageal mucosal samples. They investigated the bacterial composition using the 16S rRNA gene sequencing technique. and they showed that the most prevalent bacterial taxa were Streptococcus, Prevotella, and Veillonella, which were similar with samples obtained through biopsy and those obtained through the esophageal string test.

In summary, the most common bacterial taxa in a normal esophagus include Streptococcus, Haemophilus, Neisseria, Prevotella, and Veillonella. However, the bacterial composition may differ depending on various factors, even in a normal esophagus. Age is the best-known factor associated with the esophageal microbiome,25 which was positively correlated with Streptococcus, but negatively correlated with Prevotella in the Deshpande et al study25 that investigated the bacterial community in the esophageal microbiome of 106 individuals. It is not yet clear why age affects the composition of esophageal microbiomes. However, the influence of age on the composition of gastric microbiomes has been also known.35 Chronic gastric inflammation and decreased intragastric acidity by aging may change the microbial composition of the stomach. Given that gastric contents can affect the esophageal mucosa, change of gastric microbiome caused by aging may result in change of esophageal microbiomes.

Additionally, proton pump inhibitors (PPIs) may also affect esophageal microbiomes. Amir et al17 showed a significant change of esophageal microbiomes after 8 weeks of PPI treatment (unweighted UniFrac analysis of similarities R = 0.17, P < 0.05). Decreased acid reflux by PPI administration may affect the esophageal microbiomes. Diet can also influence the esophageal microbiomes. In a previous study, dietary fiber intake was associated with increased number of Firmicutes and decreased number of gram-negative bacteria.27 Conversely, low fiber intake was associated with a high number of gram-negative bacteria, including Prevotella, Neisseria, and Eikenella. It has been known that low fiber diet can lead to weight gain,36 while high fiber diet may increase the production of short-chain fatty acid in the colon and improve systematic insulin sensitivity.37 These changes may be related to the impact of dietary fiber on the esophageal microbiome.

The impact of low fiber intake is similar to that of reflux esophagitis or Barrett's esophagus on the esophageal microbiome composition, which will be described in the next section.

Reflux Diseases and Esophageal Microbiomes

In addition to demographic factors and medications, various diseases affect the esophageal microbial composition. In a study on gastric microbiomes, bacterial taxa other than Helicobacter pylori were hardly identified in patients infected with H. pylori.38 Highly abundant H. pylori itself may be one of the causes; however, the acidic environment of the stomach is another cause for the decrease in number of other bacteria. In patients with severe atrophy and intestinal metaplasia, which decreased the intragastric acidity, various bacteria other than H. pylori are found.39 Therefore, the esophageal microbial composition can easily be considered to change in patients with GERD and Barrett's esophagus.

In 2009, Yang et al13 suggested that the esophageal microbiome could be classified into 2 groups: type I microbiome dominated by Gram-positive taxa of Firmicutes phylum in normal individuals, and type II microbiome dominated by gram-negative taxa in patients with GERD and Barrett's esophagus. They concluded that inflammation and intestinal metaplasia are related with esophageal microbiome alteration. The main bacterial taxa in type I microbiome was Streptococcus, whereas type II microbiomes included Veillonella, Prevotella, Haemophilus, Neisseria, Rothia, Granulicatella, Campylobacter, Porphyromonas, Fusobacterium, and Actinomyces. As previously indicated, Haemophilus, Neisseria, Prevotella, and Veillonella are also commonly identified in the normal esophagus. In other words, the type II microbiomes are not exclusively found in a normal esophagus. They have a high probability to be found in an acid-exposed esophagus. Deshpande et al25 classified bacterial taxa into several clusters. Among various bacterial taxa, Streptococcus and Prevotella were the representative bacterial taxa of clusters they belonged to.25 Moreover, they revealed that the interaction between Streptococcus and Prevotella was consistently found in a co-exclusion interaction. These findings are consistent with results in the Yang et al study.13 Another study suggested that the Streptococcus-to-Prevotella ratio was also a risk factor for the development of Barrett's esophagus.19

The difference in esophageal microbiome among the reflux disease status was also shown in the Liu et al study,16 conducted using 16S rRNA gene sequencing. Streptococcus was the most common bacterial taxa in all the following 3 groups: normal esophagus, reflux esophagitis, and Barrett's esophagus. However, the proportion of Streptococcus was slightly higher in the normal group than in the reflux esophagitis or Barrett's esophagus groups. Pasteurella, Haemophilus, Fusobacterium, Prevotella, and Neisseria were more abundant in the reflux esophagitis group than in the normal group.

