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.