Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients

R. Naddaf; H. Shmilovich; S. Carasso; R. Keshet-David; R. Herren; T. Gefen; T. Goshen-Lago; Y. Zwang; I. Livyatan; N. Shental; O. Haberfeld; R. Straussman; S. R. Markar; M. Nilsson; H. Kashtan; I. Ben-Aharon; N. Geva-Zatorsky

doi:10.1016/j.esmogo.2025.100172

Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients

R. Naddaf
, H. Shmilovich
, S. Carasso
, R. Keshet-David
, R. Herren
, T. Gefen
, T. Goshen-Lago
, Y. Zwang
, I. Livyatan
, N. Shental
, O. Haberfeld
, R. Straussman
, S. R. Markar
, M. Nilsson
, H. Kashtan
, I. Ben-Aharon
, N. Geva-Zatorsky^*

^*Corresponding author for this work

Department of Molecular Cell Biology

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Despite continuous improvement in long-term survival after esophagectomy, potential serious post-operative complications, such as anastomotic leaks (ALs), still occur. Several risk factors for ALs have been proposed, including environmental factors. Our main objective was to examine the correlation of esophageal tumor microbiome composition and functional profile with ALs. Additionally, we analyzed the microbiome of esophageal tumors and their potential correlation with clinical features of the patients. Materials and methods: Surgical specimens of esophageal tumors and adjacent normal tissues were collected from consecutive patients who underwent an esophagectomy. Formalin-fixed paraffin-embedded (FFPE) tissue samples were processed using 16S ribosomal DNA multiple fragments amplicon sequencing to characterize bacterial microbiome composition. The tumor and normal tissue microbiome and bacterial functional profile were analyzed based on the clinical outcome of ALs. Results: Out of 60 patients who met the inclusion criteria, 52 (86.7%) patients had both normal adjacent tissue (NAT) and tumor (T) FFPE samples included with sufficient bacterial DNA extracted for analysis. A total of 28% of participants had esophageal ALs. Proportion tests [P < 0.05, false discovery rate (FDR) < 0.25] revealed operational taxonomic units (OTUs) significantly present in T samples as opposed to NAT samples, as well as significantly present OTUs in patients with AL as opposed to patients without AL complication. Conclusions: In this study, we provide a profile of the understudied esophageal microbiome and its connection to ALs. Our results can provide potential clues on how to avoid ALs by considering a patient's personal microbiome when providing perioperative care.

Original language	English
Article number	100172
Journal	ESMO Gastrointestinal Oncology
Volume	8
Early online date	20 May 2025
DOIs	https://doi.org/10.1016/j.esmogo.2025.100172
Publication status	Published - Jun 2025

Funding

This work was supported by the Technion Institute of Technology (no grant number), ‘Keren Hanasi’ (no grant number), Cathedra (no grant number), the Rappaport Technion Integrated Cancer Center (no grant number) , the Alon Fellowship for Outstanding Young Researchers (no grant number), the Israeli Science Foundation [grant numbers 1571/17, 3165/20], the Seerave Foundation (no grant number) , the Israel Cancer Research Fund Research Career Development Award (no grant number), the Canadian Institute for Advanced Research ( CIFAR ) [grant numbers FL-000969 / FL-001245 / FL-001381 / FL-001656 ], the Human Frontier Science Program Career Development Award [grant number CDA00025/2019-C], the Gutwirth foundation award, the D. Dan and Betty Kahn Foundation’s gift to the University of Michigan , Weizmann Institute, Technion– Israel Institute of Technology Collaboration for Research (no grant number), and the European Union (ERC, ExtractABact, views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.) [grant number 101078712]. N.G.-Z. is a CIFAR fellow in the Humans and the Microbiome Program, a Kavli fellow, and a Horec fellow (Taub Foundation). S.C. is supported by the Gutwirth Excellence Scholarship. We thank the Geva-Zatorsky Lab for fruitful discussions and contributions. We thank Shaked Ahissar for helping with organizing the samples once received from medical centers, and Amalfi Qarawani for helping with DNA preparation. This work was supported by the Technion Institute of Technology (no grant number), ‘Keren Hanasi’ (no grant number), Cathedra (no grant number), the Rappaport Technion Integrated Cancer Center (no grant number), the Alon Fellowship for Outstanding Young Researchers (no grant number), the Israeli Science Foundation [grant numbers 1571/17, 3165/20], the Seerave Foundation (no grant number), the Israel Cancer Research Fund Research Career Development Award (no grant number), the Canadian Institute for Advanced Research (CIFAR) [grant numbers FL-000969/FL-001245/FL-001381/FL-001656], the Human Frontier Science Program Career Development Award [grant number CDA00025/2019-C], the Gutwirth foundation award, the D. Dan and Betty Kahn Foundation's gift to the University of Michigan, Weizmann Institute, Technion–Israel Institute of Technology Collaboration for Research (no grant number), and the European Union (ERC, ExtractABact, views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.) [grant number 101078712]. N.G.-Z. is a CIFAR fellow in the Humans and the Microbiome Program, a Kavli fellow, and a Horec fellow (Taub Foundation). S.C. is supported by the Gutwirth Excellence Scholarship. The authors have declared no conflicts of interest.

