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Effect of gut microbiota on host whole metabolome

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Abstract

Introduction

Recent advances in microbiome research have revealed the diverse participation of gut microbiota in a number of diseases. Bacteria-specific endogenous small molecules are produced in the gut, are transported throughout the whole body by circulation, and play key roles in disease establishment. However, the factors and mechanisms underlying these microbial influences largely remain unknown.

Objectives

The purpose of this study was to use metabolomics to better understand the influence of microbiota on host physiology.

Methods

Germ-free mice (GF) were orally administered with the feces of specific pathogen-free (SPF) mice and were maintained in a vinyl isolator for 4 weeks for establishing the so-called ExGF mice. Comparative metabolomics was performed on luminal contents, feces, urine, plasma, and tissues of GF and ExGF mice.

Results

The metabolomics profile of 1716 compounds showed marked difference between GF and ExGF for each matrix. Intestinal differences clearly showed the contribution of microbiota to host digestive activities. In addition, colonic metabolomics revealed the efficient conversion of primary to secondary metabolites by microbiota. Furthermore, metabolomics of tissues and excrements demonstrated the effect of microbiota on the accumulation of metabolites in tissues and during excretion. These effects included known bacterial effects (such as bile acids and amino acids) as well as novel ones, including a drastic decrease of sphingolipids in the host.

Conclusion

The diverse effects of microbiota on different sites of the host metabolome were revealed and novel influences on host physiology were demonstrated. These findings should contribute to a deeper understanding of the influence of gut microbiota on disease states and aid in the development of effective intervention strategies.

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Abbreviations

5HL:

5-Hydroxylysine

3MH:

3-Methylhistidine

BCAA:

Branched-chain amino acid

FA:

Formic acid

FFA:

Free fatty acid

GF:

Germ-free

IACUC:

Institutional animal care and use committees

MS:

Mass spectrometry

NASH:

Non-alcoholic steatohepatitis

NCI:

National Cancer Institute

NGS:

Next generation sequencer

OTU:

Operational taxonomic unit

QIIME:

Quantitative insights into microbial ecology

SPF:

Specific pathogen-free

UPLC:

Ultra-performance liquid chromatography

HESI-II:

Heated electrospray ionization-II

PFPA:

Perfluoropentanoic acid

HILIC:

Hydrophilic interaction chromatography

FDR:

False discovery rate

SPF:

Specific pathogen-free

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Authors and Affiliations

  1. Integrated Technology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan

    Takeo Moriya, Yoshinori Satomi, Shumpei Murata, Hiroshi Sawada & Hiroyuki Kobayashi

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  1. Takeo Moriya
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  2. Yoshinori Satomi
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  3. Shumpei Murata
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  4. Hiroshi Sawada
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Correspondence to Hiroyuki Kobayashi.

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‘Takeo Moriya, Yoshinori Satomi, Shumpei Murata, Hiroshi Sawada, and Hiroyuki Kobayashi’ declare that they have no conflict of interest.

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All animal studies were performed in accordance with the Institute of Laboratory Animal Resources guidelines and approved by the Institutional Animal Care and Use Committees (IACUC) of Sankyo-labo Service Co.

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Moriya, T., Satomi, Y., Murata, S. et al. Effect of gut microbiota on host whole metabolome. Metabolomics 13, 101 (2017). https://doi.org/10.1007/s11306-017-1240-9

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