A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes

Abstract

25 26 Mus musculus is the classic mammalian model for biomedical research. Despite global efforts 27 in standardizing breeding and experimental procedures, the undefined nature and inter-28 individual diversity of laboratory mouse microbiota remains a limitation. In an attempt to 29 standardize preclinical studies, we have developed a simplified mouse microbiota composed 30 of 15 strains from 7 of the 20 most prevalent bacterial families representative of the fecal 31 microbiota found in specific opportunistic-and pathogen-free (SOPF) C57BL/6J animals and 32 derived a standardized gnotobiotic mouse model called GM15. GM15 recapitulates extensively 33 the functionalities found in C57BL/6J SOPF microbiota metagenome and GM15 animals are 34 phenotypically similar to SOPF. They even perform better in a model of post-weaning 35 malnutrition. The GM15 model ensures an increased reproducibility and robustness of 36 preclinical studies by limiting the confounding effect of microbiota composition fluctuation and 37 offers new possibilities for research focusing on how the microbiota shapes host physiology in 38 health and diseases. 39 40

Enhanced cultured diversity of the mouse gut microbiota enables custom-made synthetic communities

“…There are only a few examples of synthetic communities (SYNs) from the mouse intestine that have been established and used since the 1960s. [31][32][33] Such models can be implemented in two manners: (I) as reference communities to perform gnotobiotic studies under controlled and reproducible conditions; 32,38 or (II) as modular systems to test the effects of specific strains added to the community. 34,37 By amending the original OMM12 model via the addition of phylogenetically and functionally complementary strains and by making the corresponding strains mixtures and all single miBC strains available, the work presented here facilitates both types of models aforementioned.…”

“…A few low-diversity mouse microbiota used as reference gut communities have been published to date, [31][32][33] including the Oligo-Mouse Microbiota (OMM). The original OMM consists of 12 bacterial strains from the mouse intestine, herein termed OMM12.…”

Editorial: Employing Experimental Gnotobiotic Models to Decipher the Host-Microbiota Cross-Talk in Health and Disease

“…sought to explain the phenomenon behind elevated IgE levels in GF animals. Depending on the mouse facility, mouse model, and breeding conditions, GF mice exhibit elevated total serum IgE levels ( 6 – 9 ). Wyss et al.…”

“…The possibility to colonize GF animals with defined bacterial species or a consortium of bacteria has created a unique opportunity to evaluate the impact of the microbiota on host physiology and immune system (5). Colonization of GF mice with a defined bacterial consortium that mimics the complexity of a specific pathogen-free/specific opportunistic pathogen-free (SPF/SOPF) microbiota has increased the reproducibility of mouse experiments across different institutions and mouse facilities (6). In this regard, Eberl et al show that one such consortium, Oligo-Mouse-Microbiota12 (Oligo-MM12), could be established in several different animal facilities with excellent reproducibility.…”

“…Using the Oligo-MM12 consortium, Wyss et al sought to explain the phenomenon behind elevated IgE levels in GF animals. Depending on the mouse facility, mouse model, and breeding conditions, GF mice exhibit elevated total serum IgE levels (6)(7)(8)(9). Wyss et al demonstrated that colonization of mice with a well-defined composition of bacterial species is required to inhibit elevated IgE levels.…”