Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design

Abstract

Targeted manipulation of the gut flora is increasingly being recognized as a means to improve human health. Yet, the temporal dynamics and intra- and interindividual heterogeneity of the microbiome represent experimental limitations, especially in human cross-sectional studies. Therefore, rodent models represent an invaluable tool to study the host–microbiota interface. Progress in technical and computational tools to investigate the composition and function of the microbiome has opened a new era of research and we gradually begin to understand the parameters that influence variation of host-associated microbial communities. To isolate true effects from confounding factors, it is essential to include such parameters in model intervention studies. Also, explicit journal instructions to include essential information on animal experiments are mandatory. The purpose of this review is to summarize the factors that influence microbiota composition in mice and to provide guidelines to improve the reproducibility of animal experiments.

The Mouse Intestinal Bacterial Collection (miBC) provides host-specific insight into cultured diversity and functional potential of the gut microbiota

“…In contrast, the minimal bacteriome presented here contains strains that originate from the mouse intestine, is publicly available, was selected on the basis of comprehensive sequence-based approaches, and was overall characterized by a higher coverage of mouse faecal metagenomes. Hence, it represents important progress towards the standardization of mouse models, as emphasized by others 35,38 . However, additional work is required for establishment of the consortium in vivo.…”

Analysis of factors contributing to variation in the C57BL/6J fecal microbiota across German animal facilities

“…chow supply, mouse strains, hygiene plan, etc.) lead to differences among facilities (Martiny et al, 2011), which may contribute to the lack of consistency in microbiome studies involving many mouse models (Laukens et al, 2016). However, still little is known regarding the relative impact of the many potential factors influencing variation in the lab mouse fecal microbiota over a broad scale.…”

Antibiotic treatment and stewardship in the era of microbiota-oriented diagnostics

“…In a sense, our microbiota even display antibiotic activities themselves. Therefore, one could claim a healthy diverse microbiome defines an individual's health status [6]. Better understanding of the changes in this diversity and shifts in microbiota composition by antibiotic usage will protect or even improve our health status [7].…”