Commercial probiotics have received some bad press lately, some of it deserved. This is not to say that probiotics, single-species or multiple-species, are useless—they are not, as I discussed in my criticisms of the recent episode of 60 Minutes in which Dr. Jon LaPook delivered a narrow, one-sided criticism of probiotics.
Current commercial probiotic products have some serious shortcomings. Among them are:
- The failure to specify bacterial strain—Strain specificity is crucial. You have E. coli; I have E. coli. Eat lettuce contaminated with E. coli from cow manure and you can die—same species, different strain. Likewise, the GG strain of Lactobacillus rhamnosus has been shown to reduce diarrhea associated with antibiotics, an effect not shared by other strains of L. rhamnosus. But, pay something like $50 for a probiotic product containing L. rhamnosus—no strain specified, a major problem. Or how about L. reuteri? We know that the DSM 17938 and ATCC PTA 6475 (yes: strain designations are wildly out of control, with some probiotic manufacturers even assigning their own proprietary strain designations that make it even tougher to know what strain is present) strains are effective for generating many of the age-reversing effects that we have been enjoying in our L. reuteri yogurt. It means that the L. reuteri in a probiotic, strain unspecified, may or may not mimic these effects—you simply cannot know. In four studies of Lactobacillus lactis given to premature infants at risk for a devastating condition called necrotizing enterocolitis (NEC), in which a part of the bowel actually dies, strain was specified in only one study; in this study, the Bb12 strain proved ineffective, while in two of the other studies an effect in reducing NEC was shown, no strain specified. You can predict that it is therefore impossible to know if the probiotic you use exerts beneficial effects or not. It is not uncommon for formulators of commercial probiotics to choose strains based on availability and cost, not on efficacy. You cannot therefore know whether the commercial probiotic product you bought achieves the effect you desire.
- Failure to include “keystone” species—Now this is not entirely the fault of probiotic manufacturers, as some keystone species (and strains)—i.e., species that, by their presence and metabolic activity, support the growth of other bacterial species—cannot survive the encapsulation process and remain shelf-stable. Akkermansia muciniphila, for instance, is a keystone species whose presence and activity help cultivate many other desirable species, but is not readily encapsulated. (A European group, however, claims to have circumvented this process and say that they should have a commercial preparation sometime in future.)
- Failure to factor in bacterial species/strain interdependency—In other words, it may not only be a matter of species and strain, but also of groups or microbial species/strains that “rely” on each other and are interdependent, an issue related to the keystone species concept. It might turn out, for example, that L. reuteri strains have greater effect when B. infantis and Akkermansia muciniphila and their metabolites are present.
- Failure to couple specific prebiotic fibers with specific species—Some species “prefer” long-chain fructooligosacharides (FOS), i.e., inulin, while others prefer the shorter-chain FOS, while others prefer galactooligosaccharides or isomaltooligosaccharides, polyphenols, pectin, etc. We can therefore “bloom” species/strains or groups with prebiotic fiber choice.
As if this couldn’t get any more complex, the effects of a specific bacterial species/strain also varies depending on the consumer’s diet, other exogenous factors influencing bowel flora composition, and integrity of the mucus lining. Someone following a strict ketogenic diet, for instance, who has caused Akkermansia muciniphila and Parabacteroides merdae to over proliferate and consume the mucus lining that sets the stage for intestinal inflammation and endotoxemia will have a very different experience with a probiotic than someone who is a vegetarian loaded with Prevotella species.
Yes, modern commercial probiotics are generally unsatisfactory with a few shining exceptions such as the L. reuteri strains we use to make yogurt, L. rhamnosus GG and Saccharomyces boulardii that abbreviate post-antibiotic diarrhea, commercial Bio-K species/strains (Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2) that reduces risk for C. diff enterocolitis, and a few others.
Probiotics are a work in progress. I predict that the commercial probiotics of, say, 2025 or 2030 will look entirely different than those in 2020, as the science is evolving at breakneck speed. In the meantime, we shall be working on crafting a a probiotic preparation that puts these concepts into action based on the best evidence.
What is your opinion of the spore based probiotics that Kiran Krishnan espouses? He speaks of the importance of keystone strains to balance the microbiome.
Pajenn65 wrote: «What is your opinion of the spore based probiotics that Kiran Krishnan espouses?»
I don’t recall Dr. Davis addressing that product line per se. Just checking the Inner Circle site:
Saccharomyces boulardii — is discussed in the Advanced Topic on SIFO.
Bacillus coagulans — is under active investigation (as B.c. GBI-30, 6086). Strain matters, and I’m not sure what B.c. HC™ might be.
Bacillus clausii — No program remarks so far.
