Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice

Although gut microbiota has been linked to cancer, little is known about the crosstalk between gut- and intratumoral-microbiomes. The goal of this study was to determine whether gut Akkermansia muciniphila (Akk) is involved in the regulation of intratumoral microbiome and metabolic contexture, leadi...

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Autores principales: Zhu, Zhuxian, Cai, Jixu, Hou, Weiwei, Xu, Ke, Wu, Xuxiao, Song, Yuanlin, Bai, Chunxue, Mo, Yin-Yuan, Zhang, Ziqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904296/
https://www.ncbi.nlm.nih.gov/pubmed/36740846
http://dx.doi.org/10.1080/19490976.2023.2166700
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author Zhu, Zhuxian
Cai, Jixu
Hou, Weiwei
Xu, Ke
Wu, Xuxiao
Song, Yuanlin
Bai, Chunxue
Mo, Yin-Yuan
Zhang, Ziqiang
author_facet Zhu, Zhuxian
Cai, Jixu
Hou, Weiwei
Xu, Ke
Wu, Xuxiao
Song, Yuanlin
Bai, Chunxue
Mo, Yin-Yuan
Zhang, Ziqiang
author_sort Zhu, Zhuxian
collection PubMed
description Although gut microbiota has been linked to cancer, little is known about the crosstalk between gut- and intratumoral-microbiomes. The goal of this study was to determine whether gut Akkermansia muciniphila (Akk) is involved in the regulation of intratumoral microbiome and metabolic contexture, leading to an anticancer effect on lung cancer. We evaluated the effects of gut endogenous or gavaged exogenous Akk on the tumorigenesis using the Lewis lung cancer mouse model. Feces, blood, and tumor tissue samples were collected for 16S rDNA sequencing. We then conducted spatially resolved metabolomics profiling to discover cancer metabolites in situ directly and to characterize the overall Akk-regulated metabolic features, followed by the correlation analysis of intratumoral bacteria with metabolic network. Our results showed that both endogenous and exogenous gavaged Akk significantly inhibited tumorigenesis. Moreover, we detected increased Akk abundance in blood circulation or tumor tissue by 16S rDNA sequencing in the Akk gavaged mice, compared with the control mice. Of great interest, gavaged Akk may migrate into tumor tissue and influence the composition of intratumoral microbiome. Spatially resolved metabolomics analysis revealed that the gut-derived Akk was able to regulate tumor metabolic pathways, from metabolites to enzymes. Finally, our study identified a significant correlation between the gut Akk-regulated intratumoral bacteria and metabolic network. Together, gut-derived Akk may migrate into blood circulation, and subsequently colonize into lung cancer tissue, which contributes to the suppression of tumorigenesis by influencing tumoral symbiotic microbiome and reprogramming tumoral metabolism, although more studies are needed.
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spelling pubmed-99042962023-02-08 Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice Zhu, Zhuxian Cai, Jixu Hou, Weiwei Xu, Ke Wu, Xuxiao Song, Yuanlin Bai, Chunxue Mo, Yin-Yuan Zhang, Ziqiang Gut Microbes Research Paper Although gut microbiota has been linked to cancer, little is known about the crosstalk between gut- and intratumoral-microbiomes. The goal of this study was to determine whether gut Akkermansia muciniphila (Akk) is involved in the regulation of intratumoral microbiome and metabolic contexture, leading to an anticancer effect on lung cancer. We evaluated the effects of gut endogenous or gavaged exogenous Akk on the tumorigenesis using the Lewis lung cancer mouse model. Feces, blood, and tumor tissue samples were collected for 16S rDNA sequencing. We then conducted spatially resolved metabolomics profiling to discover cancer metabolites in situ directly and to characterize the overall Akk-regulated metabolic features, followed by the correlation analysis of intratumoral bacteria with metabolic network. Our results showed that both endogenous and exogenous gavaged Akk significantly inhibited tumorigenesis. Moreover, we detected increased Akk abundance in blood circulation or tumor tissue by 16S rDNA sequencing in the Akk gavaged mice, compared with the control mice. Of great interest, gavaged Akk may migrate into tumor tissue and influence the composition of intratumoral microbiome. Spatially resolved metabolomics analysis revealed that the gut-derived Akk was able to regulate tumor metabolic pathways, from metabolites to enzymes. Finally, our study identified a significant correlation between the gut Akk-regulated intratumoral bacteria and metabolic network. Together, gut-derived Akk may migrate into blood circulation, and subsequently colonize into lung cancer tissue, which contributes to the suppression of tumorigenesis by influencing tumoral symbiotic microbiome and reprogramming tumoral metabolism, although more studies are needed. Taylor & Francis 2023-02-05 /pmc/articles/PMC9904296/ /pubmed/36740846 http://dx.doi.org/10.1080/19490976.2023.2166700 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Zhu, Zhuxian
Cai, Jixu
Hou, Weiwei
Xu, Ke
Wu, Xuxiao
Song, Yuanlin
Bai, Chunxue
Mo, Yin-Yuan
Zhang, Ziqiang
Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice
title Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice
title_full Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice
title_fullStr Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice
title_full_unstemmed Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice
title_short Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice
title_sort microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904296/
https://www.ncbi.nlm.nih.gov/pubmed/36740846
http://dx.doi.org/10.1080/19490976.2023.2166700
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