Abstract

The intestinal microbiota and its functions are intricately interwoven with host physiology. Colonizing rodents with donor microbiota provides insights into host-microbiota interactions characterization and the understanding of disease physiopathology. However, a better assessment of inoculation methods and recipient mouse models is needed. Here, we compare the engraftment at short and long term of genetically obese mice microbiota in germ-free (GF) mice and juvenile and adult specific pathogen free (SPF) mice. We also tested the effects of initial microbiota depletion before microbiota transfer. In the present work, donor microbiota engraftment was better in juvenile SPF mice than in adult SPF mice. In juvenile mice, initial microbiota depletion using laxatives or antibiotics improved donor microbiota engraftment 9 weeks but not 3 weeks after microbiota transfer. Microbiota-depleted juvenile mice performed better than GF mice 3 weeks after the microbiota transfer. However, 9 weeks after transfer, colonized GF mice microbiota had the lowest Unifrac distance to the donor microbiota. Colonized GF mice were also characterized by a chronic alteration in intestinal absorptive function. With these collective results, we show that the use of juvenile mice subjected to initial microbiota depletion constitutes a valid alternative to GF mice in microbiota transfer studies.

Highlights

  • The microorganisms that inhabit the gastrointestinal tract of mammals, termed the gut microbiota, are critical in host physiology regulation by influencing metabolism (Bäckhed et al, 2004), immunity/inflammation (Cebra, 1999), aging (Smith et al, 2017), and behavior (Leclercq et al, 2017)

  • We depleted the intestinal microbiota of 3-week old specific pathogen free (SPF) mice with either efficient bowel cleansing with polyethylene glycol (PEG) or 7 days antibiotics treatment followed by bowel cleansing with PEG

  • We tested the effect of recipient model choice in the specific context of Lepob to wild-type mice gut microbiota transfer, our results suggest that simple gavage administration of mouse donor microbiota effectively reshapes intestinal microbiota in SPF recipients

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Summary

Introduction

The microorganisms that inhabit the gastrointestinal tract of mammals, termed the gut microbiota, are critical in host physiology regulation by influencing metabolism (Bäckhed et al, 2004), immunity/inflammation (Cebra, 1999), aging (Smith et al, 2017), and behavior (Leclercq et al, 2017). Co-housing cannot be performed for microbiota transfer from human to mouse (Llopis et al, 2016) or when donor and recipient mice are fed different diets (Anhê et al, 2018). The frequency and the length of inoculum administration range from a single administration to twice a week for several weeks (Hintze et al, 2014; Ferrere et al, 2017; Wrzosek et al, 2018) These experimental strategies have more or less been documented regarding the efficacy of microbiota transfer, which can be defined as (i) establishment of a high proportion of inoculum’s bacterial taxa in recipients, (ii) relative abundances of bacterial taxa in the recipients as similar as possible to that of the inoculum and (iii) the removal of a high proportion of endogenous bacterial taxa in case of non-GF recipients

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