Monday, October 16, 2017

BacterioFiles 314 - Drosophila Dwellers Delay Deficiency

Drosophila fruit fly
By André Karwath aka Aka
CC BY-SA 2.5
This episode: Bacteria affect fruit fly behavior by reducing their need and craving for protein-rich food!

Thanks to Dr. Carlos Ribeiro for his contribution!

Download Episode (14.7 MB, 16.1 minutes)

Show notes:
News item

Ribeiro lab website - two fully-funded postdoc opportunities available

Journal Paper:
Leitão-Gonçalves R, Carvalho-Santos Z, Francisco AP, Fioreze GT, Anjos M, Baltazar C, Elias AP, Itskov PM, Piper MDW, Ribeiro C. 2017. Commensal bacteria and essential amino acids control food choice behavior and reproduction. PLOS Biol 15:e2000862.

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    Episode outline:

    • Background: Microbiota depend on us eating for food
      • They eat what we eat, or make out of food
    • But different microbes like different kinds of food
      • Unhappy if we don’t eat those kinds, or eat too much of rivals’ preference
    • Can they influence our preference for foods at all?
    • What’s new: Now, scientists publishing in PLOS Biology have discovered that specific bacteria in fruit flies affect their appetite for certain types of food! The authors on this study are: names. That was Dr. Ribeiro, A PI
    • Statement 1
    • Fruit fly Drosophila melanogaster
      • Likes to eat sugary stuff usually, like sap/nectar
      • But driven to eat yeast sometimes, when reproducing or not getting enough yeast
      • Statement 2
      • Don’t know exactly enzymes/nutrients that drive latter appetite, wanted to find out
    • Methods: Gave fruit flies artificial diet that imitates yeast, cos yeast too complex
      • Dr. Ribeiro describes: 3
      • Works to make them stop wanting it, so must contain essential nutrient
      • Found that amino acids/proteins, when removed, made fruit flies want yeast
      • Removing other nutrients didn't have same effect, even vitamins essential for reproduction
    • Given choice of diet with sugar but no protein vs. protein but no sugar
      • Normally flies preferred sugar
      • But when in yeast-eating mode, preferred protein
    • Also, logically, only amino acids that flies can't make themselves induced craving
      • Though when already craving, any amino acids satisfy
      • Also works with flies mutated to not be able to make an amino
    • However, it was not always so straightforward: statement 4
      • Gave flies combo of 5 cultured bacteria from normal fly community
      • Lactobacillus plantarum, Lactobacillus brevis, Acetobacter pomorum, Commensalibacter intestini, Enterococcus faecalis
      • And flies no longer had yeast craving, even when all essential aminos removed
      • Doesn't work with killed bacteria; not just acting as food
      • Also doesn't work with mutant flies that can't produce own aminos; only specific essentials
      • Narrowed community down to 2 needed: Aceto and one of two Lactos (either)
    • Is all this good for fly?
      • Getting protein important for reproduction/egg production
      • But with bacteria, flies could produce more eggs even when deprived of essential aminos
      • Flies like eating food with these bacteria more than without
      • But don't actually get more aminos; bodies don't contain more than deprived controls
      • Apparently just don't need as much yeast
    • Summary: So here's the summary, from Carlos: summary
    • Applications and implications: Step closer to understanding fruit fly cravings, though still don't understand exact mechanisms
    • Most important is implications about bacterial influence; Dr. Ribeiro again: statement 5
      • Need for yeast can influence other behaviors in flies, like risk-taking; thus bacteria too?
    • What do I think: Community specifically evolved for this fly
      • Fly strains mutated to not produce others might have different bacteria
      • Or might need further mutations to adapt, not sure
      • Having different microbes might be helpful in different environments
      • Interesting to see how the two microbes each act so as to both be needed
    • Ep 217, fruit flies carry own yeast to help get more proteins out of low-quality food
      • These bacteria help in different way
    • Weird that flies only crave AAs and not vitamins; maybe too hard to evolve
      • Or AAs act as proxy for everything contained in yeast
      • Be careful to make sure any diets are comparable, in context
    • If microbe-free flies could do just as well with more microbes and less yeast
      • Must not need all the yeast they're eating?
      • Not surprising that lab-grown flies wouldn't be quite same as those in nature
      • Maybe like humans have appetite for food we don't need, get fat
      • Possible that the right bacteria could help prevent this in us too
    • There are a lot of potential future discoveries in this area, so Carlos has plans: statement 6
    • And so if any of my microbiologist listeners are interested in doing research in Portugal, this could be an opportunity: statement 7
    • I'll put a link to the lab website in the show notes!

