Monday, April 9, 2018

BacterioFiles 335 - Purported Paraprobiotic Potential

Lactobacillus bacteria
Pelzer et al. 2012
PLOS One e49965
This episode: Paraprobiotics, or killed probiotic bacteria, are studied for health effects, but results and study design are questionable!

Download Episode (11.5 MB, 12.6 minutes)

Show notes:
Microbe of the episode: Phlox virus S

Journal Paper:
Nishida K, Sawada D, Kawai T, Kuwano Y, Fujiwara S, Rokutan K. 2017. Para-psychobiotic Lactobacillus gasseri CP2305 ameliorates stress-related symptoms and sleep quality. J Appl Microbiol 123:1561–1570.

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  • Microbes help mice recover from bone marrow transplant (paper)
  • Lots of drugs other than antibiotics can harm gut communities (paper)
  • Using biofilm as camera film, for imaging

  • Post questions or comments here or email to Thanks for listening!

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    Episode outline:
    • Background: Probiotics: WHO def is “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”
      • Many benefits claimed, depending on organism and other conditions
      • Not all show benefit once going from lab animal studies to humans, or in replication
      • Complicated to study: have well-defined test group, genotype, cell status, delivery, dose
    • But evidence building that benefit doesn’t always require live microbes
      • Pieces of probiotics might be sufficient at least for some benefits
      • These treatments called “paraprobiotics”
      • Could be easier to study and more shelf-stable to deliver
    • What’s new: Now, scientists publishing in the Journal of Applied Microbiology have looked into some possible stress-reducing effects of a type of killed probiotic bacterium!
    • Lactobacillus gasseri CP2305, previously found some benefits in volunteers when live or killed
    • Methods: Recruited 2nd-year medical students in Japan as chronic stress model
      • Healthy but taking course in cadaver dissection
    • Gave either fermented milk, sterilized by heat, or placebo of lactic acid-soured milk beverage
      • Confirmed indistinguishable by test panels
      • Consumed daily
      • Then assessed general health, depression, anxiety, and sleep with questionnaires
        • Also gut symptoms and eating disturbances
        • Sig level of 0.05
      • And tested saliva for cortisol and other stress-related indicators
      • And use sequencing to check gut microbiota
    • General Health Questionnaire: lower scores are better
      • Paraprobiotic group scores didn’t change
      • Placebo group scores increased from ~18 to 20
      • However: treatment scores started out higher on average, statistics not impressive
        • Scores significantly different for women, not for men or all together
        • Could be sex difference
    • Sleep quality: here, scores improved for treated men and overall but not women
      • No other differences in general health questionnaires
    • Diarrhea: no significance except in men
    • No effects in salivary markers
    • Some changes in microbiota though, with treatment
      • Bacteroidetes phylum decreased
      • A couple genera changed, and 15 species
      • Nothing jumps out at me
      • Would've been helpful to do functional analysis of proteins and such, but hard
    • Summary: Giving inactivated probiotic bacteria didn't seem to have much effect on stressed medical students
    • Clarifications if necessary: Statistics were just t-tests
      • no indication of multiple comparisons correction
    • All questionnaire measures: treatment group started out higher
    • Says double-blind but no details given, just have to take their word
    • 2/6 authors from Asahi Group Holdings company that have milk-related products called Calpis or Calpico
      • Though claim no conflicts of interest
    • What do I think: Anyone doing probiotics research needs to hold to higher standards
      • Wouldn't say it's not worth researching, still value
        • Probiotics and also paraprobiotics
      • But so much junk already, gotta work hard to set quality apart
    • Perhaps more regulation of commercial probiotics could reduce motivation to low-quality?
    • Science self-correcting, find out truth in the end


    1. Do you think if this study were recreated using tighter methods and better data recording, that the same results would be replicated?

    2. Do you think that commercial products containing probiotics if looked at more strictly by the FDA would improve those that have claimed to have more probiotics within them than what is really there?

      1. Unfortunately, the FDA doesn't have much power to do much regulation of probiotics when they're sold as supplements. Probiotic production facilities are supposed to be run with Good Manufacturing Practices (GMP), but this is really only enforced if/after problems arise, not preventively, and doesn't really make any specific requirements about effectiveness or even safety of the product. Sellers of probiotics aren't allowed to make specific claims about treating disease, but they can make what are called structure/function claims, like "supports gut health" and such, that imply enough benefit that people want them (aside from people other than sellers making much more specific claims, only sometimes based on science).

        So FDA regulation doesn't do too much in the current system. But if the FDA had the mandate and resources to do more, I would expect the standards they set to be met more often than they currently would be (if there were standards). The FDA's regulation of pharmaceutical products works fairly well, for example. Of course it's not perfect, but with an FDA-approved drug one can at least have a reasonable expectation that there is a fair amount of science behind the claims the seller makes.