In another study by Blackett et al15 conducted using a cultural analysis with PCR for specific bacterial taxa, the abundance of Campylobacter was increased in patients with GERD or Barrett's esophagus. Additionally, a significant increase in IL-18 expression was shown in esophagus colonized by Campylobacter among patients with GERD or Barrett's esophagus. IL-18 is known as an IFN-γ-inducing factor and plays a primary role in both innate and adaptive immunity.40 Although the causal relationship has not been fully evaluated, an interplay between the esophageal microbiome and inflammatory markers is possible.

Based on results of these previous studies, the schematic diagram on differences in esophageal microbiome composition was observed according to the disease status in Figure 2.

Esophageal Cancer and Esophageal Microbiome

In contrast to changes toward increasing various bacterial taxa in GERD and Barrett's esophagus, microbial diversity decreased in esophageal adenocarcinoma (EAC) when compared with the control, which enriched acid-tolerant bacteria such as Lactobacillus fermentum.23 EAC development may change peritumoral microenvironment including acidity. The production of lactic acid may also further acidify the intraesophageal environment. Additionally, noxious products from these bacteria, including hydrogen peroxide, may directly inhibit the growth of other bacteria and enable Lactobacillus to dominate in the lower esophagus.23 A study by Snider et al32 also showed that microbial diversity decreased in patients with EAC. The proportion of Firmicutes phylum (including Streptococcus) increased in the low-grade dysplasia, as compared to high-grade dysplasia or adenocarcinoma. In this study, the proportion of Enterobacteriaceae and Akkermansia increased and Veillonella decreased in patients with EAC.

Until recently, characteristics of the esophageal microbiome in patients with esophageal squamous cell carcinoma (ESCC) have not been well known. However, in a recent case-control study including 25 patients with ESCC and 50 matched controls, Prevotella, especially Prevotella nanceiensis, was abundant in patients with ESCC.24 Interestingly, Porphyromonas gingivalis, a periodontal pathogen, tended to increase in patients with ESCC. In a study on the oral microbiome in patients with ESCC, Porphyromonas was abundant in patients with ESCC as compared to those with dysplasia as well as the normal controls.41 An association of Fusobacterium nucleatum, one of the periodontal bacteria, with the risk of colorectal cancer has been proven.42 Another study by Shao et al31 evaluated the difference in the esophageal microbiome between patients with ESCC and those with gastric cardia adenocarcinoma (GCA). Patients with ESCC showed a high proportion of Fusobacteria phylum (ESCC: 3.9% and GCA: 1.9%). Additionally, the microbiome in esophageal cancer tissue may be used for prediction of patient's prognosis. In the previous studies, intratumoral F. nucleatum was associated with poor recurrence-free survival as well as cancer-specific survival in patients with esophageal cancer.22,33

Eosinophilic Esophagitis and Esophageal Microbiome

EoE is a chronic immune/antigen-mediated disorder caused by T helper 2-mediated immune response triggered by food or environmental allergens.43,44 As an increase in incidence and prevalence of EoE, interest in the esophageal microbiome in patients with EoE has been increasing.43 In patients with EoE, Neisseria and Corynebacterium were enriched as compared to those with non-EoE.21 In another study by Harris et al,20 the bacterial load was increased regardless of the treatment status or degree of mucosal eosinophilia in patients with EoE as compared to healthy individuals. Haemophilus was significantly abundant in patients with untreated EoE.20

Achalasia and Esophageal Microbiome

Achalasia is a motility disorder presented as dysphagia, regurgitation of undigested food, weight loss, and chest pain.45 It is caused by the inability to lower the esophageal sphincter to facilitate relaxation in the setting of absent peristalsis.46 The relationship between achalasia and esophageal microbiome has not been evaluated. Although several case reports showed the association between Mycobacterium goodii pulmonary infection and achalasia and secondary achalasia due to human immunodeficiency viral infection,47,48 evidence that support the association between achalasia and microbial composition in the esophagus of patients with achalasia were limited.