    Carlos Ribeiro Transcript:
    We just published a paper in which we show that two gut bacteria in the Drosophila melanogaster fly alter the food preferences of the flies.

    In our lab, we want to understand how animals decide what to eat. Or in other words, how does the brain know which nutrients are missing in the animal, and use that to then change its food preferences and then make that the animal eats that nutrient to compensate for its lack.

    In fruit flies, one of the main nutrients is actually yeast. That's kind of the steak of the animal. That's where it gets proteins, vitamins, and other important nutrients from. And we had shown previously that flies have a strong craving for yeast when you remove yeast from their diet. And so we started asking, what induces that craving for yeast?

    And for this we turned to a new reagent, which we had co-developed with Matt Piper, which is a fully synthetic diet for flies which recapitulates all nutritional needs of the animal. And because this diet is fully chemically defined, we can remove all different nutrients and look what induces craving for yeast.

    But we had a problem. Which was sometimes, we removed amino acids from the diet, and flies had a strong appetite for yeast, and in some animals, when we removed essential amino acids, there was absolutely no effect. And that was driving us a bit crazy, until we sat down and looked at these animals and realized it looked like these animals which didn't develop the craving for yeast were actually having some bacteria growing in them. And that's when we realized that most of our flies in our fly facility, which is a very clean environment, don't have gut bacteria. And that the animals which had gut bacteria were protected from having a mounting yeast appetite. And that's what led us into looking which type of gut bacteria influence food cravings

    we identified two specific bacteria, Acetobacter pomorum and either Lactobacillus plantarum or Lactobacillus brevis, which when they're present in the animal, the animal is protected from the physiological effect of lacking amino acids, which is a reduction of egg production, and also there is no yeast or protein craving induced in the animals which have these two bacteria in their stomach. Which means that these two bacteria are able to talk to the brain and suppress yeast craving.

    So somehow these two gut bacteria when they are present, they kind of reprogram the metabolism and the behavior of the animal so that they can better deal with the lack of essential amino acids, by producing more eggs when they don't have essential amino acids, and also that leads to the fact that they don't induce a yeast appetite and that's good and beneficial for the animal because eating a lot of protein actually shortens lifespan.

    We think that these findings are really important because first of all they are the first proof that gut bacteria, the microbiome, can have specific effects on food cravings. And also we think that it generally shines a light on possible mechanisms of how gut bacteria could alter behavior. Which is by tapping into the nutrient-sensing abilities of the brain and therefore altering the behavioral output of the animal.

    Obviously there is a lot of new things now we want to follow up, first of all, what's happening in the host when we have these two gut bacteria, so we have done a lot of RNAseq data and a lot of genetics now in the host, a lot of brain imaging to look at how the brain now works with or without these microbes, And also now we're starting to do microbial genetics to do screens in these microbes because we know exactly which microbes give the effect, to start asking why do you need two microbes to have that effect, and how do the microbes alter behavior, which genes in the microbes are required to alter the behavior of the host, and which are the mechanisms actually which the microbes use to alter behavior,

    and we are really excited now to be recruiting a microbiologist to join the lab, to really now start working on this fascinating topic, which is microbial genetics and the microbiome, and I think we have a great system to understand how microbes affect behavior.

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