House mouse, Mus musculus domesticus |
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Show notes:
Microbe of the episode: Cabassou virus
News item
Journal Paper:
Rosshart SP, Vassallo BG, Angeletti D, Hutchinson DS, Morgan AP, Takeda K, Hickman HD, McCulloch JA, Badger JH, Ajami NJ, Trinchieri G, Pardo-Manuel de Villena F, Yewdell JW, Rehermann B. 2017. Wild Mouse Gut Microbiota Promotes Host Fitness and Improves Disease Resistance. Cell 171:1015-1028.e13.
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Episode outline:
- Background: Studying microbiota in animals immensely helpful
- Lots of things can be done not possible elsewhere
- Like last episode
- But gotta keep limitations in mind
- Ep 186, mouse microbes different in different rooms of building
- Mice generally kept with somewhat artificial microbiota
- Called SPF, specific pathogen-free
- Or even germ-free, no microbes at all
- Good for studying what effects microbes CAN have, but practical effects in real world?
- What’s new: Now, scientists publishing in Cell have discovered that the wild microbes wild mice have in the wild really make a difference in the health of the mice!
- Methods: Lab mice derived from house mice and other subspecies
- Mus musculus domesticus from Maryland
- Mostly lives in woods and fields, moves into buildings sometimes when cold
- Scientists trapped 800 in horse barns around Maryland and DC
- Narrowed down to 98 by maturity, species, etc
- Compared to 21 populations worldwide; these are closest to lab animals
- Analyzed gut microbes from mice
- Clustered together, even mice from different barns
- But significantly different from lab mice
- Wild had more Bacteroidetes, Proteobacteria, less Firmicutes etc
- Lab ones have mostly Firmicutes, wild more balanced though
- Screened wild mice for pathogen exposure
- Found antibodies against normal ones, but no signs of disease
- Also not found in microbes
- So took microbes and introduced into germ-free lab mice
- 1st of 3 doses went into pregnant mice, to see vertical transfer
- As control, inoculated others with lab communities
- Controls’ communities were same as normal lab mice
- So inoculating works
- Mice inoculated from wild microbes were distinct from each
- Stable over generations
- Close to wild but not identical
- Very different from lab community
- So what effect of wild community?
- Challenged each with mouse-adapted influenza
- Only 17% of lab microbe mice survived
- 92% of wild microbe mice
- Also less weight loss, lower viral titers, less organ damage
- Also tested with other disease: gut tumors induced by mutagen and inflammation
- Chemical azoxymethane and dextran sodium sulfate
- Wild microbe mice had less weight loss, fewer and smaller tumors
- Also less invasive
- Summary: Lab mice with gut microbes from wild mice more resistant to infection and even inflammation-associated cancer than if they have normal lab mouse microbes
- Applications and implications: Study these mice in more detail
- Learn about how microbes can contribute to these health effects
- Make mouse models more reliable in general, more representative
- What do I think: Why I always feel need to mention mouse study
- Just not safe to assume extrapolation
- Possible a lot of results in mice are just artifacts of lab conditions
- Amazing to see how much difference gut community can make
- Some, like Dr. Martin Blaser, are concerned
- Are we humans making ourselves like lab animals?
- Overexposure to antibiotics and other antimicrobial chemicals
- Deplete important microbe communities and become less healthy
- Too much extrapolation, of course, but worth considering when possible
- Hard to replace microbes specific to us if lost from population
- Need to develop more harmony with microbial world
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