Conclusion

Owing to the advancement of next-generation sequencing techniques, associations between the esophageal microbiomes and various diseases have been widely investigated. Nowadays, the esophagus is found to be unsterile, and many bacterial taxa exist depending on the disease status. However, whether the esophageal microbiome induces esophageal diseases remains unknown. Most changes in esophageal microbiome composition may likely be a secondary change due to acid reflux, aggravation of inflammation, and other predisposing factors such as alcohol and smoking. To determine the causal relationship between esophageal microbiome and diseases, well-designed experiments using germ-free animal models are warranted. Nevertheless, understanding the esophageal microbiome in various diseases may have a clinical implication because oral microbiomes are usually correlated with esophageal microbiomes. We will be able to predict various esophageal diseases via oral samples that can be easily obtained compared to esophageal samples. Further researches will be conducted on oral and esophageal microbiomes in various esophageal diseases.

Fig. 1.

Fig. 1

Open in a new tab

The study flow diagram.

Fig. 2.

Fig. 2

Open in a new tab

Schematic diagram of differences in esophageal microbiome composition according to esophageal diseases. GERD, gastroesophageal reflux disease; BE, Barrett’s esophagus; EAC, esophageal adenocarcinoma; ESCC, esophageal squamous cell carcinoma; EoE, eosinophilic esophagitis.

Table 1.

