Probiotics: Regulation and Research Insights

Do probiotics really seed or populate your gut?

How do you decide which strain or species of probiotic to take? Do certain compounds enhance the efficacy of probiotics? Should probiotics be personalized?

I tackle all these probiotic questions and many more in today's episode with Raja Dhir.

Raja the Co-Founder and Co-CEO of Seed, an ecosystem of kindred scientists, doctors, innovators, entrepreneurs, and translational storytellers from around the world. Seed's members collectively believe in the potential of the microbiome to improve human and planetary health.

Raja leads Seed’s research strategy and academic collaborations, clinical trial design, product development, and intellectual property strategy. He is the architect of the Seed Platform and has unique expertise in translating scientific research for product development – including patented inventions to stabilize sensitive compounds to improve human microbiome diversity and inflammatory biomarkers.

He’s also the Co- Chair of Seed’s Scientific Advisory Board where Seed focuses on solving complex ecological problems including honeybee colony collapse, plastic degradation, and soil fertility through bacteria. Raja is an Entrepreneur-in-Residence at the Church Lab in the Department of Genetics at Harvard Medical School and is a Director and Co-Chair of the Scientific Advisory Board for Micropia, a $20MM microbial ecology / education platform and the world’s first museum dedicated exclusively to microbes.

He also serves on the Editorial Board for the scientific journal, Microbiome, on the Industry Advisory Committee for the International Scientific Association for Probiotics and Prebiotics (ISAPP), and is a member of the New York Academy of Sciences (NYAS), the American Society for Microbiology (ASM), and the American Association for the Advancement of Science (AAAS), among others.

During our discussion, you'll learn: -Why we misunderstand probiotics, and especially probiotic research...8:30

• Raja's research paper: Probiotics: What they are and what they are not
• We're understanding more and more about the gut and microbiome every day
• An organism must show that it has a specific effect on the body before the term "probiotic" can be used
  • The term "probiotic" is unregulated in the United States
  • Consumers are way ahead of the science
• Proper definition of a probiotic: live microorganisms, which when administered in adequate amounts confer a health benefit on the host
• Unscientific research on probiotics has led to damage in credibility in the field
• Taking one single data set that's not causative and applying the results to the entire field is an unscientific practice

-The recent studies on probiotics that Raja mentions, and sometimes criticizes, in his work...13:45

• Conducted by the Weizmann Institute
  • Got subjects to consent to invasive small intestinal biopsies, versus just the colon
  • Ordinarily you test the large intestine only
• An over emphasis on testing stool samples
• Fallacy: Collecting large amounts of data will give you an accurate answer
• How classical biologists are different:
  • Have a hypothesis,
  • Narrow down an intervention,
  • Test (in a large enough sample size) and look for biomarkers that change in the host
• How the test worked:
  • Gave 3 groups of people large amounts of antibiotics
  • Gave one group probiotics, one group allowed to recover spontaneously (watchful waiting), third group FMT; their own stool injected back in rectally
  • Hypothesis: What's the fastest way of recovering to your normal base line?
  • After 90 days, everything lost statistical significance; all 3 groups indistinguishable from one another
• 3 things you can do to improve an infant's health
  • Vaginal birth
  • Not having antibiotics during birth (if you have a c-section)
  • Breast feeding
  • Do at least 2 of the 3 correctly, you dramatically increase the chances that the infant's microbiome will develop normally
• Science should not be a sensationalistic field
  • Temptation to exploit research for short-term PR gains

-What regulations or standardizations exist when it comes to the microbiome and probiotics...23:25

• Contract manufacturers: used by big dairy companies, big business, probiotics found in local grocery stores
• European facilities are better equipped due to dietary differences
• Species vs Strains:
  • Ex: Chihuahuas and dobermans are different strains of the same species
  • Some strains are up to 70% different from strains of the same species
  • Must be tested on humans, otherwise should be called a microbial product vs. a probiotic product
• Some less disciplined companies benefit from the existing ambiguities in the probiotic field

-Raja's answer to the flaws in probiotic research he discusses in his paper and in his work...27:15

• The paper concludes with an optimistic view; possible changes in the next 5 years
  • Click here for a table of Physiological and metabolic processes influenced by the human microbiome according to Raja's research paper.
• Activating a switch in the body that prevents and reverses food allergies
• Minimum requirements before anything should call itself a probiotic
  • Declare the genus, the species and the strain
  • Undergo minimum one human clinical trial
• If you didn't get all that, get this: While there is tremendous potential and reason for optimism in the field of probiotics, overuse of the term in the media and commercial use "cheapens" it and could discourage serious scientists from pursuing it to its full potential.

