Monday, October 30, 2017

BacterioFiles 315 - Probiotics Prevent Protein Plaques

Credit: National Institute on Aging
This episode: In mice genetically modified to have Alzheimer's-like disease, giving probiotics reduced their degeneration!

Download Episode (11.8 MB, 13 minutes)

Show notes:
Microbe of the episode: SARS coronavirus

Journal Paper:
Bonfili L, Cecarini V, Berardi S, Scarpona S, Suchodolski JS, Nasulti C, Fiorini D, Boarelli MC, Rossi G, Eleuteri AM. 2017. Microbiota modulation counteracts Alzheimer's disease progression influencing neuronal proteolysis and gut hormone plasma levels. Sci Rep 7:2426.

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    Episode outline:

    • Background: Seems like every disease/body issue has some connection to microbes
      • Either they influence it or it influences them, or both
    • Most microbes live in gut, but metabolites and signals can spread from there everywhere
      • Different organs, even brain
    • What’s new: Adding to this list of body issues and tissues affected by microbes, scientists publishing in Scientific Reports have discovered that gut microbes could even influence the development of Alzheimer’s disease!
    • Alzheimer’s: neurodegeneration, loss of memory, judgment, and ability to function
      • Hard to take care of people with it, no good reliable treatment or prevention yet
      • Characterized by buildups of certain proteins in brain
    • Some hormones known to be involved in appetite and metabolism, ghrelin and leptin
      • Also affect brain functions and help protect against Alzheimer’s-related protein buildups
    • Thus, link between gut and brain
    • Methods: Mice used were transgenic, produced human versions of proteins involved in AD
      • Amyloid beta and tau
      • Reliable model of human AD, saw evidence as early as 3 months
    • Treated with either water or mix of probiotic bacteria
      • Streptococcus thermophilus, Bifidobacterium longum, breve, and infantis, and Lactobacillus acidophilus, plantarum, paracasei, delbrueckii subsp. bulgaricus, and brevis
    • Tested with trials called Novel Object Recognition and passive avoidance
      • Novel Object: give mice 2 identical objects for a while, then replace with 1 same and 1 new
        • Measured how long they spent exploring each to give discrimination score
        • Test of memory, see if they recognized new object as new and familiar as familiar
      • Passive avoidance: give mice mild shock to foot when it enters dark chamber
        • See how long/strong it keeps memory of that unpleasantness
      • Both memory tests but two different types of memory
    • At 18 weeks (~4.5 months), treated mice had better memory scores with novel objects
      • No diff at 24 weeks though, mice not motivated to explore anything anymore after so much
      • Tried again only testing twice, compared with wild-type mice
        • Then saw difference at 24 weeks in AD mice, no diff in wt
    • With passive avoidance, not much difference with treated vs. untreated; all could remember
      • Conditioning memory not affected by AD
    • Treated mouse brains also stayed same weight, while controls decreased
      • And specific areas of untreated brains lost thickness
    • Gut microbes of AD mice had some differences from wild-type
      • Reductions in some related to health
      • But probiotic treatment only had few specific changes: more bifidobacteria, for example
      • Does change microbiota functions though, like metabolism and DNA repair
      • Also more SCFA production vs. control mice, leading to less inflammation
    • As mentioned, some metabolic hormones affected in AD
      • So tested levels in different mice
      • No change with probiotics or not in wild-type mice
      • AD mice had decreased levels of hormones
      • But treatment with probiotics increased levels
    • Probiotics also reduced amounts of toxic amyloid plaques
    • Also increased activity of enzymes that break down problematic protein buildups
    • Summary: Treating mice with mix of probiotic bacteria decreased memory loss and problematic markers associated with Alzheimer's disease
    • Applications and implications: Potential treatment for Alzheimer's
      • If works out similarly in humans; takes a lot to test
    • Probiotics straight, or other modulation of microbes, or affect things more directly
      • Could reduce a lot of suffering
    • What do I think: Context: mice in this study got 200 billion bacteria per kilogram per day
      • ~5 billion per 25g mouse
      • 150-lb/68kg human would need 13.6 trillion per day
      • Can buy box of 30 pcs Culturelle probiotic with 10 billion bacteria for $15
        • Only one species, not 9
      • 45 boxes per day, or $680
      • Maybe cheaper than some medications on market though!
    • Effect almost too good to believe
      • Which is good science, to hold off conclusion until other studies replicate effect
      • Many have shown such incredible benefits from probiotics
        • In all different ways and areas of the body
        • And it is plausible
      • And many studies have not shown much effect
    • We'll just have to see how the science works out!

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