Summary of Studies on Esophageal Microbiome

Study Country Study period Population Analysis Main findings about esophageal microbiome
1982, Finlay et al8 UK N/A 12 patients with esophageal cancer Culture Streptococcus, Coagulase-negative Staphylococcus, and Lactobacillus were prevalent in patients with esophageal cancer.
1983, Mannell et al9 South Africa N/A 50 individuals without esophageal disease, 51 patients with esophageal cancer Culture Streptococcus viridans, Haemophilus influenzae, and Klebsiella pneumoniae were abundant in both individuals with normal esophagus and patients with esophageal cancer.
1998, Gagliardi et al3 Brazil N/A 30 patients with dyspepsia Culture Streptococcus viridans and group D Streptococcus were prevalent in patients with dyspepsia.
2004, Pei et al6 USA N/A 4 normal individuals 16S rRNA gene sequencing Streptococcus, Prevotella, and Veillonella were most prevalent in the esophageal microbiome.
2005, Pei et al10 USA N/A 9 normal individuals, 12 patients with GERD, 3 patients with BE 16S rRNA gene sequencing Bacteroidetes, Proteobacteria, and Firmicutes were abundant in the esophageal microbiome.
2007, Macfarlane et al11 UK N/A 7 individuals with gastrointestinal symptoms requiring endoscopic examination, 7 patients with BE Culture, 16S rRNA gene sequencing Campylobacter was abundant in patients with BE, while it was not identified in patients with control.
2007, Zilberstein et al12 Brazil N/A 10 normal individuals Culture Streptococcus (40.0%), Staphylococcus (20.0%), Corynebacterium (10.0%), Lactobacillus (10.0%), and Peptococcus (10.0%) were identified in the esophagus.
2009, Yang et al13 USA N/A 12 normal individuals, 12 patients with esophagitis, 10 patients with BE 16S rRNA gene sequencing Type I microbiome, dominated by the Streptococcus, correlated with normal esophagus, while type II microbiome contained a greater proportion of gram-negative anaerobes/microaerophiles correlated with esophagitis.
2012, Fillon et al14 USA N/A 15 pediatric individuals who scheduled upper endoscopy 16S rRNA gene sequencing Streptococcus, Prevotella, and Veillonella were most prevalent in the esophageal microbiome.
2013, Blackett et al15 Scotland N/A 39 patients with iron deficiency anemia, 37 patients with GERD, 45 patients with BE Culture Campylobacter was prevalent in patients with GERD or BE compared to the control (patients with iron deficiency anemia).
2013, Liu et al16 Japan 2008-2009 6 normal individuals, 6 patients with reflux esophagitis, 6 patients with BE 16S rRNA gene sequencing Proteobacteria was most prevalent in normal individuals (49.0%) and patients with reflux esophagitis (43.0%), while Firmicutes was most prevalent in patients with BE.
2013, Norder Grusell et al5 Sweden 2006-2009 40 individuals without gastrointestinal disease Culture Streptococccus Viridans was most prevalent in the esophagus.
2014, Amir et al17 Israel N/A 15 individuals with normal esophageal mucosa, 13 patients with esophagitis, 6 patients with BE 16S rRNA gene sequencing Enterobacteriaceae was associated with an abnormal esophagus. Proton pump inhibitor treatment changes the composition of esophageal microbiome.
2014, Yu et al18 China 2002 192 subjects without esophageal squamous dysplasia, 142 patients with esophageal squamous dysplasia Human Oral Microbe Identification Microarray Lower microbial richness was associated with the presence of esophageal squamous dysplasia.
2015, Gall et al19 USA 1983-2008 12 patients with BE 16S rRNA gene sequencing Streptococcus to Prevotella species ratio was associated with progression of Barrett's esophagus.
2015, Harris et al20 USA N/A 25 normal individuals, 8 patients with GERD, 37 patients with EoE 16S rRNA gene sequencing Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibitor as compared with normal subjects.
2015, Benitez et al21 USA N/A 35 non-EoE pediatric individuals, 33 pediatric patients with EoE 16S rRNA gene sequencing Proteobacteria including Neisseria and Corynebacterium was enriched in patients with EoE, while Firmicutes was predominant in non-EoE pediatric individuals.
2016, Yamamura et al22 Japan 2005-2013 325 patients with esophageal cancer Polymerase chain reaction Fusobacterium nucleatum in esophageal cancer tissues was associated with shorter survival.
2017, Elliott et al23 UK N/A 20 normal individuals, 24 patients with non-dysplastic BE, 23 patients with dysplastic BE, 19 patients with BAC 16S rRNA gene sequencing Lactobacillus fermentum was enriched in esophageal adenocarcinoma. Microbial diversity in patients with high-grade dysplasia decreased in comparison to control.
2017, Peters et al24 USA N/A 210 normal individuals, 81 patients with EAC, 25 patients with ESCC 16S rRNA gene sequencing Decreased abundance of Neisseria and Streptococcus pneumoniae was associated with lower risk of EAC. Porphyromonas gingivalis tended to be associated with higher risk of ESCC.
2018, Deshpande et al25 Australia N/A 106 patients with gastrointestinal symptoms 16S rRNA gene sequencing The interaction between Streptococcus mitis/oralis/pneumoniae and Prevotella spp. was found to be a co-exclusion interaction. The ratio of Streptococcus to Prevotella is an important defining characteristic across esophageal community types.
2018, Dong et al26 China 2015 27 normal individuals 16S rRNA gene sequencing Streptococcus was more prevalent in the esophagus than in the oral cavity.
2018, Nobel et al27 USA N/A 47 ambulatory patients scheduled to undergo endoscopy 16S rRNA gene sequencing Increasing fiber intake was significantly associated with increasing relative abundance of Firmicutes.
2019, Liu et al28 China 2015-2016 67 patients with ESCC 16S rRNA gene sequencing Mucosal swab specimens and biopsies yielded similar microbial profiles in patients with ESCC.
2019, Okereke et al29 USA N/A 12 patients with BE 16S rRNA gene sequencing Streptococcus were widespread throughout the esophagus (from proximal to distal esophagus).
2019, Okereke et al30 USA N/A 17 patients with BE 16S rRNA gene sequencing Streptococcus and Alloiococcus were more prevalent in the esophagus compared to the uvular.
2019, Shao et al31 China 2015 67 patients with ESCC 16S rRNA gene sequencing The abundance of Fusobacterium was increased, while that of Streptococcus was decreased in the tumor tissues compared to non-tumor tissues in patients with ESCC.
2019, Snider et al32 USA N/A 16 normal individuals, 14 patients with non-dysplastic BE, 10 patients with dysplastic BE, 4 patients with BAC 16S rRNA gene sequencing Patients with high-grade dysplasia or adenocarcinoma increased Enterobacteriaceae and Akkermansia muciniphila and reduced Veillonella. Patients taking proton pump inhibitors increased Streptococcus and decreased Gram-negative bacteria.
2019, Yamamura et al33 Japan 2001-2016 551 patients with ESCC Polymerase chain reaction High burden of F. nucleatum was associated with poor recurrence-free survival in patients with ESCC.
2019, Yu et al34 China 2017 17 normal individuals, 32 patients with reflux esophagitis 16S rRNA gene sequencing The richness and diversity of esophageal microbiome tended to be decreased in patients with reflux esophagitis.
Open in a new tab

N/A, not available; rRNA, ribosomal RNA; GERD, gastroesophageal reflux disease; BE, Barrett's esophagus; BAC, Barrett's adenocarcinoma; ESCC, esophageal squamous cell carcinoma; EoE, eosinophilic esophagitis.