All Science Journal Classification (ASJC) codes

Oncology(nursing)
Genetics
Epidemiology
Gastroenterology

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10.1016/j.esmogo.2025.100172Licence: CC BY-NC-ND

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Naddaf, R., Shmilovich, H., Carasso, S., Keshet-David, R., Herren, R., Gefen, T., Goshen-Lago, T., Zwang, Y., Livyatan, I., Shental, N., Haberfeld, O., Straussman, R., Markar, S. R., Nilsson, M., Kashtan, H., Ben-Aharon, I., & Geva-Zatorsky, N. (2025). Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients. ESMO Gastrointestinal Oncology, 8, Article 100172. https://doi.org/10.1016/j.esmogo.2025.100172

@article{f3aa3b4fc935424f8c37320c808f34eb,

title = "Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients",

abstract = "Background: Despite continuous improvement in long-term survival after esophagectomy, potential serious post-operative complications, such as anastomotic leaks (ALs), still occur. Several risk factors for ALs have been proposed, including environmental factors. Our main objective was to examine the correlation of esophageal tumor microbiome composition and functional profile with ALs. Additionally, we analyzed the microbiome of esophageal tumors and their potential correlation with clinical features of the patients. Materials and methods: Surgical specimens of esophageal tumors and adjacent normal tissues were collected from consecutive patients who underwent an esophagectomy. Formalin-fixed paraffin-embedded (FFPE) tissue samples were processed using 16S ribosomal DNA multiple fragments amplicon sequencing to characterize bacterial microbiome composition. The tumor and normal tissue microbiome and bacterial functional profile were analyzed based on the clinical outcome of ALs. Results: Out of 60 patients who met the inclusion criteria, 52 (86.7\%) patients had both normal adjacent tissue (NAT) and tumor (T) FFPE samples included with sufficient bacterial DNA extracted for analysis. A total of 28\% of participants had esophageal ALs. Proportion tests [P < 0.05, false discovery rate (FDR) < 0.25] revealed operational taxonomic units (OTUs) significantly present in T samples as opposed to NAT samples, as well as significantly present OTUs in patients with AL as opposed to patients without AL complication. Conclusions: In this study, we provide a profile of the understudied esophageal microbiome and its connection to ALs. Our results can provide potential clues on how to avoid ALs by considering a patient's personal microbiome when providing perioperative care.",

author = "R. Naddaf and H. Shmilovich and S. Carasso and R. Keshet-David and R. Herren and T. Gefen and T. Goshen-Lago and Y. Zwang and I. Livyatan and N. Shental and O. Haberfeld and R. Straussman and Markar, \{S. R.\} and M. Nilsson and H. Kashtan and I. Ben-Aharon and N. Geva-Zatorsky",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = jun,

doi = "10.1016/j.esmogo.2025.100172",

language = "English",

volume = "8",

journal = "ESMO Gastrointestinal Oncology",

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Naddaf, R, Shmilovich, H, Carasso, S, Keshet-David, R, Herren, R, Gefen, T, Goshen-Lago, T, Zwang, Y , Livyatan, I, Shental, N, Haberfeld, O, Straussman, R, Markar, SR, Nilsson, M, Kashtan, H, Ben-Aharon, I & Geva-Zatorsky, N 2025, 'Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients', ESMO Gastrointestinal Oncology, vol. 8, 100172. https://doi.org/10.1016/j.esmogo.2025.100172

TY - JOUR

T1 - Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients

AU - Naddaf, R.

