What is the ideal dose of L. reuteri?

From Abuqwider et al 2022 via Creative Common License 4.0:
https://pmc.ncbi.nlm.nih.gov/articles/PMC8953724/

What is the ideal dose of L. reuteri? Short answer: We don’t know. So what DO we know?

First of all, microbes are not drugs nor nutrients. Take a drug and you need to be aware of half-life, duration of action, how the body clears the drug via liver metabolism or kidney clearance. Likewise, a nutrient such as riboflavin or vitamin D follows similar pathways of generating effects, metabolism, and clearance. Microbes are subject to none of these factors but instead either take up residence or pass through the gastrointestinal (GI) tract, and they can proliferate or reproduce within the GI tract, phenomena that differ with each species. We therefore need to follow different “rules” when it comes to microbes.

We also know that microbial numbers in the hundreds of millions have effects on infants but such low numbers have minimal effects on adults. This came out of the several dozen studies conducted using doses of 100 million of L. reuteri and other species. Yes, doses in this range may reduce colic and post-antibiotic diarrhea in a one year-old child, but yields almost nothing in a fully grown adult. So low doses of <1 billion per day seem to yield little to no benefit for most of us.

We also know that our “yogurt”-making experience yields 300 billion microbial counts (CFU’s) per ½-cup or 120 ml serving, as evidenced by repeated flow cytometric assays. This high dose yields significant benefits in multiple aspects of health and functioning. We obtain such extraordinarily high counts, of course, by using my methods of prolonged fermentation combined with addition of prebiotic fiber, an inexpensive and accessible way to tremendously increase microbial counts. (Recall that, by the FDA’s definition of yogurt, we are not making yogurt but something that looks and smells like yogurt but is entirely different from the products you buy in stores or make using conventional methods.)

So it appears that the ideal daily dose of L. reuteri is somewhere between the 100 million infant dose and the 300 billion “yogurt” dose, a spread that is 3000-fold wide. Say you wanted to obtain your daily intake of L. reuteri as a probiotic capsule, rather than the hassle of making the “yogurt”—how many microbes do you need to ingest? I don’t know the precise number but. as experience grows playing with varying intakes of the microbe, my gut sense is that the truly effective dose is somewhere between 40 and 100 billion CFUs per day. If I was in the pharmaceutical industry and had billions of research dollars to spend, we would figure this out in short order with a series of dose-response studies. Alas, I don’t rip people off for billions of dollars to fund studies and therefore work with far more modest budgets. But I believe that intakes in this 40-100 billion per day range seem to yield all the effects we desire.

If L. reuteri and other probiotic species were able to take up permanent residence in the GI tract, then dose would likely not matter, as microbes are capable of proliferating in the GI environment. This would be true, for instance, if your mother passed L. reuteri or other species onto you at birth with passage through the birth canal, breastfeeding, and contact. But repeated studies have shown that, if obtained as a probiotic, a species like L. reuteri persists for no more than two weeks, with numbers dropping off sharply within days of consumption. Why the difference? No one knows, but many of us speculate that it depends on the microbial milieu, i.e., the context or microbial species present. Perhaps it will be shown in future that, in order for L. reuteri to take up permanent residence, a dozen other microbial species are required for cross-feeding supportive effects. If true, no one currently knows what the community, or “consortium,” of microbes should consist of, so we are presently left with only temporary residence for L. reuteri and other probiotic species.

There are additional complexities that increase our uncertainty on dosing. What about the microbial milieu that L. reuteri is being added to: Could species like E. coli and Klebsiella in your duodenum and jejunum impact its effects? What if you lack species such as Eubacteria and Clostridia that might support the metabolism and effects of L. reuteri? Do you harbor genetic variants such as oxytocin receptor variants or endocannabinoid gene variants that modify your L. reuteri experience? You can appreciate that, while we know a lot about L. reuteri, there is a lot we have yet to learn.

The original IHB post is currently found on the: ⎆Infinite Health Blog, but accessing it there can require an unnecessary separate blog membership. The copy of it above is complete, and has been re-curated and enhanced for the Inner Circle membership.