Bacillus subtilis HU58™ — “likely beneficial”, but again, strains matter.
Taking a broader brand view: not sure the Probiogen formulators know what they are doing. Just looking at the “Adults 55+” product, I spy:
⚠ 1200 mg Ca (as calcium carbonate)
⚠ Folate (B-9) in the folic acid form (vs. methylfolate)
⚠ B-12 in the cyanocobalamin form (vs. methylcobalamin)
⚠ Maltodextrin filler
re: «He speaks of the importance of keystone strains to balance the microbiome.»
Indeed, and the question remains open as to what those might be.
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Bob,
Thanks for your comments.
Dr Davis has got me interested in the microbiome – I have been making the L. reuteri “yogurt” since his initial post – and in my search for more and more information, I came across an article about Kiran Krishnan. He is a research microbiologist and, from my lay perspective, appears to have an incredible insight into the microbiome. I have searched for podcasts with him on and, notwithstanding that he is selling these probiotics, he seems to have some science behind his claims, one of which is that most probiotics do not survive passing through the gastric barrier. It is only spore based probiotics that survive this. He has done some experiments/tests with amazing outcomes for all matter of illnesses..
With the work done by Dr Davis and the apparent fascination that he has in this area, it would be fantastic to get them both in a room to discuss their thoughts. I was hoping maybe Dr D had come across him in his travels.
It really is the new frontier.
Thanks again.
Pajenn65 wrote: «With the work done by Dr Davis and the apparent fascination that he has in this area, it would be fantastic to get them both in a room to discuss their thoughts. I was hoping maybe Dr D had come across him in his travels.»
It might be Dr.D’s top interest at the moment, and I suspect he is aware of, if not actually in contact with, all the key people with insight into…
re: «It really is the new frontier.»
Absolutely, and it can’t even be taught in med school yet, because too many important questions have no answers (plus, med schools are still oblivious to nutrition, for which answers do exist, and which is at the root of 80% of sickcare expenses today).
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I just finished reading for the second time the latest edition of wheat belly. One question i have, where is gout in terms of wheat? I was able to read about almost every auto-immune disease but, not a single time was gout or high uric levels mentioned in the book? just curious if this has any relationship to wheat.
George Hanna wrote: «…where is gout in terms of wheat?»
The program presently has no specific protocol for that. Allopurinol, if you are using it, is seen as a relatively benign agent, and (for someone following the program), anti-inflammatories might have net benefit.
To add some personal speculation, anyone with gout must avoid fructose, which is upstream in the uric acid pathway. Anyone doing any very low net carb diet (such as WB/Undoctored) is not likely to be at high exposure to fructose as a mono-saccharide, or other simple saccharides (like sucrose) that contain it.
But there is a sneak path, and that’s where grains come in. There exist gut bacteria that either express fructanases, or can otherwise convert fructans to fructose in the gut, which is then directly absorbed as fructose. According to sugar researcher Richard J. Johnson, anyone who is obese is at much higher risk of harboring these species.
Fructans are prebiotic fiber, and include FOS (fructo-oligosaccharides, such as inulin), normally beneficial. Wheat is loaded with fructan (it’s the #1 dietary source of fructan for people on standard diets). So the top thing the program would have in the way of advice to anyone with gout, is also the first thing that’s advised to everyone.
The next thing would be to consider would be SIBO, because you don’t actually need to be obese to have an overgrowth of the adverse bacteria. Anyone having chronic problem with dental caries, for example, likely has at least one of the strains involved.
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Thank you so much for your kind reply. Just one thing that Allopurinol is a benign agent. It’s anything but benign after 11 years using it. I will not wish anyone use Allopurinol. Yes, the early years using it were wonderful, it’s after 8 plus years that the problems start. I think gout is the early marker for many health ailments.
Have Dr Davis been able to identify an old heirloom grain that is similar to the early wheat grains of old. That will be interesting to see if someone is experimenting with this.
George Hanna wrote: «Have Dr Davis been able to identify an old heirloom grain that is similar to the early wheat grains of old. That will be interesting to see if someone is experimenting with this.»
Heirloom grain? is an FAQ here, and the answer basically is:
consume heirloom grains — contract heirloom ailments.
On the blog: What happened to the first wheat eaters?
I think my household still has an unfinished bag of einkorn flour from our early ‘denial stage’ days.
So as you know, the program approach to gout, to the extent that it has one, is:
• do the core program
• go low purine as needed
• allopurinol as needed
and if I had it, I’d definitely want to be checked for intestinal bacteria that express fructanases.
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Great article. “In four studies of Lactobacillus lactis…” Did you mean Bifidobacterium Lactis?