-How (or if) probiotics interact with the microbiome...34:30

• Article: Human gut study questions probiotic health benefits
• Probiotics are "transient microbes"; they don't take up permanent residence in any part of the body
• "Seeding" is the process by which an infants microbiome is first colonized by microbes
• Typical time a probiotic stays in the microbiome is ~8 weeks
• Daily consumption is necessary (kind of like coffee)
• Why not just eat fermented foods all the time?
  • Only 4-5 out of several hundred bacterial strains in kimchi had probiotic potential (by the standards laid out in Raja's paper)
  • Kombucha companies should do randomized controlled trials
  • Terms like "immunity" and "anti-inflammatory" are misleading
• Certain bacteria can become "extinct" in as little as 4 generations when fiber is removed or reduced
• Certain populations do not need to take a probiotic because of their lifestyle and diet (ex. the Hadza people)
• "Detoxification" is oftentimes a misnomer;
  • The body has its own detoxification pathways that are regulated by the nrf2 transcription factor
  • Triggers for activation of the pathways: extended exercise, access to wide variety of phytonutrients,
  • Things that are bad for you are good for you

-The varying effects from different species and strains of probiotics...46:35

• Biotransformational nutrients: take existing food particles and convert into secondary metabolites and unlock new nutrients
• Probiotics supplement the existing micronutrients and gut bacteria
• "Consuming little soldiers that make their own multi-vitamins"
• Pomegranate is standardized for punicalagin: turned by already existing bacteria in the gut into Urolithin A
• Article: Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents
• Potential anti-aging benefits
• Thesis: How can we unlock the power of microbes or bacteria to confer benefits to their human hosts

-How probiotics affect males and females differently...52:35

• Women have a longer digestive tract than men, which leads to more issues with the digestive system
• Females could benefit from a folate producer in their gut during pregnancy; would be out of place in a male
• Environment, diet are of far more significance than gender

-Raja's take on companies who recommend particular probiotic strains to consume based on tests of the gut and microbiome...56:10

• Still no consensus on what determines a healthy microbiome
• Recommending a particular product based on test results is problematic
• Genus vs. species vs. strain recommendations; the more specific the better results
• "Relative abundance" vs. "absolute abundance"
• Better approach: take specific strains identified to treat specific issues
• Stratification, personalized approach, is not the optimal goal
• The gold standard is a microbe that is applicable to the entire human (or mammal) population and has reproducible effects
• To conclude: There are some good things about microbiome tests; however, use caution when they recommend certain products based on the test results

-Whether personalized microbiome testing will allow people to target a probiotic species for their specific gut profile...1:03:00

• Yes, but it will not look anything like the probiotics that are on the market today
• Some organisms won't grow if other like organisms are not in the mixed community
• The gut is an ecosystem; ecosystem theory comes into play
• Diversity and seasonality of plants rich in phytonutrients and high fiber foods

-The importance of the CFU (colony forming unit) of a probiotic...1:10:24

• Depends on the study and the trial
• Shotgun approach: inject high density of organisms into the gut and hope for the best
• Before you take any probiotic...
  • Ask the company to show the studies on their strains
  • Have they been studied in a human population
  • And for what end points

-What Raja is most excited about with his work...1:18:10

• Get 15% off your first order from SEED when you use discount code: GREEN15

-And much more... Resources from this episode:

-SEED Male Probiotic formula. Click here and use discount code: GREEN15 -SEED Female Probiotic formula. Click here and use discount code: GREEN15 -Probiotics: Reiterating What They Are & What They Are Not -Documentary: "Missing Microbes" -Urolithin-A -Article: Human gut study questions probiotic health benefits -Article: Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents

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Do you have questions, thoughts or feedback for Raja or me? Leave your comments below and one of us will reply!

 

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