Footnotes

Financial support: None.

Conflicts of interest: None.

Author contributions: Chan Hyuk Park performed the literature search and drafted and revised the article; Sang Kil Lee conceived and revised the article; and Chan Hyuk Park and Sang Kil Lee approved the final version of the manuscript.

REFERENCES

  1. Yang L, Chaudhary N, Baghdadi J, Pei Z. Microbiome in reflux disorders and esophageal adenocarcinoma. Cancer J. 2014;20:207–210. doi: 10.1097/PPO.0000000000000044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Corning B, Copland AP, Frye JW. The esophageal microbiome in health and disease. Curr Gastroenterol Rep. 2018;20:39. doi: 10.1007/s11894-018-0642-9. [DOI] [PubMed] [Google Scholar]
  3. Gagliardi D, Makihara S, Corsi PR, et al. Microbial flora of the normal esophagus. Dis Esophagus. 1998;11:248–250. doi: 10.1093/dote/11.4.248. [DOI] [PubMed] [Google Scholar]
  4. Bik EM, Eckburg PB, Gill SR, et al. Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci USA. 2006;103:732–737. doi: 10.1073/pnas.0506655103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Norder Grusell E, Dahlén G, Ruth M, et al. Bacterial flora of the human oral cavity, and the upper and lower esophagus. Dis Esophagus. 2013;26:84–90. doi: 10.1111/j.1442-2050.2012.01328.x. [DOI] [PubMed] [Google Scholar]
  6. Pei Z, Bini EJ, Yang L, Zhou M, Francois F, Blaser MJ. Bacterial biota in the human distal esophagus. Proc Natl Acad Sci USA. 2004;101:4250–4255. doi: 10.1073/pnas.0306398101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. May M, Abrams JA. Emerging insights into the esophageal microbiome. Curr Treat Options Gastroenterol. 2018;16:72–85. doi: 10.1007/s11938-018-0171-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Finlay IG, Wright PA, Menzies T, McArdle CS. Microbial flora in carcinoma of oesophagus. Thorax. 1982;37:181–184. doi: 10.1136/thx.37.3.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mannell A, Plant M, Frolich J. The microflora of the oesophagus. Ann R Coll Surg Engl. 1983;65:152–154. [PMC free article] [PubMed] [Google Scholar]
  10. Pei Z, Yang L, Peek RM, Jr Levine SM, Jr, Pride DT, Blaser MJ. Bacterial biota in reflux esophagitis and Barrett's esophagus. World J Gastroenterol. 2005;11:7277–7283. doi: 10.3748/wjg.v11.i46.7277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Macfarlane S, Furrie E, Macfarlane GT, Dillon JF. Microbial colonization of the upper gastrointestinal tract in patients with Barrett's esophagus. Clin Infect Dis. 2007;45:29–38. doi: 10.1086/518578. [DOI] [PubMed] [Google Scholar]
  12. Zilberstein B, Quintanilha AG, Santos MA, et al. Digestive tract microbiota in healthy volunteers. Clinics (Sao Paulo) 2007;62:47–54. doi: 10.1590/S1807-59322007000100008. [DOI] [PubMed] [Google Scholar]
  13. Yang L, Lu X, Nossa CW, Francois F, Peek RM, Pei Z. Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome. Gastroenterology. 2009;137:588–597. doi: 10.1053/j.gastro.2009.04.046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fillon SA, Harris JK, Wagner BD, et al. Novel device to sample the esophageal microbiome--the esophageal string test. PLoS One. 2012;7:e42938. doi: 10.1371/journal.pone.0042938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Blackett KL, Siddhi SS, Cleary S, et al. Oesophageal bacterial biofilm changes in gastro-oesophageal reflux disease, Barrett's and oesophageal carcinoma: association or causality? Aliment Pharmacol Ther. 2013;37:1084–1092. doi: 10.1111/apt.12317. [DOI] [PubMed] [Google Scholar]
  16. Liu N, Ando T, Ishiguro K, et al. Characterization of bacterial biota in the distal esophagus of Japanese patients with reflux esophagitis and Barrett's esophagus. BMC Infect Dis. 2013;13:130. doi: 10.1186/1471-2334-13-130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Amir I, Konikoff FM, Oppenheim M, Gophna U, Half EE. Gastric microbiota is altered in oesophagitis and Barrett's oesophagus and further modified by proton pump inhibitors. Environ Microbiol. 2014;16:2905–2914. doi: 10.1111/1462-2920.12285. [DOI] [PubMed] [Google Scholar]
