Objective Faecal microbiota transplantation (FMT) in germ-free (GF) mice is a common approach to study the causal role of the gut microbiota in metabolic diseases. Lack of consideration of housing conditions post-FMT may contribute to study heterogeneity. We compared the impact of two housing strategies on the metabolic outcomes of GF mice colonised by gut microbiota from mice treated with a known gut modulator (cranberry proanthocyanidins (PAC)) or vehicle.
Design High-fat high-sucrose diet-fed GF mice underwent FMT-PAC colonisation in sterile individual positive flow ventilated cages under rigorous housing conditions and then maintained for 8 weeks either in the gnotobiotic-axenic sector or in the specific pathogen free (SPF) sector of the same animal facility.
Results Unexpectedly, 8 weeks after colonisation, we observed opposing liver phenotypes dependent on the housing environment of mice. Mice housed in the GF sector receiving the PAC gut microbiota showed a significant decrease in liver weight and hepatic triglyceride accumulation compared with control group. Conversely, exacerbated liver steatosis was observed in the FMT-PAC mice housed in the SPF sector. These phenotypic differences were associated with housing-specific profiles of colonising bacterial in the gut and of faecal metabolites.
Conclusion These results suggest that the housing environment in which gnotobiotic mice are maintained post-FMT strongly influences gut microbiota composition and function and can lead to distinctive phenotypes in recipient mice. Better standardisation of FMT experiments is needed to ensure reproducible and translatable results.
- intestinal bacteria
- fatty liver
Data availability statement
Data are available on reasonable request. The data that support the findings of this study are available from the corresponding author, AM, on request.
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LD and BSC are joint first authors.
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Contributors LD, BS-YC, GP and AM conceived the study and wrote the manuscript with inputs from all co-authors. LD and BS-YC conducted animal studies and related measurements with the help from AO, PLM and NS. TVV performed 16S sequencing analyses. A-LA performed untargeted metabolomic analyses. YD prepared the PAC extract. EL performed antioxidant enzymes analysis. FFA contributed to bioinformatic analyses and gave feedback over the duration of the study. ML aided in interpreting the results and supervised parts of the study. GP, VPH and AM supervised the study. LD, BS-YC and AM are guarantors and responsible for the integrity of the work as a whole. All authors reviewed the manuscript.
Funding This work was funded by the Weston Garfield Foundation and by a Foundation grant (FDN-143247) from the Canadian Institutes for Health Research (CIHR) to AM. AM is the recipient of a CIHR/Pfizer research chair in the pathogenesis of insulin resistance and cardiovascular diseases and J.A.-DeSève foundation. LD is funded by a doctoral scholarship from Fonds de recherche du Québec. BS-YC is funded by doctoral scholarships from the Sentinel North programme at Laval University (Canada First Research Excellence Fund) and from the Natural Sciences and Engineering Research Council of Canada (NSERC).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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