Cell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity

The gut microbiota (GM) has been shown to be closely associated with the development of colorectal cancer (CRC). However, the involvement of GM is CRC has mainly been demonstrated by metagenomic profiling studies showing the compositional difference between the GM of healthy individuals and that of...

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Autores principales: Byeong Seob Oh, Won Jung Choi, Ji-Sun Kim, Seoung Woo Ryu, Seung Yeob Yu, Jung-Sook Lee, Seung-Hwan Park, Se Won Kang, Jiyoung Lee, Won Yong Jung, Young-Min Kim, Jae-Ho Jeong, Ju Huck Lee
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/a68b317525c24e1ab6618b04593705a3
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spelling oai:doaj.org-article:a68b317525c24e1ab6618b04593705a32021-11-17T11:03:22ZCell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity1664-302X10.3389/fmicb.2021.736343https://doaj.org/article/a68b317525c24e1ab6618b04593705a32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.736343/fullhttps://doaj.org/toc/1664-302XThe gut microbiota (GM) has been shown to be closely associated with the development of colorectal cancer (CRC). However, the involvement of GM is CRC has mainly been demonstrated by metagenomic profiling studies showing the compositional difference between the GM of healthy individuals and that of CRC patients and not by directly studying isolated gut microbes. Thus, to discover novel gut microbes involved in CRC, we isolated the GM from the feces of healthy individuals and evaluated its anti-CRC activity in vitro and in vivo. After GM isolation, cell-free supernatants (CFSs) were prepared from the isolated gut microorganisms to efficiently screen a large amount of the GM for anti-proliferative ability in vitro. Our results showed that the CFSs of 21 GM isolates had anti-proliferative activity against human colon cancer HCT 116 cells. Of these 21 GM isolates, GM07 was chosen for additional study because it had the highest anti-cancer activity against mouse colon cancer CT 26 cells in vitro and was further evaluated in a CT 26 allograft mouse model in vivo. GM07 was identified as Odoribacter splanchnicus through phylogenetic analysis based on 16S rRNA gene sequencing. Further investigation determined that the CFS of O. splanchnicus (OsCFS) induced anti-proliferative activity via apoptosis, but not cell cycle arrest. Moreover, GC/MS analysis suggested that the putative active molecule in OsCFS is malic acid. Finally, in the CRC mouse model, peri-tumoral injection of OsCFS significantly decreased CRC formation, compared to the control group. Altogether, these findings will provide valuable information for the discovery of potential probiotic candidates that inhibit CRC.Byeong Seob OhWon Jung ChoiJi-Sun KimSeoung Woo RyuSeung Yeob YuJung-Sook LeeSeung-Hwan ParkSe Won KangJiyoung LeeWon Yong JungYoung-Min KimJae-Ho JeongJu Huck LeeFrontiers Media S.A.articlegut microbiotaOdoribacter splanchnicuscolorectal cancercell-free supernatantapoptosismurine modelMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic gut microbiota
Odoribacter splanchnicus
colorectal cancer
cell-free supernatant
apoptosis
murine model
Microbiology
QR1-502
spellingShingle gut microbiota
Odoribacter splanchnicus
colorectal cancer
cell-free supernatant
apoptosis
murine model
Microbiology
QR1-502
Byeong Seob Oh
Won Jung Choi
Ji-Sun Kim
Seoung Woo Ryu
Seung Yeob Yu
Jung-Sook Lee
Seung-Hwan Park
Se Won Kang
Jiyoung Lee
Won Yong Jung
Young-Min Kim
Jae-Ho Jeong
Ju Huck Lee
Cell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity
description The gut microbiota (GM) has been shown to be closely associated with the development of colorectal cancer (CRC). However, the involvement of GM is CRC has mainly been demonstrated by metagenomic profiling studies showing the compositional difference between the GM of healthy individuals and that of CRC patients and not by directly studying isolated gut microbes. Thus, to discover novel gut microbes involved in CRC, we isolated the GM from the feces of healthy individuals and evaluated its anti-CRC activity in vitro and in vivo. After GM isolation, cell-free supernatants (CFSs) were prepared from the isolated gut microorganisms to efficiently screen a large amount of the GM for anti-proliferative ability in vitro. Our results showed that the CFSs of 21 GM isolates had anti-proliferative activity against human colon cancer HCT 116 cells. Of these 21 GM isolates, GM07 was chosen for additional study because it had the highest anti-cancer activity against mouse colon cancer CT 26 cells in vitro and was further evaluated in a CT 26 allograft mouse model in vivo. GM07 was identified as Odoribacter splanchnicus through phylogenetic analysis based on 16S rRNA gene sequencing. Further investigation determined that the CFS of O. splanchnicus (OsCFS) induced anti-proliferative activity via apoptosis, but not cell cycle arrest. Moreover, GC/MS analysis suggested that the putative active molecule in OsCFS is malic acid. Finally, in the CRC mouse model, peri-tumoral injection of OsCFS significantly decreased CRC formation, compared to the control group. Altogether, these findings will provide valuable information for the discovery of potential probiotic candidates that inhibit CRC.
format article
author Byeong Seob Oh
Won Jung Choi
Ji-Sun Kim
Seoung Woo Ryu
Seung Yeob Yu
Jung-Sook Lee
Seung-Hwan Park
Se Won Kang
Jiyoung Lee
Won Yong Jung
Young-Min Kim
Jae-Ho Jeong
Ju Huck Lee
author_facet Byeong Seob Oh
Won Jung Choi
Ji-Sun Kim
Seoung Woo Ryu
Seung Yeob Yu
Jung-Sook Lee
Seung-Hwan Park
Se Won Kang
Jiyoung Lee
Won Yong Jung
Young-Min Kim
Jae-Ho Jeong
Ju Huck Lee
author_sort Byeong Seob Oh
title Cell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity
title_short Cell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity
title_full Cell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity
title_fullStr Cell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity
title_full_unstemmed Cell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity
title_sort cell-free supernatant of odoribacter splanchnicus isolated from human feces exhibits anti-colorectal cancer activity
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/a68b317525c24e1ab6618b04593705a3
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