Those of you following these conversations in the blog know that information on the microbiome and its practical application to human health is exploding. A day doesn’t pass by when something novel and interesting comes our way that has the potential to provide important new insights into human health.

But there is a glaring lack of knowledge in one specific area: dose-response, i.e., the result you obtain at different “doses,” or numbers of microbes ingested as probiotics. While it is among the most neglected areas in microbiome research, it is also a path of enormous promise. There is a lack of data on dose-response mostly due to budgetary limitations: it is very expensive to conduct such studies that compare differing doses, then measure end-effects. Dose-response measures are the rule in the pharmaceutical world, an industry with virtually unlimited resources. Most of the labs that perform microbiome research do not have such resources.

Here’s a recent study of Lactobacillus gasseri BNR-17 in which the research group made the unusual attempt to decipher dose-response. Ninety overweight or obese participants were given placebo, “low-dose” L. gasseri one billion CFUs per day, or “high-dose” L. gasseri of 10 billion CFUs per day over 90 days. Participants were also asked to reduce calorie intake slightly while also modestly increasing physical activity. While the placebo and low-dose group experienced no reduction in waist circumference, the high-dose group experienced 5.0 cm reduction in waist circumference, 21.6 cm² reduction in cross-sectional area of abdominal visceral fat by CT scan.

Think about this: A one billion CFU dose per day had no significant effect, a dose commonly used in commercial probiotics. The ten billion CFU dose per day had a substantial effect—a 5 cm reduction in waist circumference is huge. They called a ten billion dose “high,” but I would have called it “slightly more but still low-dose” because those of us using my method of prolonged fermentation are playing around with hundreds of billions, typically 300 billion CFUs per 1/2-cup serving of our L. reuteri yogurt. What would 100 billion CFUs per day of L. gasseri have accomplished? 500 billion? 1000 billion (a trillion)? My bet is that the effects would have been even greater. Adding three additional arms to the study to assess the effects of higher doses would increase study costs substantially, typically making such efforts out of reach for most groups performing microbiome research.

By the way, we are very careful around here regarding bacterial strains, i.e., some effects of microbes may be unique to only some strains and not all strains within a species. My favorite example is E. coli, a species most of us harbor in our gut microbiomes. But get exposed to some E. coli strains from lettuce contaminated by cow manure and you can die from exposure to that strain—same species, different strain. However, having examined much of the efforts to characterize various strains of L. gasseri beyond BNR-17, I predict that the body composition-modifying effects are species-specific, i.e, it may be shared by other members of the species. There are similar data on reduction of waist circumference, for example, with the 2055 strain of L. gasseri.

Regardless, we’ve got to start thinking about dose-response. In the meantime, if you are fermenting your microbes, whether it’s L. reuteri in our extended fermentation “yogurt,” or  L. gasseri as yogurt, or L. plantarum and Leuconostoc mesenteroides in fermented veggies, or Saccharomyces bourlardii in our sparkling juices, know that you are exploring the effects of much higher “doses” of probiotic microbes.