Differential longitudinal establishment of human fecal bacterial communities in germ-free porcine and murine models

Nirosh D Aluthge,Phillip S Miller,Amanda E Ramer-Tait,Alison C Bartenslager,Thomas E Burkey,Wesley A Tom,Hatem Kittana,Kelly D Heath,Robert J Schmaltz,Samodha C Fernando,Craig Kreikemeier-Bower

doi:10.1038/s42003-020-01477-0

Abstract

The majority of microbiome studies focused on understanding mechanistic relationships between the host and the microbiota have used mice and other rodents as the model of choice. However, the domestic pig is a relevant model that is currently underutilized for human microbiome investigations. In this study, we performed a direct comparison of the engraftment of fecal bacterial communities from human donors between human microbiota-associated (HMA) piglet and mouse models under identical dietary conditions. Analysis of 16S rRNA genes using amplicon sequence variants (ASVs) revealed that with the exception of early microbiota from infants, the more mature microbiotas tested established better in the HMA piglets compared to HMA mice. Of interest was the greater transplantation success of members belonging to phylum Firmicutes in the HMA piglets compared to the HMA mice. Together, these results provide evidence for the HMA piglet model potentially being more broadly applicable for donors with more mature microbiotas while the HMA mouse model might be more relevant for developing microbiotas such as those of infants. This study also emphasizes the necessity to exercise caution in extrapolating findings from HMA animals to humans, since up to 28% of taxa from some donors failed to colonize either model.

Highlights

The majority of microbiome studies focused on understanding mechanistic relationships between the host and the microbiota have used mice and other rodents as the model of choice
To compare the establishment of human fecal bacterial communities in human microbiotaassociated (HMA) mice and piglets, we inoculated GF mice and piglets maintained in gnotobiotic isolators with fecal matter from four separate human donors
Our results demonstrate that a greater number of amplicon sequence variants (ASVs) belonging to the phylum Firmicutes, especially those of the families Lachnospiraceae, Ruminococcaceae, and Christensenellaceae, from the human donors established and persisted in the HMA piglets compared to the HMA mice

Summary

Introduction

The majority of microbiome studies focused on understanding mechanistic relationships between the host and the microbiota have used mice and other rodents as the model of choice. Of interest was the greater transplantation success of members belonging to phylum Firmicutes in the HMA piglets compared to the HMA mice Together, these results provide evidence for the HMA piglet model potentially being more broadly applicable for donors with more mature microbiotas while the HMA mouse model might be more relevant for developing microbiotas such as those of infants. By transplanting fecal microbiotas from the same human donors into GF piglets and mice and maintaining both species under identical dietary and similar environmental conditions, we were able to directly compare the ability of HMA porcine and murine models to harbor and maintain ‘human-like’ gut bacterial communities over time. Members of the phylum Firmicutes had greater success in colonizing the HMA piglets compared to the HMA mice These findings point to the usefulness of both of these animal models for human microbiome studies with the HMA porcine model potentially having a broader scope

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Conclusion