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Diet Induces Reproducible Alterations in the Mouse and Human Gut Microbiome

27 Pages Posted: 7 Feb 2019 Sneak Peek Status: Published

See all articles by Jordan E. Bisanz

Jordan E. Bisanz

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Vaibhav Upadhyay

University of California, San Francisco (UCSF) - Department of Internal Medicine

Jessie A. Turnbaugh

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Kimberly Ly

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Peter Turnbaugh

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology; Chan Zuckerberg Biohub

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Abstract

The degree to which diet reproducibly alters the human and mouse gut microbiota remains unclear. Here, we focus on the consumption of a high-fat diet (HFD), one of the most frequently studied dietary interventions in mice. We employed a subject-level meta-analysis framework for unbiased collection and analysis of publicly available 16S rRNA gene and metagenomic sequencing data from studies examining HFD in rodent models. In total, we re-analyzed 27 studies, 1101 samples, and 106 million reads mapping to 16S rRNA gene sequences. We report reproducible changes in gut microbial community structure both within and between studies, including a signi cant increase in the Firmicutes phylum and decrease in the Bacteroidetes phylum; however, reduced alpha diversity is not a consistent feature of HFD. Finer taxonomic analysis revealed that the strongest signal of HFD on microbiota species composition is Lactococcus spp., which we demonstrate is a common dietary contaminant through the molecular testing of dietary ingredients, culturing, microscopy, and germfree mouse experiments. After in silico removal of Lactococcus spp., we employed machine learning to de ne a unique operational taxonomic unit (OTU)-based signature capable of predicting the dietary intake of mice and demonstrate that phylogenetic and gene-family transformations of this model are capable of accurately predicting human samples in controlled feeding settings (area under the receiver operator curve = 0.75 and 0.88 respectively). Together, these results demonstrate the utility of microbiome meta-analyses in identifying robust bacterial signals for mechanistic studies and creates a framework for the routine meta-analysis of microbiome studies in preclinical models.

Keywords: Microbiome, Meta-analysis, High-fat diet, Murine

Suggested Citation

Bisanz, Jordan E. and Upadhyay, Vaibhav and Turnbaugh, Jessie A. and Ly, Kimberly and Turnbaugh, Peter, Diet Induces Reproducible Alterations in the Mouse and Human Gut Microbiome (February 7, 2019). Available at SSRN: https://ssrn.com/abstract=3330558 or http://dx.doi.org/10.2139/ssrn.3330558
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Jordan E. Bisanz

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

San Francisco, CA 94143
United States

Vaibhav Upadhyay

University of California, San Francisco (UCSF) - Department of Internal Medicine

San Francisco, CA 94143
United States

Jessie A. Turnbaugh

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

San Francisco, CA 94143
United States

Kimberly Ly

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

San Francisco, CA 94143
United States

Peter Turnbaugh (Contact Author)

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology ( email )

San Francisco, CA 94143
United States

Chan Zuckerberg Biohub ( email )

499 Illinois Street
San Francisco, CA 94158
United States

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