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Functional characterisation of gut microbiota and metabolism in Type 2 diabetes indicates that Clostridiales and Enterococcus could play a key role in the disease

View ORCID ProfileMarina Mora-Ortiz, Alain Oregioni, View ORCID ProfileSandrine P. Claus
doi: https://doi.org/10.1101/836114
Marina Mora-Ortiz
1Department of Food and Nutritional Sciences, The University of Reading, Whiteknights campus, P.O. Box 226, Reading RG6 6AP, U.K.
2Department of Twin Research, Kings’ College London, St Thomas’ Hospital Campus, Westminster Bridge Road, London, SE1 7EW, U.K.
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  • ORCID record for Marina Mora-Ortiz
  • For correspondence: marina.mora_ortiz@kcl.ac.uk s.p.claus@reading.ac.uk
Alain Oregioni
3MRC Biomedical NMR Centre, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
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Sandrine P. Claus
1Department of Food and Nutritional Sciences, The University of Reading, Whiteknights campus, P.O. Box 226, Reading RG6 6AP, U.K.
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  • For correspondence: marina.mora_ortiz@kcl.ac.uk s.p.claus@reading.ac.uk
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Abstract

There is growing evidence indicating that gut microbiota contributes to the development of metabolic syndrome and Type 2 Diabetes (T2D). The most widely-used model for T2D research is the leptin deficient db/db mouse model. Yet, a characterisation of the gut microbial composition in this model in relationship with the metabolism is lacking. The objectives of this study were to identify metabolomics and microbial modulations associated with T2D in the db/db mouse model. The majority of microbial changes observed included an increase of Enterobacteriaceae and a decrease of Clostridiales in diabetics. The metabolomics interrogation of caecum indicated a lower proteolytic activity in diabetics, who also showed higher Short-Chain Fatty Acid (SCFA) levels. In the case of faeces, the model identified 9 metabolites, the main ones were acetate, butyrate and Branched Chain Amino Acids (BCAAs). Finally, liver was the organ with more metabolic links with gut-microbiota followed by the Gut-Brain Axis (GBA). In conclusion, the interaction between Clostridiales and Enterococcus with caecal metabolism could play a key role in the onset and development of diabetes. Further studies should investigate whether the role of these bacteria is causal or co-occurring.

  • Abbreviations

    BA
    Bile Acids
    BCAA
    Branched-Chain Amino Acids
    db/db mice
    mice: BKS.Cg-Dock7<m> +/+ Lepr<db>/ J mice
    NMR
    Nuclear Magnetic Resonance;
    TMA
    trimethylamine;
    TMAO
    trimethylamine-N-oxide;
    T2D
    Type Two Diabetes;
    O-PLS
    Orthogonal Projections to Latent Structures;
    SCFA
    Short-Chain Fatty Acids.
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    Posted November 09, 2019.
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    Functional characterisation of gut microbiota and metabolism in Type 2 diabetes indicates that Clostridiales and Enterococcus could play a key role in the disease
    Marina Mora-Ortiz, Alain Oregioni, Sandrine P. Claus
    bioRxiv 836114; doi: https://doi.org/10.1101/836114
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    Functional characterisation of gut microbiota and metabolism in Type 2 diabetes indicates that Clostridiales and Enterococcus could play a key role in the disease
    Marina Mora-Ortiz, Alain Oregioni, Sandrine P. Claus
    bioRxiv 836114; doi: https://doi.org/10.1101/836114

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