1. Microbiology and Infectious Disease
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The East Asian gut microbiome is distinct from colocalized white subjects and connected to metabolic health

  1. Qi Yan Ang
  2. Diana L Alba
  3. Vaibhav Upadhyay
  4. Jordan E Bisanz
  5. Jingwei Cai
  6. Ho Lim Lee
  7. Eliseo Barajas
  8. Grace Wei
  9. Cecilia Noecker
  10. Andrew D Patterson
  11. Suneil K Koliwad  Is a corresponding author
  12. Peter J Turnbaugh  Is a corresponding author
  1. University of California, San Francisco, United States
  2. Pennsylvania State University, United States
Research Article
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Cite this article as: eLife 2021;10:e70349 doi: 10.7554/eLife.70349

Abstract

East Asians experience worse metabolic health outcomes compared to other ethnic groups at lower body mass indices; however, the potential role of the gut microbiota in contributing to these health disparities remains unknown. We conducted a multi-omic study of 46 lean and obese East Asian and White participants living in the San Francisco Bay Area, revealing marked differences between ethnic groups in bacterial richness and community structure. White individuals were enriched for the mucin-degrading Akkermansia muciniphila. East Asian subjects had increased levels of multiple bacterial phyla, fermentative pathways detected by metagenomics, and the short-chain fatty acid end-products acetate, propionate, and isobutyrate. Differences in the gut microbiota between the East Asian and White subjects could not be explained by dietary intake, were more pronounced in lean individuals, and were associated with current geographical location. Microbiome transplantations into germ-free mice demonstrated stable diet- and host genotype-independent differences between the gut microbiotas of East Asian and White individuals that differentially impact host body composition. Taken together, our findings add to the growing body of literature describing variation between ethnicities and provide a starting point for defining the mechanisms through which the microbiome may shape disparate health outcomes in East Asians.

Data availability

All 16S-seq and metagenomic sequencing data generated in the preparation of this manuscript have been deposited in NCBI's Sequence Read Archive under accession number PRJNA665061. Metabolomics results and metadata are available within this manuscript (Tables S2, S4, S5, and S9). Code for our manuscript will be uploaded to GitHub (https://github.com/turnbaughlab/2021_IDEO).

The following data sets were generated

Article and author information

Author details

  1. Qi Yan Ang

    University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  2. Diana L Alba

    University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  3. Vaibhav Upadhyay

    University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  4. Jordan E Bisanz

    University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8649-1706
  5. Jingwei Cai

    Pennsylvania State University, College Park, United States
    Competing interests
    No competing interests declared.
  6. Ho Lim Lee

    University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  7. Eliseo Barajas

    University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  8. Grace Wei

    University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  9. Cecilia Noecker

    University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  10. Andrew D Patterson

    Pennsylvania State University, College Park, United States
    Competing interests
    No competing interests declared.
  11. Suneil K Koliwad

    University of California, San Francisco, San Francisco, United States
    For correspondence
    Suneil.Koliwad@ucsf.edu
    Competing interests
    No competing interests declared.
  12. Peter J Turnbaugh

    University of California, San Francisco, San Francisco, United States
    For correspondence
    Peter.Turnbaugh@ucsf.edu
    Competing interests
    Peter J Turnbaugh, is on the scientific advisory board for Kaleido, Pendulum, Seres, and SNIPRbiome; there is no direct overlap between the current study and these consulting duties.Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0888-2875

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK114034)

  • Peter J Turnbaugh

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK11230401)

  • Suneil K Koliwad

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Protocols for all experiments involving mice were approved by the University of California, San Francisco Institutional Animal Care and Use Committee, and performed accordingly (UCSF IACUC numbers AN183950 and AN184143).

Human subjects: Informed consent was provided for all subjects participating in the study, which was approved by the UCSF Institutional Review Board.

Reviewing Editor

  1. Andrew J MacPherson, University of Bern, Switzerland

Publication history

  1. Received: May 14, 2021
  2. Accepted: October 6, 2021
  3. Accepted Manuscript published: October 7, 2021 (version 1)
  4. Accepted Manuscript updated: October 8, 2021 (version 2)

Copyright

© 2021, Ang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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    2. Microbiology and Infectious Disease
    Nguyen Thi Thuy Ngan et al.
    Research Article Updated

    Background:

    Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anticancer agent tamoxifen has synergistic anti-cryptococcal activity with amphotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential.

    Methods:

    Open label randomized controlled trial. Participants received standard care – amphotericin combined with fluconazole for the first 2 weeks – or standard care plus tamoxifen 300 mg/day. The primary end point was Early Fungicidal Activity (EFA) – the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration https://clinicaltrials.gov/ct2/show/NCT03112031.

    Results:

    Fifty patients were enrolled (median age 34 years, 35 male). Tamoxifen had no effect on EFA (−0.48log10 colony-forming units/mL/CSF control arm versus −0.49 tamoxifen arm, difference −0.005log10CFU/ml/day, 95% CI: −0.16, 0.15, p=0.95). Tamoxifen caused QTc prolongation.

    Conclusions:

    High-dose tamoxifen does not increase the clearance rate of Cryptococcus from CSF. Novel, affordable therapies are needed.

    Funding:

    The trial was funded through the Wellcome Trust Asia Programme Vietnam Core Grant 106680 and a Wellcome Trust Intermediate Fellowship to JND grant number WT097147MA.

    1. Genetics and Genomics
    2. Microbiology and Infectious Disease
    Thomas Hackl et al.
    Research Article

    Virophages can parasitize giant DNA viruses and may provide adaptive anti-giant virus defense in unicellular eukaryotes. Under laboratory conditions, the virophage mavirus integrates into the nuclear genome of the marine flagellate Cafeteria burkhardae and reactivates upon superinfection with the giant virus CroV. In natural systems, however, the prevalence and diversity of host-virophage associations has not been systematically explored. Here, we report dozens of integrated virophages in four globally sampled C. burkhardae strains that constitute up to 2% of their host genomes. These endogenous mavirus-like elements (EMALEs) separated into eight types based on GC-content, nucleotide similarity, and coding potential and carried diverse promoter motifs implicating interactions with different giant viruses. Between host strains, some EMALE insertion loci were conserved indicating ancient integration events, whereas the majority of insertion sites were unique to a given host strain suggesting that EMALEs are active and mobile. Furthermore, we uncovered a unique association between EMALEs and a group of tyrosine recombinase retrotransposons, revealing yet another layer of parasitism in this nested microbial system. Our findings show that virophages are widespread and dynamic in wild Cafeteria populations, supporting their potential role in antiviral defense in protists.