Technology

GNOTOMICE

Standardized gnotobiotic mouse model harboring a 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes.

Wordcloud Gnotomice

Objectif/Description technologique

BIOASTER has developed and validated a standardized gnotobiotic mouse model comprises 15 bacterial strains (GM15).

GM15 is a simplified and controlled murine gut microbiota and its related to gnotobiotic mouse model. The GM15 community is composed of pure cultures of 15 strains from 7 of the 20 most prevalent bacterial families present in the fecal microbiota of C57BL/6J SOPF mice. GM15 carries significant potential for enzymatic activities in the gut and recapitulates extensively the functionalities found in C57BL/6J SOPF gut microbiome. GM15 is stable upon adult colonization for up to 12 months, during natural transmission among nine filial generations, upon mild dietary fluctuations, can be transmitted efficiently by FMT, and can be re-established efficiently in another gnotobiotic facility. GM15 compensates breeding, growth, immune, endocrine, and metabolic limitations of GF mice and recapitulates many SOPF animals’ phenotypical features in a reproducible manner in two gnotobiotic facilities.

GM15 gut microbiota isolated from C57BL/6J mice

Background

The gut microbiome plays a major role in animal and human health. Thus, there is a need for reproducible animal models with standardized gut microbiota.
Despite global efforts to standardize breeding and experimental procedures, the undefined composition and interindividual diversity of the microbiota of laboratory mice result in several limitations:

  • Reproducibility and robustness of preclinical studies are affected by the confounding effect of fluctuation in microbiota composition
  • Understanding mechanisms through which gut microbiota takes part in health, and through which dysbiosis contributes to disease is limited

Within this frame, we have developed the GM 15 model aiming to:

  • Identify a representative and simplified microbial consortium by in silico design
  • Isolate defined bacterial strains from the feces or the caecum of C57BL/6J specific and opportunistic pathogen-free mice
  • Colonize germ-free mice with the GM15 consortium on a stable and long-term basis, and in two different animal facilities
  • Monitor with a rapid and sensitive assay the microbiota composition
  • Characterize the macroscopic, immune, endocrine and metabolic phenotypic profile of the GM15 mouse model and compare it to the SOPF standard
  • Assess the impact of post-weaning malnutrition on host physiological response

Advantages

GM15 mouse model benefit the scientific and industrial community by providing in vivo experimental evidence sustaining the causal link between a given microbiota and health or disease.

In addition, the GM15 model offers exciting perspectives for preclinical research focusing on drug-host-microbes interactions to evaluate antimicrobial resistance and the impact of drugs on commensals and on the intestinal barrier function. Finally, the GM15 model with its simplified gut microbiota also offers the possibility to use it as a template for establishing customized and further complex consortia to investigate specific biological questions.

Potential Applications

GM15 model offers possibilities for preclinical research focusing on host– microbe and microbe–microbe interactions, and how the microbiota shapes the environmental impact on health and diseases or drug efficacy. Thus this model allows to:

  • evaluate antimicrobial effects (dysbiosis) and resistance, as well as the effects of drugs on commensals and intestinal barrier function using a standardized mouse model which comprises 15 bacterial strains that are representative of the most prevalent bacterial taxa in the mouse fecal microbiota,
  • provide a reproducible mouse model to aid understanding of the role of the gut microbiota in the health-disease transition phenomenon, its prevention and/or treatment,
  • use the model as a surrogate to establish customized and more complex consortia to investigate specific biological questions.

Outlook

To demonstrate the use of GM15 model in different application fields, such as but not limited to metabolic research (malnutrition, obesity), immunology including allergy (prophylactic or curative treatment), cancer research (e.g. immunomodulatory effect of microbiota during anti-cancer therapies) and vaccine development or microbiota- (commensal/pathogenic bacteria, viruses [prokaryote or eukaryote], fungi) host interactions allowing a better understanding of health-disease transition.

An example in the field of infectious diseases, one of the areas attracting considerable attention and utilizing the gnotobiotic animal model is that of the host–pathogen interrelationship. Over the past decades gnotobiology showed promise and in many cases demonstrated its relevance in analyzing protective function of microbiota of gnotobiots to bacterial or viral infections.
BIOASTER is welcoming partners willing to re-risk their product development using GM15 model either within the frame of a co-development or within a consortium.