Multi-omics Comparative Analysis Reveals Multiple Layers of Host Signaling Pathway Regulation by the Gut Microbiota

ABSTRACT The bodies of mammals are hosts to vast microbial communities composed of trillions of bacteria from thousands of species, whose effects on health and development have begun to be appreciated only recently. In this investigation, an integrated analysis combining proteomics and transcriptomi...

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Autores principales:	Nathan P. Manes, Natalia Shulzhenko, Arthur G. Nuccio, Sara Azeem, Andrey Morgun, Aleksandra Nita-Lazar
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	cell signaling host-microbiome interaction microbiota multi-omics proteomics systems biology Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9b792b17d6eb4b428219d2b05e5e4075
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spelling	oai:doaj.org-article:9b792b17d6eb4b428219d2b05e5e40752021-12-02T19:47:35ZMulti-omics Comparative Analysis Reveals Multiple Layers of Host Signaling Pathway Regulation by the Gut Microbiota10.1128/mSystems.00107-172379-5077https://doaj.org/article/9b792b17d6eb4b428219d2b05e5e40752017-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00107-17https://doaj.org/toc/2379-5077ABSTRACT The bodies of mammals are hosts to vast microbial communities composed of trillions of bacteria from thousands of species, whose effects on health and development have begun to be appreciated only recently. In this investigation, an integrated analysis combining proteomics and transcriptomics was used to quantitatively compare the terminal ilia from conventional and germfree mice. Female and male mice responded similarly to the microbiota, but C57BL/10A mice responded more strongly than BALB/c mice at both the transcriptome and proteome levels. The microbiota primarily caused upregulation of immunological pathways and downregulation of metabolic pathways in the conventional mice. Many of the affected pathways were altered only at either the transcriptome or proteome level. Of the pathways that were affected at both levels, most were affected concordantly. The discordant pathways were not principally involved in the immune system but instead were related to metabolism, oxidative phosphorylation, protein translation, transport, and turnover. To broaden the discovery of affected host pathways, a meta-analysis was performed using intestinal transcriptomics data from previously published studies of germfree versus conventional mice with diverse microbiota populations. Similar transcript-level responses to the microbiota were found, and many additional affected host pathways were discovered. IMPORTANCE Multiple host pathways were affected by its adaptation to the microbiota. We have found significant transcriptome-proteome discordance caused by the microbiota. This discovery leads to the definite conclusion that transcript-level analysis is not sufficient to predict protein levels and their influence on the function of many specific cellular pathways, so only analysis of combinations of the quantitative data determined at different levels will lead to a complete understanding of the complex relationships between the host and the microbiota. Therefore, our results demonstrate the importance of using an integrative approach to study host-microbiota interaction at the molecular level.Nathan P. ManesNatalia ShulzhenkoArthur G. NuccioSara AzeemAndrey MorgunAleksandra Nita-LazarAmerican Society for Microbiologyarticlecell signalinghost-microbiome interactionmicrobiotamulti-omicsproteomicssystems biologyMicrobiologyQR1-502ENmSystems, Vol 2, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell signaling host-microbiome interaction microbiota multi-omics proteomics systems biology Microbiology QR1-502
spellingShingle	cell signaling host-microbiome interaction microbiota multi-omics proteomics systems biology Microbiology QR1-502 Nathan P. Manes Natalia Shulzhenko Arthur G. Nuccio Sara Azeem Andrey Morgun Aleksandra Nita-Lazar Multi-omics Comparative Analysis Reveals Multiple Layers of Host Signaling Pathway Regulation by the Gut Microbiota
description	ABSTRACT The bodies of mammals are hosts to vast microbial communities composed of trillions of bacteria from thousands of species, whose effects on health and development have begun to be appreciated only recently. In this investigation, an integrated analysis combining proteomics and transcriptomics was used to quantitatively compare the terminal ilia from conventional and germfree mice. Female and male mice responded similarly to the microbiota, but C57BL/10A mice responded more strongly than BALB/c mice at both the transcriptome and proteome levels. The microbiota primarily caused upregulation of immunological pathways and downregulation of metabolic pathways in the conventional mice. Many of the affected pathways were altered only at either the transcriptome or proteome level. Of the pathways that were affected at both levels, most were affected concordantly. The discordant pathways were not principally involved in the immune system but instead were related to metabolism, oxidative phosphorylation, protein translation, transport, and turnover. To broaden the discovery of affected host pathways, a meta-analysis was performed using intestinal transcriptomics data from previously published studies of germfree versus conventional mice with diverse microbiota populations. Similar transcript-level responses to the microbiota were found, and many additional affected host pathways were discovered. IMPORTANCE Multiple host pathways were affected by its adaptation to the microbiota. We have found significant transcriptome-proteome discordance caused by the microbiota. This discovery leads to the definite conclusion that transcript-level analysis is not sufficient to predict protein levels and their influence on the function of many specific cellular pathways, so only analysis of combinations of the quantitative data determined at different levels will lead to a complete understanding of the complex relationships between the host and the microbiota. Therefore, our results demonstrate the importance of using an integrative approach to study host-microbiota interaction at the molecular level.
format	article
author	Nathan P. Manes Natalia Shulzhenko Arthur G. Nuccio Sara Azeem Andrey Morgun Aleksandra Nita-Lazar
author_facet	Nathan P. Manes Natalia Shulzhenko Arthur G. Nuccio Sara Azeem Andrey Morgun Aleksandra Nita-Lazar
author_sort	Nathan P. Manes
title	Multi-omics Comparative Analysis Reveals Multiple Layers of Host Signaling Pathway Regulation by the Gut Microbiota
title_short	Multi-omics Comparative Analysis Reveals Multiple Layers of Host Signaling Pathway Regulation by the Gut Microbiota
title_full	Multi-omics Comparative Analysis Reveals Multiple Layers of Host Signaling Pathway Regulation by the Gut Microbiota
title_fullStr	Multi-omics Comparative Analysis Reveals Multiple Layers of Host Signaling Pathway Regulation by the Gut Microbiota
title_full_unstemmed	Multi-omics Comparative Analysis Reveals Multiple Layers of Host Signaling Pathway Regulation by the Gut Microbiota
title_sort	multi-omics comparative analysis reveals multiple layers of host signaling pathway regulation by the gut microbiota
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/9b792b17d6eb4b428219d2b05e5e4075
work_keys_str_mv	AT nathanpmanes multiomicscomparativeanalysisrevealsmultiplelayersofhostsignalingpathwayregulationbythegutmicrobiota AT nataliashulzhenko multiomicscomparativeanalysisrevealsmultiplelayersofhostsignalingpathwayregulationbythegutmicrobiota AT arthurgnuccio multiomicscomparativeanalysisrevealsmultiplelayersofhostsignalingpathwayregulationbythegutmicrobiota AT saraazeem multiomicscomparativeanalysisrevealsmultiplelayersofhostsignalingpathwayregulationbythegutmicrobiota AT andreymorgun multiomicscomparativeanalysisrevealsmultiplelayersofhostsignalingpathwayregulationbythegutmicrobiota AT aleksandranitalazar multiomicscomparativeanalysisrevealsmultiplelayersofhostsignalingpathwayregulationbythegutmicrobiota
_version_	1718375978528407552

Multi-omics Comparative Analysis Reveals Multiple Layers of Host Signaling Pathway Regulation by the Gut Microbiota

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