  18. Yu G, Gail MH, Shi J, et al. Association between upper digestive tract microbiota and cancer-predisposing atates in the esophagus and stomach. Cancer Epidemiol Biomarkers Prev. 2014;23:735–741. doi: 10.1158/1055-9965.EPI-13-0855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gall A, Fero J, McCoy C, et al. Bacterial composition of the human upper gastrointestinal tract microbiome is dynamic and associated with genomic instability in a Barrett's esophagus cohort. PLoS One. 2015;10:e0129055. doi: 10.1371/journal.pone.0129055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Harris JK, Fang R, Wagner BD, et al. Esophageal microbiome in eosinophilic esophagitis. PLoS One. 2015;10:e0128346. doi: 10.1371/journal.pone.0128346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Benitez AJ, Hoffmann C, Muir AB, et al. Inflammation-associated microbiota in pediatric eosinophilic esophagitis. Microbiome. 2015;3:23. doi: 10.1186/s40168-015-0085-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yamamura K, Baba Y, Nakagawa S, et al. Human microbiome Fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis. Clin Cancer Res. 2016;22:5574–5581. doi: 10.1158/1078-0432.CCR-16-1786. [DOI] [PubMed] [Google Scholar]
  23. Elliott DRF, Walker AW, O'Donovan M, Parkhill J, Fitzgerald RC. A non-endoscopic device to sample the oesophageal microbiota: a case-control study. Lancet Gastroenterol Hepatol. 2017;2:32–42. doi: 10.1016/S2468-1253(16)30086-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Peters BA, Wu J, Pei Z, et al. Oral microbiome composition reflects prospective risk for esophageal cancers. Cancer Res. 2017;77:6777–6787. doi: 10.1158/0008-5472.CAN-17-1296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Deshpande NP, Riordan SM, Castaño-Rodríguez N, Wilkins MR, Kaakoush NO. Signatures within the esophageal microbiome are associated with host genetics, age, and disease. Microbiome. 2018;6:227. doi: 10.1186/s40168-018-0611-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Dong L, Yin J, Zhao J, et al. Microbial similarity and preference for specific sites in healthy oral cavity and esophagus. Front Microbiol. 2018;9:1603. doi: 10.3389/fmicb.2018.01603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nobel YR, Snider EJ, Compres G, et al. Increasing dietary fiber intake is associated with a distinct esophageal microbiome. Clin Transl Gastroenterol. 2018;9:199. doi: 10.1038/s41424-018-0067-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Liu AQ, Vogtmann E, Shao DT, et al. A comparison of biopsy and mucosal swab specimens for examining the microbiota of upper gastrointestinal carcinoma. Cancer Epidemiol Biomarkers Prev. 2019;28:2030–2037. doi: 10.1158/1055-9965.EPI-18-1210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Okereke I, Hamilton C, Reep G, et al. Microflora composition in the gastrointestinal tract in patients with Barrett's esophagus. J Thorac Dis. 2019;11(suppl 12):S1581–S1587. doi: 10.21037/jtd.2019.06.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Okereke IC, Miller AL, Hamilton CF, et al. Microbiota of the oropharynx and endoscope compared to the esophagus. Sci Rep. 2019;9:10201. doi: 10.1038/s41598-019-46747-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shao D, Vogtmann E, Liu A, et al. Microbial characterization of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-risk region of China. Cancer. 