AU - Shmilovich, H.

AU - Carasso, S.

AU - Keshet-David, R.

AU - Herren, R.

AU - Gefen, T.

AU - Goshen-Lago, T.

AU - Zwang, Y.

AU - Livyatan, I.

AU - Shental, N.

AU - Haberfeld, O.

AU - Straussman, R.

AU - Markar, S. R.

AU - Nilsson, M.

AU - Kashtan, H.

AU - Ben-Aharon, I.

AU - Geva-Zatorsky, N.

PY - 2025/6

Y1 - 2025/6

N2 - Background: Despite continuous improvement in long-term survival after esophagectomy, potential serious post-operative complications, such as anastomotic leaks (ALs), still occur. Several risk factors for ALs have been proposed, including environmental factors. Our main objective was to examine the correlation of esophageal tumor microbiome composition and functional profile with ALs. Additionally, we analyzed the microbiome of esophageal tumors and their potential correlation with clinical features of the patients. Materials and methods: Surgical specimens of esophageal tumors and adjacent normal tissues were collected from consecutive patients who underwent an esophagectomy. Formalin-fixed paraffin-embedded (FFPE) tissue samples were processed using 16S ribosomal DNA multiple fragments amplicon sequencing to characterize bacterial microbiome composition. The tumor and normal tissue microbiome and bacterial functional profile were analyzed based on the clinical outcome of ALs. Results: Out of 60 patients who met the inclusion criteria, 52 (86.7%) patients had both normal adjacent tissue (NAT) and tumor (T) FFPE samples included with sufficient bacterial DNA extracted for analysis. A total of 28% of participants had esophageal ALs. Proportion tests [P < 0.05, false discovery rate (FDR) < 0.25] revealed operational taxonomic units (OTUs) significantly present in T samples as opposed to NAT samples, as well as significantly present OTUs in patients with AL as opposed to patients without AL complication. Conclusions: In this study, we provide a profile of the understudied esophageal microbiome and its connection to ALs. Our results can provide potential clues on how to avoid ALs by considering a patient's personal microbiome when providing perioperative care.

AB - Background: Despite continuous improvement in long-term survival after esophagectomy, potential serious post-operative complications, such as anastomotic leaks (ALs), still occur. Several risk factors for ALs have been proposed, including environmental factors. Our main objective was to examine the correlation of esophageal tumor microbiome composition and functional profile with ALs. Additionally, we analyzed the microbiome of esophageal tumors and their potential correlation with clinical features of the patients. Materials and methods: Surgical specimens of esophageal tumors and adjacent normal tissues were collected from consecutive patients who underwent an esophagectomy. Formalin-fixed paraffin-embedded (FFPE) tissue samples were processed using 16S ribosomal DNA multiple fragments amplicon sequencing to characterize bacterial microbiome composition. The tumor and normal tissue microbiome and bacterial functional profile were analyzed based on the clinical outcome of ALs. Results: Out of 60 patients who met the inclusion criteria, 52 (86.7%) patients had both normal adjacent tissue (NAT) and tumor (T) FFPE samples included with sufficient bacterial DNA extracted for analysis. A total of 28% of participants had esophageal ALs. Proportion tests [P < 0.05, false discovery rate (FDR) < 0.25] revealed operational taxonomic units (OTUs) significantly present in T samples as opposed to NAT samples, as well as significantly present OTUs in patients with AL as opposed to patients without AL complication. Conclusions: In this study, we provide a profile of the understudied esophageal microbiome and its connection to ALs. Our results can provide potential clues on how to avoid ALs by considering a patient's personal microbiome when providing perioperative care.

UR - https://www.scopus.com/pages/publications/105010881718

U2 - 10.1016/j.esmogo.2025.100172

DO - 10.1016/j.esmogo.2025.100172

M3 - Article

AN - SCOPUS:105010881718

SN - 2949-8198

VL - 8

JO - ESMO Gastrointestinal Oncology

JF - ESMO Gastrointestinal Oncology

M1 - 100172

ER -

Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients

Abstract

Funding

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