Donor Microbiota Composition and Housing Affect Recapitulation of Obese Phenotypes in a Human Microbiota-Associated Murine Model

Thomas Kaiser, Harika Nalluri, Zhigang Zhu, Christopher Staley

Research output: Contribution to journalArticlepeer-review

Abstract

Human microbiota-associated (HMA) mouse models offer a valuable approach to study the role of intestinal microbiota in the development of obesity. In this study, we used an HMA model to evaluate whether engraftment of human obese or lean microbiota, from each of three donors, could recapitulate host phenotypes under conventional and specific-pathogen-free housing. Microbiota engraftment was correlated with donor relative abundances of the class Bacteroidia (Spearman’s ρ = 0.73, P ≤ 0.001), and one obese donor resulted in significant weight gain (P ≤ 0.003) and compromised insulin sensitivity under conventional housing. SPF housing partially blunted phenotypic response. Results of this study indicate that our HMA model partially recapitulates obese phenotypes under conventional housing and highlights a need to consider donor-specific effects as well as housing conditions when studying the role of the microbiota in obesity.

Original languageEnglish (US)
Article number614218
JournalFrontiers in Cellular and Infection Microbiology
Volume11
DOIs
StatePublished - Feb 22 2021

Bibliographical note

Funding Information:
Sequence data processing and analysis were done using the resources of the Minnesota Supercomputing Institute. We would like to thank Shannon Jannatpour and Marcia Brott with the Surgical Clinical Trials Office and Drs. Alexander Khoruts and Matthew Hamilton as well as Carolyn Graiziger with the Microbiota Therapeutics Program for assistance with sample collection. We also thank Meri DuRand for assistance with the mouse gavage.

Publisher Copyright:
© Copyright © 2021 Kaiser, Nalluri, Zhu and Staley.

Keywords

  • conventional housing
  • fecal microbiota transplantation
  • human microbiota-associated
  • mouse model
  • obesity
  • specific pathogen-free

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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