Use of gnotobiotic mice to identify and characterize key microbes responsible for the development of the intestinal immune system

Abstract

Symbiosis between intestinal microbiota and the host animal plays an important role in the homeostasis of host physiology. Since the first production of germ-free rodents in 1945, it has become increasingly clear that the intestinal immune system and the biochemical characteristics of epithelial cells differ greatly between conventional and germ-free rodents. However, questions remain about the types of microbes involved and the precise mechanism by which these microbes affect the host physiology. Here, we review experiments designed to answer these questions with the use of gnotobiotic mice. We have determined suitable biochemical and immunological markers for monitoring microbial effects in these mice. Using these markers, we have found clear differences in epithelial cell glycolipid biosynthesis and intraepithelial lymphocyte dynamics between germ-free and conventional mice. Furthermore, we have identified a key microbe that activates the mucosal immune system in the small intestine. This indigenous bacteria, called segmented filamentous bacteria, is a key symbiont in the host-microbiota interplay, including Th17 cell-inducing activity.

A potential role for the gut microbiome in substance use disorders

“…For investigation of the effects of the gut microbiome on behavior, one of the more common paradigms is to use germ-free animals that are raised in a sterile environment from birth and lack any internal or external microbiome (Faith et al 2010). Germ-free animals are often compared to specific pathogen-free (SPF) or conventional animals, both of which possess a normal, complex microbiome (Umesaki 2014). Germ-free animals can be colonized with both simple and complex microbial communities from donor animals or human subjects in a process known as conventionalization; this allows researchers to interrogate the contribution of a defined donor microbiome to a phenotype of interest (Faith et al 2010).…”

Selective Manipulation of the Gut Microbiota Improves Immune Status in Vertebrates

“…To analyze gene expression (metagenomics), protein products (metaproteomics) and metabolic profiles (metabolomics), GF animals emerge as an indispensable tool, which may help to decipher the microbiome composition, metabolic activity, and mechanisms used by microbiota in health and disease ( 50 ). This tool has already greatly contributed to understand the development of the vertebrate immune system, physiological processes, and the mechanisms responsible for inflammatory and neoplastic diseases ( 18 , 51 – 54 ). Gnotobiotic models, a variant of GF models, are organisms with a defined microbiota, which can range from a single bacterial species to a known consortium, introduced alone, together, or sequentially in the host.…”

The Microbiome and the Liver: The Basics

“…[29][30][31][32] The maturation of the gut-(or mucosa-) associated lymphoid system (GALT or MALT) is retarded in germ-free mice, as evidenced by smaller Peyer's patches, decreased plasma cells, a deficiency in IgA secretion, and impaired barrier function. 33,34 These defects are reversed by colonization (also referred to as conventionalization). 35 Slack and colleagues explored the interplay between the gut microbiota and the adaptive and innate immune systems in the germ-free mouse, and revealed the critical role of the host immune system in sustaining tolerance and in minimizing access for gut bacteria to the portal circulation.…”