Objective  To investigate the characteristics and diversity of paracancerous tissue microbiota among esophageal squamous cell carcinoma (ESCC) patients from different regions of Fujian province for providing evidences to ESCC prevention.

  Methods   Totally 120 ESCC patients were recruited after radical surgery at two municipal hospitals in two cities of Fujian province from February 2013 through October 2017. All the participants were pathologically diagnosed primary ESCC cases with local residential history of more than 10 years and with intact para-cancerous tissue/exact tumor stage/complete medical records and but without infectious disease/other primary malignant, without antimicrobial therapy/radiotherapy/ chemotherapy during two months before the surgery and without specific medicine use during one month before the surgery. A face-to-face questionnaire interview was conducted in the participants. Double-ended sequencing with 16S rRNA V3-V4 variable region was performed for para-cancerous tissue specimens. The paracancerous tissue microbiota diversity and composition were analyzed with QIIME2019.4. Multivariate unconditional logistic regression was used to assess the association of residential region with patients' paracancerous tissue microbiota.

  Results   Of the 120 participants, 105 were from 4 prefectures (Zhangzhou,Fuzhou, Putian and Quanzhou prefecture) and only 15 participants from other 5 prefectures of the province. There were no significantly differences in gender, age, smoking, alcohol and tea consumption, sampling season and tumor site among the participants from various regions (all P > 0.05); while the alpha- and beta-diversity in paracancerous tissue microbiota were significantly different among the participants from various regions (both P < 0.05). The abundance of para-cancerous esophageal microbiota of 15 phyla, 22 classes, 28 orders, 48 families, 71 genera, and 85 species were calculated with QIIME 2019.4. After adjusting for confounding factors including gender, age, smoking, alcohol consumption, tea consumption, sampling seasons and tumor location, the multivariate unconditional logistic regression analysis of dominant microbiota showed that the abundance of order Rickettsiales and family mitochondria detected in the participants from Fuzhou were higher than those in the participants from Zhangzhou; while the abundance of order Sphingomonadales, family Ruminococcaceae and Sphingomonadaceae, genus Faecalibacterium and Sphingomonas detected in the participants from Fuzhou were lower than those in the participants from Zhangzhou; the abundance of class Actinobacteria, order Caulobacterales and Sphingomonadales, family Ruminococcaceae, Caulobacteraceae and Sphingomonadaceae, and genus Sphingomonas in detected in the participants from Putian were lower than those in the participants from Zhangzhou; the abundance of phylum OD1, order Rickettsiales and family mitochondria in the participants from Quanzhou were higher than those in the participants from Zhangzhou; the abundance of order Coriobacteriales, Caulobacterales and Sphingomonadales, family Ruminococcaceae, Caulobacteraceae, Sphingomonadaceae, and Coriobacteriaceae, and genus Faecalibacterium in the participants from Quanzhou were lower than those in the participants from Zhangzhou; the abundance of class Coriobacteriia, order Coriobacteriales and Caulobacterales, family Ruminococcaceae, Caulobacteraceae and Coriobacteriaceae, and genus Faecalibacterium in the participants from other regions were lower than those in the participants from Zhangzhou. After adjusting for gender, age, smoking, alcohol consumption, tea consumption, sampling season and tumor site, the multivariate unconditional logistic regression analysis on rare microbiota showed that the abundance of phylum Verrucomicrobia, class Verrucomicrobiae, order Verrucomicrobiales, family Verrucomicrobiaceae, genus Roseburia, Mycoplana and Akkermansia, and species muciniphila were more likely to be lower in the participants from Fuzhou in comparison with the participants from Zhangzhou; the abundance of phylum Verrucomicrobia, class Verrucomicrobiae, order Verrucomicrobiales, family Verrucomicrobiaceae, genus Blautia, Roseburia, Mycoplana and Akkermansia, and species Longicatena and Muciniphila were more likely to be lower in the participants from Putian, Quzhou and other regions compared to the participants from Zhangzhou.

  Conclusion   Residential region is an influencing factor for paracancerous tissue microbiota among ESCC patients.