Animal Models for Microbiome Research Advancing Basic and Translational Science: Proceedings of a Workshop (2018) / Chapter Skim
Currently Skimming:
5 Experimental Reproducibility Using Gnotobiotic Animal Models
5 Experimental Reproducibility Using Gnotobiotic Animal Models
Pages 29-43
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 29... ...
Reducing microbiome-associated phenotypic variability is challenging for two reasons, said Macpherson. First, while the gut and skin microbiomes of a typical human remain relatively constant over a period of weeks, across individuals they vary tremendously.
|
From page 30... ...
He added that researchers should be aware that raising mice in vivaria protected from natural environmental pathogens would change the immunological maturity of the mice. TABLE 5-1 Different Types of Experimental Models for Understanding Microbiome-Associated Phenotypic Variability Bottom-Up Models Convergence Top-Down Studies Studying axenic models or Studying defined components Studies of complex and those with very simple of complex microbiotas natural microbiotas (e.g., Definition microbiotas, e.g., germ-free or (e.g., IgA-bound bacteria)
|
From page 31... ...
Moreover, it should express representative metabolic and immunological profiles, induce pathogen resistance and inflammatory response, and be relatively stable under aseptic husbandry conditions in individually ventilated cages. He and his team have designed the Stable Defined Moderately Diverse Mouse Microbiota 2 (sDMDMm2)
|
From page 32... ...
He added that, while studies with classical gnotobiotic animals with defined communities provide important insights about function, it might be important to take what these studies show and see if the results hold true in animals with a complex microbial community with other bacteria, viruses, fungi, and organisms. Franklin and his colleagues began exploring the issue of complex microbiota by looking at whether the gut microbial communities vary in contemporary rodent colonies.
|
From page 33... ...
As to whether mouse gut microbiomes are translatable to the study of human immune responses, he noted that a number of investigators are exploring this issue and finding that many organisms other than bacteria can trigger responses that would be useful for studying human diseases (Baxter et al., 2014; Beura et al., 2016; Chudnovskiy et al., 2016; Reese et al., 2016; Tan et al., 2016; Weldon et al., 2015; Wu et al., 2010; Zackular et al., 2016)
|
From page 34... ...
The consistency within a strain could, for example, result from maternal seeding, since all of the mice in a strain were derived initially from the same mother. To address that question, Lusis and his colleagues analyzed the genome sequences of the strains in the Hybrid Mouse Diversity Panel to map how they are related to one another given that they were all derived from a pool of pet mice around 100 years ago.
|
From page 35... ...
FIGURE 5-1 Microbial diversity in a population of 200 Finnish men ages 50 to 70 years (top) and across 113 mouse strains in the Hybrid Mouse Diversity Panel (bottom)
|
From page 36... ...
Lusis also discussed how he and his colleagues have been using host genetic variation to study host-gut microbe interactions. "If there is this big genetic component to the composition of gut microbiota, we should be able to apply genetic mapping to identify the genes responsible," he said.
|
From page 37... ...
From a practical perspective this implies that, when students leave his laboratory, they can re-create their animals in a new facility merely by taking a sample of the microbiota used to create the gnotobiotic animals and innoculating axenic animals housed at their new location. He noted that his research group has developed a robotic microbiota "manufacturing" system that can reliably assemble identical standardized microbial communities.
|
From page 38... ...
Going forward, Faith said that these types of immunological experiments would benefit from developing standard operating procedures designed to keep animals free from known pathogens and enable keeping microbiota reasonably constant for several generations. A goal for the research community, he added, should be to create a set number of microbiotas with different properties that a laboratory could order from a vendor to create a defined human microbiota in a mouse.
|
From page 39... ...
Animal studies, for example, enable tight control over defined diets for long periods, while germ-free animals allow researchers to examine the effect of diet independently of the gut microbe. It is fundamentally important, he said, to understand that diet not only shapes the composition of the microbiome but also serves as a substrate for the microbiota to produce molecules that can circulate widely throughout the body and affect distant organs (Holmes et al., 2012)
|
From page 40... ...
In addition, mouse digestive physiology and its response to diet is different from that of humans -- mice, for example, are hindgut fermenters and have a large cecum, whereas humans, who are not, have a small cecum -- and the response of the endogenous mouse gut microbiota to diet differs in magnitude and consistency relative to that in humans. As far as the studies themselves go, the lack of a standardized mouse chow and whether it is sterilized or not can be a cause of variance.
|
From page 41... ...
One conclusion, said Chervonsky, is that gender bias seen with type 1 diabetes does not depend on the specific microbial lineage. It is also possible, he noted, that the expansion of specific microbial lineages is also irrelevant to the gender bias of disease, but experiments with individual bacterial lineages showed that not all bacteria can influence a gender bias and that bacteria of very different families can affect gender bias.
|
From page 42... ...
42 FIGURE 5-2 Female and male differences in disease susceptibility related to immunological differences. NOTE: MERS, Middle East Respiratory Syndrome.
|
From page 43... ...
Experimental Reproducibility Using Gnotobiotic Animal Models 43 A so-called dual-signal model, in which both androgens and microbes work in concert to reduce type 1 diabetes in males, is more likely to explain gender differences, said Chervonsky. In this model, some hormones might amplify some microbes and some microbes might amplify hormone levels.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.