BacterioFiles 327 - Microbe Metabolite Meliorates Malaise

Influenza virus particles

This episode: Gut microbes in mice break down plant foods and produce molecules that stimulate the immune system to resist influenza!

Thanks to Drs. Ashley Steed and Thaddeus Stappenbeck for their contributions!
Download Episode (9 MB, 9.8 minutes)

Show notes:
Microbe of the episode: Bougainvillea chlorotic vein banding virus

News item

Journal Paper:
Steed AL, Christophi GP, Kaiko GE, Sun L, Goodwin VM, Jain U, Esaulova E, Artyomov MN, Morales DJ, Holtzman MJ, Boon ACM, Lenschow DJ, Stappenbeck TS. 2017. The microbial metabolite desaminotyrosine protects from influenza through type I interferon. Science 357:498–502.

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Episode outline:

• Background: Influenza often thought not very serious
• But kills thousands of people each year
• Young children and elderly most at risk usually
• Vaccine helpful but not always very good match with circulating strain of flu
• Egg-based versions bad this year cos of process growing virus in eggs
• Need to develop more good approaches
• Can be hard to predict individuals most at risk
• Here’s Dr. Ashley Steed, pediatrician and researcher at Washington University School of Medicine: statement 1
• What’s new: Now, Drs. Steed and Thaddeus Stappenbeck and colleagues, publishing in Science, have discovered how a certain microbe in the guts of mice helps protect them from influenza!
• Gut microbes surprisingly important for immune function
• Ep 196, microbes important for vaccine effectiveness
• Also studies showing microbes important for protection directly
• Methods: Thought microbial metabolites might mediate effect
• Screened 84 using cell culture
• Looking for influence on immune molecule interferon
• Important signal to mount antiviral response
• Confirmed important using mice that overproduce it; especially resistant to flu
• Statement 3
• Product of microbial breakdown of compounds called flavonoids
• Various chemicals common in some plant foods: berries, tea, parsley, citrus, etc
• Mice given antibiotics had no fecal DAT
• Also less resistant to flu, as shown before
• Screened mouse microbes for DAT production, found one especially: Clostridium orbiscindens
• Here’s the study’s last author, Dr. Stappenbeck: statement 2
• Pretreating with DAT directly increased flu resistance
• But not treating after infected already
• Statement 4
• Summary: Mice were more resistant to flu when had Clostridium orbiscindens degrading flavonoids to desaminotyrosine, which stimulated immunity via interferon
• Applications and implications: Interaction of diet and microbiota could influence resistance to viral infection, even respiratory
• DAT or similar compound previously found after supplementation of grape seed flavonoids
• Here flavonoid tested with microbes in culture was quercetin
• Found in many fruits and vegetables, especially colorful ones
• Figure out if similar effect in humans, and if possible to help more people have this effect
• Give microbe, or metabolite, or whatever combo needed
• More prevention than treatment though
• Possible implication: giving antibiotics for flu not just unhelpful, but possibly harmful
• Clarifications if necessary: Mice
• Eating healthy good in many ways, this could be one
• Worth doing all the time, but maybe especially in winter
• What do I think: Why gut microbes so helpful?
• Obvious anthro-centric answer is, good for them if host survives
• But too simplistic; how would effect be achieved via evolution?
• And requires interplay between microbes and our gut and immune system in response
• Microbes helpful in general for calibrating immune system
• Possible they just help achieve best balance
• Even microbes helpful sometimes can cause overactive immune system in other cases
• Complex but as always, take care of your microbes!

Transcript:
Steed:
1
Some patients get very sick, and others don't get sick at all, and you wouldn't even know that they had an active infection going on. And so we wondered if differences in the microbiome potentially could have implications for that human variation in influenza.

Stappenbeck:
2
This microbe's great at degrading flavonoids, so it's really great at that, and we picked a couple other microbes that are cousins to this particular microbe; similar but not identical properties. And they couldn't degrade flavonoids. And then the exciting thing is when Ashley put these microbes into mice and then gave them influenza, it was the Clostridium orbiscindens species that could protect from flu, but not the others.

Steed:
3
So we screened a number of metabolites, 84 in fact, and we found one that reproducibly acted in that fashion, and that was desaminotyrosine.

Stappenbeck:
4
Desaminotyrosine didn't prevent the flu infection or didn't lessen it, the level of infection was basically the same. It was the consequences of the infection was really dampened by desaminotyrosine.