Lab mice are frequently seen as scientific duplicates—genetically identical and expected to behave identically. Yet, a recent study from Charles University's Faculty of Science reveals this isn't always true. Researchers discovered that gut microbiota composition can significantly impact immune system structure and function, even in genetically identical animals.
"The absence of microbiota led to increased variability in the mice," explains Jan Pačes, lead author from the Laboratory of Cell Immunology at Charles University. "Germ-free mice exhibited significant differences, while those with normal microbiota showed more uniformity."
Using a special "green mouse" model, which allows antigen-presenting cells to be seen under a fluorescent microscope, researchers conducted comprehensive quantitative mapping of gut-associated lymphoid tissues (GALT) in mice with various microbiota compositions: conventional (CV), germ-free (GF), and those colonized with the defined minimal microbiota OMM12.
The study found mice with complex microbiota were more similar to each other than GF or OMM12-colonized mice. The absence of microbiota led to greatly increased variability in gut immune organs. While OMM12 partially restored gut morphology, it did not restore physiological immune cell levels nor fully replicate the conventional mice's functional immune state.
During their research, the team also discovered a previously unknown immune structure—the immunovillus—mainly found in mice with restricted microbiota and potentially an adaptation to specific microbial environments.
The research, published in the journal Gut Microbes, emphasizes considering both genetic and microbial factors when interpreting data from lab mouse models. Standardization of microbiota is key for reproducibility, though current simplified consortia like OMM12 are not yet perfect substitutes for natural complex microbiota.