Table 3.

Studies of oesophageal microbiota on oesophageal squamous cell carcinoma.

References	Participants	Sample type	Method	Results
Pei et al. [73]	Four persons with gastrointestinal symptoms	Four distal oesophageal biopsies with normal oesophageal histology	16S rDNA PCR	Six phyla, 41 genera including 13 common genera among 4 persons, and 95 SLOTU including 14 common SLOTU among 4 persons.
Yang et al. [77]	Twelve normal oesophagus, 12 oesophagitis, 10 Barrett’s oesophagus	34 biopsy samples of distal oesophagus.	16S rRNA gene amplification and clone sequencing	Nine phyla, 70 genera and 166 SLOTU; Type I microbiome dominated by Streptococcus in normal oesophagus; Type II microbiome represented by Gram-negative anaerobes in esophagitis and Barrett’s oesophagus
Yu et al. [78]	333 subjects including 142 with ESD and 191 without ESD from Linxian (Linzhou), Henan, China	Upper digestive tract cell samples collected by inflatable rubber balloon covered with cotton mesh or Cytomesh Oesophageal Cytology Device	Human Oral Microbe Identification Microarray for detection of 272 bacterial species.	An inverse association between microbial richness and ESD, and a positive association between microbial richness and PGI/II ratio.
Yang et al.[79]	18 patients with ESCC and 11 volunteers with physiological normal oesophagus from Guangzhou, China	18 ESCC samples and 11 biopsy samples with normal oesophagus	PCR amplification of V4 region of 16S rDNA and sequencing	ESCC tissues had significantly decreased microbial diversity and high abundances of Bacteroidetes, Fusobacteria and Spirochaetes, which were associated with reduced nitrate reductase and nitrite reductase function
Shao et al. [81]	67 patients with ESCC and from Linzhou, Henan, China	Paired ESCC tissue and non-tumour tissue samples	PCR amplification of V4region of 16S rDNA and sequencing	Microbial composition of ESCC comprised of Firmicutes, Bacteroidetes and Proteobacteria phyla; ESCC contained higher abundance of Fusobacteria phylum including Fusobacterium genus, and less abundance of Firmicutes phylum including Streptococcus genus in comparison with non-tumour tissues; ESCC harboured greater abundances of Fusobacteria and Tenericutes phyla, greater abundances of Mycoplasma and Fusobacterium genera in comparison with GCA tumour tissues.
Narikiyo et al. [60]	58 patients with oesophageal cancer from Tokyo, Japan, 4 from China, 2 from France, 5 from Italy.	Oesophageal cancer tissues with or without paired normal tissues.	16S rRNA gene amplification and clone sequencing	Frequent infection of the oral periodontopathic spirochete Treponema denticola, Streptococcus mitis, Streptococcus anginosus in ESCC from different regions of the world.
Yamamura, et al. [62]	325 patients with oesophageal cancer from Kumamoto, Japan	Formalin-fixed, paraffin-embedded (FFPE) oesophageal cancer tissues including 300 ESCCs, 12 adenocarcinomas and 13 of others	qPCR quantification of Fusobacterium nucleatum	F. nucleatum positivity in tumour is 23% (74/325) and is positively correlated with tumour stage. F. nucleatum-positive patients showed poor prognosis with multivariate HR: 1.98 (1.14-3.37)
Yamamura, et al. [63]	551 cases with ESCC	A training cohort of 207 cases with fresh frozen tissues and a validation cohort of 344 cases with FFPE tissues from Nagoya, Kumamoto, Japan, respectively.	qPCR quantification of Fusobacterium nucleatum	High levels of F. nucleatum in ESCC associate with an invasion depth, poor recurrence-free survival, poor chemotherapeutic response
Gao et al. [61]	100 patients with ESCC	100 ESCCs with paired nontumor tissues, and 30 biopsy samples or normal oesophagus from Henan,	Immunohistochemistry and qPCR of 16S rDNA	Porphyromonas gingivalis positivity was 61% in ESCC, 12% in adjacent tissues, and negative in normal oesophagus. High burden of P. gingivalis in ESCC was
		China		positively correlated with poor differentiation, lymph node metastasis, advanced TNM stage, and poor overall survival.
Gao et al. [90]	Patients with ESCC or esophagitis, and healthy controls.	96 cases with ESCC, 50 cases with esophagitis, and 80 healthy controls.	ELISA to measure the serum IgG and IgA antibodies against P. gingivalis.	Serum levels of IgG and IgA against P. gingivalis were higher in ESCC patients than those in patients with esophagitis and healthy controls. Higher levels of IgG and IgA were associated with poor prognosis.

Note: SLOTU denotes species-level operational taxonomic units.