Monday, May 14, 2018

BacterioFiles 338 - Maverick Mouse Microbes Mitigate Maladies

House mouse,
Mus musculus domesticus
This episode: Gut microbe transplants from wild mice protect lab mice from disease!

Download Episode (9.8 MB, 10.7 minutes)

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.

Other interesting stories:
  • Phage cocktail can eliminate pathogen with minimal collateral damage
  • Preventive probiotics given with antibiotics can help keep C. diff away
  • Early exposure to dust and bacteria linked with less immune response to stress
  • Viruses that help wasps parasitize caterpillars also inhibit plant defenses
  • Only one microbe species can live in extremely acidic, almost boiling lake

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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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