The Altered Schaedler Flora: Continued Applications of a Defined Murine Microbial Community

Abstract

The gastrointestinal (GI) microbiota forms a mutualistic relationship with the host through complex and dynamic interactions. Because of the complexity and interindividual variation of the GI microbiota, investigating how members of the microbiota interact with each other, as well as with the host, is daunting. The altered Schaedler flora (ASF) is a model community of eight microorganisms that was developed by R.P. Orcutt and has been in use since the late 1970s. The eight microorganisms composing the ASF were all derived from mice, can be cultured in vitro, and are stably passed through multiple generations (at least 15 years or more by the authors) in gnotobiotic mice continually bred in isolator facilities. With the limitations associated with conventional, mono- or biassociated, and germfree mice, use of mice colonized with a consortium of known bacteria that naturally inhabit the murine gut offers a powerful system to investigate mechanisms governing host-microbiota relationships, and how members of the GI microbiota interact with one another. The ASF community offers significant advantages to study homeostatic as well as disease-related interactions by taking advantage of a well-defined, limited community of microorganisms. For example, quantification and spatial distribution of individual members, microbial genetic manipulation, genomic-scale analysis, and identification of microorganism-specific host immune responses are all achievable using the ASF model. This review compiles highlights associated with the 37-year history of the ASF, including descriptions of its continued use in biomedical research to elucidate the complexities of host-microbiome interactions in health and disease.

Response of Germfree Mice to Colonization by Oxalobacter formigenes and Altered Schaedler Flora

“…Post hoc analysis showed that the wet weights of ceca from ASF or ASF/OxF animals were significantly lower than those from the GF and GF/OxF groups. These data are consistent with previous studies that showed that GF and monocolonized mice displayed enlarged ceca, whereas colonization of GF mice with ASF resulted in smaller ceca of similar morphology, compared with ceca from conventional mice (16,40). In keeping with total cecal oxalate levels (Fig.…”

“…Germfree rats, for example, show increased absorption of minerals, including calcium (60), and are susceptible to forming calcium oxalate-containing stones in the bladder (61). In contrast, ASF mice have normal-size ceca and normalized intestinal functions (16). It is possible that improved intestinal epithelial integrity in ASF and ASF/OxF mice, compared to GF and GF/OxF animals, resulted in lower net gastrointestinal oxalate absorption, which in turn could explain the lower levels of urinary oxalate excretion in ASF and ASF/OxF animals than in GF and GF/OxF animals.…”

“…A specific example of selective colonization of germfree (GF) animals involves the altered Schaedler flora (ASF), consisting of eight normal murine bacterial species. ASF mice have been in use for decades and offer significant advantages for the investigation of mechanisms governing host-microbiota relationships and how members of the gastrointestinal microbiota interact with one another (16). Of note, the genome of one of the ASF bacterial species, Lactobacillus intestinalis, contains oxalylcoenzyme A (oxalyl-CoA) decarboxylase and therefore may have the capacity to degrade oxalate.…”

Altered Microbiota Composition Mediates Depressive Behavior During Chronic Stress

“…This result is likely due to the devastating dysbiosis that broadspectrum antibiotic treatment causes, which cannot be restored by a single bacterial species. Dramatic cecal enlargement is a phenomenon observed in antibiotic-treated mice, as well as germ-free mice, and is a measure of their intestinal health 119,170 . The re-colonized mice remained enlarged, showing only a mild amelioration in their cecal size (Fig.…”

“…corresponding to the most abundant genuses observed in the mouse and human microbiomes 170,171 . Since the flora is introduced by individual cultures of component bacteria, the Lactobacillus species can be left out, thus resulting in a balanced flora missing a specific component.…”