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The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs)
Gut microbiome balance plays a key role in human health and maintains gut barrier integrity. Dysbiosis, referring to impaired gut microbiome, is linked to a variety of diseases, including cancers, through modulation of the inflammatory process. Most studies concentrated on adenocarcinoma of differen...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164086/ https://www.ncbi.nlm.nih.gov/pubmed/35678665 http://dx.doi.org/10.3390/cimb44050136 |
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author | Mohamed, Amr Asa, Sylvia L. McCormick, Thomas Al-Shakhshir, Hilmi Dasari, Arvind Mauricio, Retuerto Salem, Iman Ocuin, Lee M. Bajor, David Lee, Richard T. Selfridge, J. Eva Kardan, Arash Lee, Zhenghong Avril, Norbert Kopp, Shelby Winter, Jordan M. Hardacre, Jeffrey M. Ammori, John B. Ghannoum, Mahmoud A. |
author_facet | Mohamed, Amr Asa, Sylvia L. McCormick, Thomas Al-Shakhshir, Hilmi Dasari, Arvind Mauricio, Retuerto Salem, Iman Ocuin, Lee M. Bajor, David Lee, Richard T. Selfridge, J. Eva Kardan, Arash Lee, Zhenghong Avril, Norbert Kopp, Shelby Winter, Jordan M. Hardacre, Jeffrey M. Ammori, John B. Ghannoum, Mahmoud A. |
author_sort | Mohamed, Amr |
collection | PubMed |
description | Gut microbiome balance plays a key role in human health and maintains gut barrier integrity. Dysbiosis, referring to impaired gut microbiome, is linked to a variety of diseases, including cancers, through modulation of the inflammatory process. Most studies concentrated on adenocarcinoma of different sites with very limited information on gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we have analyzed the gut microbiome (both fungal and bacterial communities) in patients with metastatic GEP-NENs. Fecal samples were collected and compared with matched healthy control samples using logistic regression distances utilizing R package MatchIt (version 4.2.0, Daniel E. Ho, Stanford, CA, USA). We examined differences in microbiome profiles between GEP-NENs and control samples using small subunit (SSU) rRNA (16S), ITS1, ITS4 genomic regions for their ability to accurately characterize bacterial and fungal communities. We correlated the results with different behavioral and dietary habits, and tumor features including differentiation, grade, primary site, and therapeutic response. All tests are two-sided and p-values ≤ 0.05 were considered statistically significant. Gut samples of 34 patients (12 males, 22 females, median age 64 years) with metastatic GEP-NENs (22 small bowel, 10 pancreatic, 1 gall bladder, and 1 unknown primary) were analyzed. Twenty-nine patients had well differentiated GEP-neuroendocrine tumors (GEP-NETs), (G1 = 14, G2 = 12, G3 = 3) and five patients had poorly differentiated GEP-neuroendocrine carcinomas (GEP-NECs). Patients with GEP-NENs had significantly decreased bacterial species and increased fungi (notably Candida species, Ascomycota, and species belonging to saccharomycetes) compared to controls. Patients with GEP-NECs had significantly enriched populations of specific bacteria and fungi (such as Enterobacter hormaechei, Bacteroides fragilis and Trichosporon asahii) compared to those with GEP-NETs (p = 0.048, 0.0022 and 0.034, respectively). In addition, higher grade GEP-NETs were associated with significantly higher Bacteroides fragilis (p = 0.022), and Eggerthella lenta (p = 0.00018) species compared to lower grade tumors. There were substantial differences associated with dietary habits and therapeutic responses. This is the first study to analyze the role of the microbiome environment in patients with GEP-NENs. There were significant differences between GEP-NETs and GEP-NECs, supporting the role of the gut microbiome in the pathogenesis of these two distinct entities. |
format | Online Article Text |
id | pubmed-9164086 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91640862022-06-04 The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs) Mohamed, Amr Asa, Sylvia L. McCormick, Thomas Al-Shakhshir, Hilmi Dasari, Arvind Mauricio, Retuerto Salem, Iman Ocuin, Lee M. Bajor, David Lee, Richard T. Selfridge, J. Eva Kardan, Arash Lee, Zhenghong Avril, Norbert Kopp, Shelby Winter, Jordan M. Hardacre, Jeffrey M. Ammori, John B. Ghannoum, Mahmoud A. Curr Issues Mol Biol Article Gut microbiome balance plays a key role in human health and maintains gut barrier integrity. Dysbiosis, referring to impaired gut microbiome, is linked to a variety of diseases, including cancers, through modulation of the inflammatory process. Most studies concentrated on adenocarcinoma of different sites with very limited information on gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we have analyzed the gut microbiome (both fungal and bacterial communities) in patients with metastatic GEP-NENs. Fecal samples were collected and compared with matched healthy control samples using logistic regression distances utilizing R package MatchIt (version 4.2.0, Daniel E. Ho, Stanford, CA, USA). We examined differences in microbiome profiles between GEP-NENs and control samples using small subunit (SSU) rRNA (16S), ITS1, ITS4 genomic regions for their ability to accurately characterize bacterial and fungal communities. We correlated the results with different behavioral and dietary habits, and tumor features including differentiation, grade, primary site, and therapeutic response. All tests are two-sided and p-values ≤ 0.05 were considered statistically significant. Gut samples of 34 patients (12 males, 22 females, median age 64 years) with metastatic GEP-NENs (22 small bowel, 10 pancreatic, 1 gall bladder, and 1 unknown primary) were analyzed. Twenty-nine patients had well differentiated GEP-neuroendocrine tumors (GEP-NETs), (G1 = 14, G2 = 12, G3 = 3) and five patients had poorly differentiated GEP-neuroendocrine carcinomas (GEP-NECs). Patients with GEP-NENs had significantly decreased bacterial species and increased fungi (notably Candida species, Ascomycota, and species belonging to saccharomycetes) compared to controls. Patients with GEP-NECs had significantly enriched populations of specific bacteria and fungi (such as Enterobacter hormaechei, Bacteroides fragilis and Trichosporon asahii) compared to those with GEP-NETs (p = 0.048, 0.0022 and 0.034, respectively). In addition, higher grade GEP-NETs were associated with significantly higher Bacteroides fragilis (p = 0.022), and Eggerthella lenta (p = 0.00018) species compared to lower grade tumors. There were substantial differences associated with dietary habits and therapeutic responses. This is the first study to analyze the role of the microbiome environment in patients with GEP-NENs. There were significant differences between GEP-NETs and GEP-NECs, supporting the role of the gut microbiome in the pathogenesis of these two distinct entities. MDPI 2022-04-30 /pmc/articles/PMC9164086/ /pubmed/35678665 http://dx.doi.org/10.3390/cimb44050136 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mohamed, Amr Asa, Sylvia L. McCormick, Thomas Al-Shakhshir, Hilmi Dasari, Arvind Mauricio, Retuerto Salem, Iman Ocuin, Lee M. Bajor, David Lee, Richard T. Selfridge, J. Eva Kardan, Arash Lee, Zhenghong Avril, Norbert Kopp, Shelby Winter, Jordan M. Hardacre, Jeffrey M. Ammori, John B. Ghannoum, Mahmoud A. The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs) |
title | The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs) |
title_full | The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs) |
title_fullStr | The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs) |
title_full_unstemmed | The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs) |
title_short | The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs) |
title_sort | role of the microbiome in gastroentero-pancreatic neuroendocrine neoplasms (gep-nens) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164086/ https://www.ncbi.nlm.nih.gov/pubmed/35678665 http://dx.doi.org/10.3390/cimb44050136 |
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