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Ben Greenfield's discoveries, from the latest news on the fronts of fitness, nutrition, health, wellness, biohacking, and anti-aging research. I also recap my upcoming events and special announcements so you can keep up with giveaways, discounts, and more!
New Discoveries Of The Week: Cool New Things I'm Trying, Books I'm Reading, And More!
What I've Learned Lately About Probiotics
If you listened to my fascinating episode with Joel Greene (Part 1 here & Part 2 here), then you may have heard some controversial information regarding probiotic supplementation. This interested me quite a bit, since I actually use the SEED Synbiotic daily and Joel seemed to imply that it may cause brain fog and may not adequately heal gut lining—and also expressed a few other concerns that compelled me to get some counsel from my brilliant bacteria friend at SEED, Raja Dhir, who you first met in Dangerous Probiotic Myths, The Probiotic Ben Greenfield Uses, Anti-Aging Effects Of Probiotics, Should Males Vs. Females Take Different Probiotics & Much More.
Here's what he had to say:
Q: Can probiotics cause brain fog. What’s your read on that?
The brain fog paper cited regarding probiotics has a lot of issues. We published a paper in Frontiers in Microbiology last year directly responding to the limitations of the study:
Another pertinent example of the over-interpretation of limited data is a recent study conducted on 34 patients suffering from “brain fogginess,” which is a set of presentations including impaired concentration, confusion, and poor short-term memory. Based on the observation that consumption of fermented food or commercially available microbial products was a shared trait amongst the patients reporting brain fog, the study implied that all probiotics could be causative agents of brain fogginess. While the definition of probiotics accommodates strains of any taxa, it is unlikely that these included the Streptococcus, Staphylococcus, Neisseria, or Hemophilus, which were the primary organisms detected by culture in the duodenal aspirates. Furthermore, 68% of the cohort presented with small intestinal bacterial overgrowth (SIBO), and there were no data to verify patients were acidotic; a crucial linkage considering many lactobacilli and all bifidobacteria only produce l-lactate and not d-lactate. In the future, appropriate trial design can strengthen the field by moving away from observational and correlative data sets. In this case, the study concluded that probiotics may be causative of brain fog on the observation that antibiotic therapy alleviated symptoms of brain fog, whereas a more appropriately designed study would have split the patients after antibiotic therapy into two groups, and upon reintroduction of probiotics in a defined cohort, compared the emergence of symptoms against the antibiotic-treated control.
Q: Regarding gut barrier function, what are your thoughts about pectin and the possibilities there for tight junction integrity?
Epithelial tight junction integrity is important in gut homeostasis. More than pectin, or any polyphenolic compound, L-glutamine is the most potent regulator in the preservation of gut barrier function. The gut mucosa is the major site of glutamine metabolism and glutamine is the preferred fuel for enterocytes and colonocytes. We've interrogated tight junction protein expression pretty heavily, and single strain, as well as consortia of probiotic bacteria, can increase tight junction protein expression. Not all bacteria do this, and we had to screen our strain bank extensively to find a consortia that does. Another good study showed this too and found that a human origin probiotic cocktail increased short-chain fatty acid production, which is widely protective for the host as shown here (immunological / T cells) and here and here (gut-brain axis).
Q: How important is butyrate?
I like that you guys hit on butyrate and its role in host metabolism, especially when it's a metabolite of microbial cross-feeding vs. isolated. Bifidobacteria (not all) produce lactate and some produce acetate, which is used by Akkermansia and friends (part of the Clostridia cluster XIVa) to produce butyrate. Earlier this year we generated data showing that after exposure to antibiotics and ethanol (vodka), our Daily Synbiotic cocktail ‘rescues' short-chain fatty acid production, resulting specifically in a net increase in butyrate production compared to control (naive recovery). Even more striking we showed that it increases butyrate production to higher levels than the original baseline microbiome prior to the challenge.
Q: What about bacteria associated with weight maintenance?
Akkermansia is a cool bug—we know the scientist who really put it on the map (Dr. Patrice Cani). But it's not so simple to associate its presence in lean people/mice models with health. A big debate we had at the Keystone Conference last year was around why it's there in lean people, but elevated in the gut of patients with neurodegenerative disease. It has a lot of promise but we need to be careful about associations. It's also present in Japanese women, but virtually nonexistent in Japanese men, so there's more to the story than focusing on a single bug as a marker for microbiota mediated metabolism.
Human evidence for polyphenols in stimulating Akkermansia hasn't been sufficient to date. This is from one of the papers he cites:
As far as the functionality of polyphenols has been deemed to contribute to the strong antioxidant effect observed in in vitro experiments, recent results have indicated that relatively poorly absorptive polyphenols directly affect intestinal bacteria and show the possibility that the antioxidant effect is mediated by so-called “good bacteria” such as Akkermansia. However, polyphenols have not been sufficiently analyzed in human subjects, and the evidence for its involvement in increasing the abundance of Akkermansia has not been sufficient.
We can't find evidence to support that cold exposure affects Akkermansia. We’re big fans of both sauna and cold plunges but can't find the link. Also, Inuit diet hasn't been shown to affect Akkermansia:
No effect of the Inuit diet on strain diversity was observed within either Akkermansia or Bacteroides (Mann-Whitney test).
Q: Any thoughts on fiber and the carnivore diet?
The podcast discussed TNF-a and intestinal inflammation blunting the protective effects of fiber. In general, we agree with the sentiment that carnivore/fiber elimination probably helps people that have upstream intestinal issues rather than being net-positive at the population level. A group at UCSD has shown that probiotics can blunt the effects of TNF-a (and IFN-g) on epithelial function.
Overall we agree with looking at the gut as a system and enjoyed the thought experiment around ‘rebuilding' the gut, but based on the evidence, there is no indication that “probiotics” as a category are bad or that they don’t work. The issue is that not all, or even many, commercially available products have data on any of the points discussed above, which is why looking at the strain(s) and desired outcomes is critical when discussing probiotics in the context of gut microbiota, and why consumers should ask these questions of any probiotic product they take.
So, ultimately, I don't plan on halting my daily intake of 3 SEED Synbiotic capsules. I truly think SEED makes one of the best probiotics out there.
What separates SEED from other probiotics? It is comprised of 24 strains characterized at academic institutions and research partners in Italy, Spain, Belgium, the US, and Japan. Twenty-three of the strains are human-derived and one strain was isolated from fruit (screened against 400+ strains of the same species) specifically because it has clinically demonstrated the ability to help promote healthy cholesterol levels. The benefits have been validated in 16 strain-specific, double-blind, placebo-controlled, published human studies as well as 13 in vitro/ex vivo mechanistic studies.
Bacteria are fragile—they are sensitive to light, temperature, and moisture. In many cases, they hardly survive the trip from manufacturer to store shelf, much less your digestive process (think stomach acids and bile). SEED took care of this. Their nested capsule technology ensures bacteria stay alive and viable through digestion and make it to your colon, where their work begins. They use an algae delivery system to provide additional protection for the most sensitive strains. This also means there’s no synthetic or chemical coating, and that it is shelf-stable for 18 months and requires no refrigeration!
If you want to try SEED for yourself, you can click here and use code BEN15 to save 15%.
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