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Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis

Immune checkpoint inhibitors (ICIs) have become the standard of care for several cancers. However, ICI therapy has also been associated with various immune-related adverse events (irAEs). Clinical manifestations of immune-related colitis resemble those of inflammatory bowel diseases such as ulcerati...

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Autores principales: Sakai, Kazuko, Sakurai, Toshiharu, De Velasco, Marco A., Nagai, Tomoyuki, Chikugo, Takaaki, Ueshima, Kazuomi, Kura, Yurie, Takahama, Takayuki, Hayashi, Hidetoshi, Nakagawa, Kazuhiko, Kudo, Masatoshi, Nishio, Kazuto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578892/
https://www.ncbi.nlm.nih.gov/pubmed/34778085
http://dx.doi.org/10.3389/fonc.2021.763468
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author Sakai, Kazuko
Sakurai, Toshiharu
De Velasco, Marco A.
Nagai, Tomoyuki
Chikugo, Takaaki
Ueshima, Kazuomi
Kura, Yurie
Takahama, Takayuki
Hayashi, Hidetoshi
Nakagawa, Kazuhiko
Kudo, Masatoshi
Nishio, Kazuto
author_facet Sakai, Kazuko
Sakurai, Toshiharu
De Velasco, Marco A.
Nagai, Tomoyuki
Chikugo, Takaaki
Ueshima, Kazuomi
Kura, Yurie
Takahama, Takayuki
Hayashi, Hidetoshi
Nakagawa, Kazuhiko
Kudo, Masatoshi
Nishio, Kazuto
author_sort Sakai, Kazuko
collection PubMed
description Immune checkpoint inhibitors (ICIs) have become the standard of care for several cancers. However, ICI therapy has also been associated with various immune-related adverse events (irAEs). Clinical manifestations of immune-related colitis resemble those of inflammatory bowel diseases such as ulcerative colitis (UC). The composition of the bowel microflora is thought to influence the development of inflammatory bowel disease and irAE colitis. We profiled the gene expressions and microbe compositions of colonic mucosa from patients with solid cancers receiving anti-PD-L1 antibody treatment; we then compared the expression profiles associated with irAE colitis with those associated with UC. The pathway enrichment analysis revealed functional similarities between inflamed regions of irAE colitis and UC. The common enriched pathways included leukocyte extravasation and immune responses, whereas non-inflamed mucosa from patients with irAE colitis was distinct from patients with UC and was characterized by the recruitment of immune cells. A similarity between the microbiota profiles was also identified. A decreased abundance of Bacteroides species was observed in inflamed regions from both irAE colitis and UC based on a microbiota composition analysis of 16S rDNA sequencing. Pathways associated with molecule transport systems, including fatty acids, were enriched in inflamed and non-inflamed irAE colitis and inflamed UC, similar to Piphillin-inferred KEGG pathways. While UC is characterized by local regions of inflammation, ICI treatment extends to non-inflammatory regions of the colonial mucosa where immune cells are reconstituted. This analysis of the similarity and heterogeneity of irAE colitis and UC provides important information for the management of irAE colitis.
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spelling pubmed-85788922021-11-11 Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis Sakai, Kazuko Sakurai, Toshiharu De Velasco, Marco A. Nagai, Tomoyuki Chikugo, Takaaki Ueshima, Kazuomi Kura, Yurie Takahama, Takayuki Hayashi, Hidetoshi Nakagawa, Kazuhiko Kudo, Masatoshi Nishio, Kazuto Front Oncol Oncology Immune checkpoint inhibitors (ICIs) have become the standard of care for several cancers. However, ICI therapy has also been associated with various immune-related adverse events (irAEs). Clinical manifestations of immune-related colitis resemble those of inflammatory bowel diseases such as ulcerative colitis (UC). The composition of the bowel microflora is thought to influence the development of inflammatory bowel disease and irAE colitis. We profiled the gene expressions and microbe compositions of colonic mucosa from patients with solid cancers receiving anti-PD-L1 antibody treatment; we then compared the expression profiles associated with irAE colitis with those associated with UC. The pathway enrichment analysis revealed functional similarities between inflamed regions of irAE colitis and UC. The common enriched pathways included leukocyte extravasation and immune responses, whereas non-inflamed mucosa from patients with irAE colitis was distinct from patients with UC and was characterized by the recruitment of immune cells. A similarity between the microbiota profiles was also identified. A decreased abundance of Bacteroides species was observed in inflamed regions from both irAE colitis and UC based on a microbiota composition analysis of 16S rDNA sequencing. Pathways associated with molecule transport systems, including fatty acids, were enriched in inflamed and non-inflamed irAE colitis and inflamed UC, similar to Piphillin-inferred KEGG pathways. While UC is characterized by local regions of inflammation, ICI treatment extends to non-inflammatory regions of the colonial mucosa where immune cells are reconstituted. This analysis of the similarity and heterogeneity of irAE colitis and UC provides important information for the management of irAE colitis. Frontiers Media S.A. 2021-10-27 /pmc/articles/PMC8578892/ /pubmed/34778085 http://dx.doi.org/10.3389/fonc.2021.763468 Text en Copyright © 2021 Sakai, Sakurai, De Velasco, Nagai, Chikugo, Ueshima, Kura, Takahama, Hayashi, Nakagawa, Kudo and Nishio https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Sakai, Kazuko
Sakurai, Toshiharu
De Velasco, Marco A.
Nagai, Tomoyuki
Chikugo, Takaaki
Ueshima, Kazuomi
Kura, Yurie
Takahama, Takayuki
Hayashi, Hidetoshi
Nakagawa, Kazuhiko
Kudo, Masatoshi
Nishio, Kazuto
Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis
title Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis
title_full Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis
title_fullStr Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis
title_full_unstemmed Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis
title_short Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis
title_sort intestinal microbiota and gene expression reveal similarity and dissimilarity between immune-mediated colitis and ulcerative colitis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578892/
https://www.ncbi.nlm.nih.gov/pubmed/34778085
http://dx.doi.org/10.3389/fonc.2021.763468
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