2019;125:3993–4002. doi: 10.1002/cncr.32403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Snider EJ, Compres G, Freedberg DE, et al. Alterations to the esophageal microbiome associated with progression from Barrett's esophagus to esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2019;28:1687–1693. doi: 10.1158/1055-9965.EPI-19-0008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yamamura K, Izumi D, Kandimalla R, et al. Intratumoral Fusobacterium nucleatum levels predict therapeutic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma. Clin Cancer Res. 2019;25:6170–6179. doi: 10.1158/1078-0432.CCR-19-0318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yu Y, Gao F, Chen X, Zheng S, Zhang J. Changes in the distal esophageal microbiota in Chinese patients with reflux esophagitis. J Dig Dis. 2019;20:18–24. doi: 10.1111/1751-2980.12692. [DOI] [PubMed] [Google Scholar]
  35. Park CH, Lee JG, Lee AR, Eun CS, Han DS. Network construction of gastric microbiome and organization of microbial modules associated with gastric carcinogenesis. Sci Rep. 2019;9:12444. doi: 10.1038/s41598-019-48925-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ludwig DS, Pereira MA, Kroenke CH, et al. Dietary fiber, weight gain, and cardiovascular disease risk factors in young adults. JAMA. 1999;282:1539–1546. doi: 10.1001/jama.282.16.1539. [DOI] [PubMed] [Google Scholar]
  37. Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015;11:577–591. doi: 10.1038/nrendo.2015.128. [DOI] [PubMed] [Google Scholar]
  38. Park CH, Lee AR, Lee YR, Eun CS, Lee SK, Han DS. Evaluation of gastric microbiome and metagenomic function in patients with intestinal metaplasia using 16S rRNA gene sequencing. Helicobacter. 2019;24:e12547. doi: 10.1111/hel.12547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Choi S, Lee JG, Lee AR, Eun CS, Han DS, Park CH. Helicobacter pylori antibody and pepsinogen testing for predicting gastric microbiome abundance. PLoS One. 2019;14:e0225961. doi: 10.1371/journal.pone.0225961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Pages F, Berger A, Lebel-Binay S, et al. Proinflammatory and antitumor properties of interleukin-18 in the gastrointestinal tract. Immunol Lett. 2000;75:9–14. doi: 10.1016/S0165-2478(00)00285-6. [DOI] [PubMed] [Google Scholar]
  41. Chen X, Winckler B, Lu M, et al. Oral microbiota and risk for esophageal squamous cell carcinoma in a high-risk area of china. PLoS One. 2015;10:e0143603. doi: 10.1371/journal.pone.0143603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lauritano D, Sbordone L, Nardone M, Iapichino A, Scapoli L, Carinci F. Focus on periodontal disease and colorectal carcinoma. Oral Implantol (Rome) 2017;10:229–233. doi: 10.11138/orl/2017.10.3.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Dellon ES. The esophageal microbiome in eosinophilic esophagitis. Gastroenterology. 2016;151:364–365. doi: 10.1053/j.gastro.2016.06.026. [DOI] [PubMed] [Google Scholar]
  44. Rothenberg ME. Molecular, genetic, and cellular bases for treating eosinophilic esophagitis. Gastroenterology. 2015;148:1143–1157. doi: 10.1053/j.gastro.2015.02.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Boeckxstaens GE, Zaninotto G, Richter JE. Achalasia. Lancet. 2014;383:83–93. doi: 10.1016/S0140-6736(13)60651-0. [DOI] [PubMed] [Google Scholar]
  46. Pandolfino JE, Gawron AJ. Achalasia: a systematic review. JAMA. 2015;313:1841–1852. doi: 10.1001/jama.2015.2996. [DOI] [PubMed] [Google Scholar]
  47. Martínez-González D, Franco J, Navarro-Ortega D, Muñoz C, Martí-Obiol R, Borrás-Salvador R. Achalasia and mycobacterium goodii pulmonary infection. Pediatr Infect Dis J. 2011;30:447–448. doi: 10.1097/INF.0b013e3182024c1c. [DOI] [PubMed] [Google Scholar]
  48. Wang AJ, Tu LX, Yu C, Zheng XL, Hong JB, Lu NH. Achalasia secondary to cardial tuberculosis caused by AIDS. J Dig Dis. 2015;16:752–753. doi: 10.1111/1751-2980.12287. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurogastroenterology and Motility are provided here courtesy of The Korean Society of Neurogastroenterology and Motility

RESOURCES