Laboratory Animals - June Issue - 244

Special Issue: Microbiota

Humanizing the gut microbiota of mice:
Opportunities and challenges

Laboratory Animals
2019, Vol. 53(3) 244-251
! The Author(s) 2018
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DOI: 10.1177/0023677218787554
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Randi Lundberg

Abstract
Mouse colonized with human fecal microbiota is an interesting model concept with pros and cons like any
other model system. The concept provides an ecologically relevant context to study food component and drug
metabolism, and is an invaluable tool for phenotype transfer studies to prove the role of the gut microbiota in
health and disease. The major drawbacks are the difficulties with transferring certain components of the
human microbiota to the recipient mice, and immunological abnormalities observed in these mice. There
seem to be unexplored opportunities for trying to reduce these limitations, but careful evaluation of pros, cons
and possible alternatives is still necessary.
Keywords
animal model, comparative medicine, gut microbiota, humanization, immunology, organisms and models,
physiology
Date received: 1 April 2018; accepted: 15 June 2018

Introduction
There is a need for in vivo models able to capture the
complexity of the human microbiome in conjunction
with a biologically relevant host. For several reasons,
mice are among the most popular animal models in
biomedical research and they are the primary focus of
this review. Mice can, with relative ease, be derived to a
germ-free (GF) state characterized by the absence of
microorganisms, a valuable concept for microbiome
researchers. Despite some overlap, there are profound
differences between which microorganisms primarily
colonize laboratory mice versus humans, which may
make mice with a mouse-specific gut microbiota
(GM) less translationally relevant. Humanizing the
GM of GF rodents is, therefore, a frequently used
tool to enhance translation to humans.

studies of function and host effects of specific organisms
and their inter-organism synergies and interactions.1,2,3
The holistic approach involves transferring a complex
GM from human patients or healthy donors to germfree (GF) hosts. Mechanistic insights are more difficult
to obtain from studies utilizing the holistic approach,
whereas it is useful for hypothesis-generation and for
proving the causative role of GM in various conditions
by phenotype transfer from donor to recipients.
An alternative to using GF recipients is to
diminish the existing GM with broad-spectrum antibiotics, an approach discussed elsewhere.4 For the
reductionist approaches, GF is the only meaningful
solution because it allows for precise control of
what organisms are present. Holistic colonization
with a complex GM may utilize a host with its resident
GM depleted by antibiotics,5 as long as it is realized
that the colonization success can vary according to the

The humanized gut microbiota concept
The concept of humanizing the gut microbiota (GM) of
mice can take one of two overall paths: a reductionist or
a holistic approach. The reductionist approach comprises
mono- and multicolonizations with defined organisms
and is based on control of which microorganisms are
present in the host. This allows for precise mechanistic

Internal Research and Development, Taconic Biosciences, Lille
Skensved, Denmark
Corresponding author:
Randi Lundberg, Chr. Hansen, Bøge Alle
´ 10-12, 2970 Hørsholm,
Denmark.
Email: lundberg.randi@gmail.com


https://uk.sagepub.com/en-gb/journals-permissions https://uk.sagepub.com/en-gb/journals-permissions https://www.doi.org/10.1177/0023677218787554 http://journals.sagepub.com/home/lan http://www.orcid.org/0000-0002-6646-6036

Laboratory Animals - June Issue

Table of Contents for the Digital Edition of Laboratory Animals - June Issue

Contents
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