Thursday, April 27, 2017

The Emerging Understanding of Probiotics and Colonization

Recently I was asked a good question by a doctor about oral probiotic supplements and whether they survive transit in the GI, particularly very acidic stomachs, and whether or not there are studies confirming colonization of various probiotics strains.  Since this question represents the more widespread thought process of probiotics -- a thought process that is becoming antiquated -- I thought I would pass the answer on.

To answer this question, let's consider the strain studied in weight control.  The genus, species, and strain are: B. Lactis B420.  B420 is not a human-strain. It was first identified in dairy. However, as fermented dairy foods are common in human diets, B420 can be grown from a stool sample from non-supplemented humans (proof of survival in GI transit). Also, in the current study, B420 was cultured from stool samples of the treatment arms as proof of survival in GI transit. So is this same culturing required for all human-strain probiotics? Not really. If they are human-strains, how did they get there in the first place? Orally, through foods, through the gut. Non-protected, no 'encapsulation' was needed naturally. And one would assume that this is the case even with very low pH (high acidity), since probiotics from fermented foods appear to still colonize the guts of people in all pH ranges.  (i.e. People with very high acid stomachs with a pH of, say, 1 or 2, do not have sterile GI tracts.  They are still colonized with all kinds of bugs.)

Regarding survivability of stomach acid, then, what is well understood is that the stomach is acidic pretty much all the time (while food may actually act as an acid buffer), and that human-strain probiotics should 'naturally' be able to survive GI transit (i.e. how did they get their in the first place?).

Now, here's the biggie: 

It used to be thought that the rationale for use of oral probiotics was to repopulate the gut. That is out of date. The current understanding of probiotics is strain-specific activity. In other words, residency in the gut microbiota seemed to be the marker of a strain's hardiness/survivability in times past.  But not anymore. The modern understanding is that oral probiotics are not about colonization.  Oral probiotics are about their transient effects, helping to make the neighborhood a better place. A healthy gut is a diverse one, made up of hundreds, even thousands of species. How can one create diversity through oral probiotics of one, two, or even eight strains? It likely cannot be accomplished with so few strains.  The oral probiotic stays for a little while, does its job, and then leaves.  Job done.  

Part of the definition of oral probiotics​ is proven efficacy in humans proven by reams of research, which, by the way, is why you want the genus, species, AND strain -- all three -- identified so that you can correlate the strain with the research.  Said another way, according to sources like the International Scientific Association of Prebiotics and Probiotics, a TRUE probiotic must have two things in particular in order to be legitimately called a probiotic: 1) genus, species, and strain identified, and 2) they must have proven oral benefit - including survival through the GI tract. If a product simply says on the label, for example, lactobacillus acidophilus, but no strain, then you cannot connect it to specific research, and thus, you don't know if it survives digestion or not, and you don't know what, if any, benefit it has in humans.  A product without the strain identified can probably rightly be called a bacteria, but NOT a probiotic.  If the strain is not identified on the label it is absolutely impossible to make any claim of being orally effective

Typically, part of the evaluation of a probiotic is observation of its traits (phenotype). The probiotic strain is tested for acid and bile tolerance. If tolerant, this is recorded. Once understood it is no longer necessary to test each generation of this proven strain trait. What is necessary is to test the DNA to ensure that each generation is the same as previous (genotype). 

The third factor to GI survival is the use of human microflora. As stated above, these species/strains ‘natively’ survive passage through the GI tract,​ as this is their normal abode. Once againhow do the hundreds of species of good flora get to the gut in the first place? Nearly a​ll orally. Ninety-percent of the bacteria that enters the body does so through the mouth. ​The genus/species of bacteria that live in our gut survive and thrive,​ as they are inherently adapted to do. 

As an example, consider the genus and species of one common probiotic family, Lactobacillus acidophilus.The latter term, acidophilus, is​ from the Latin, and refers to ​"acid-​loving."​
So, in short, yes, most probiotics survive digestion (some strains much better than others), even in very acidic stomachs.  And yes, part of the research in identifying a true probiotic is its effectiveness in humans. But again, colonization is not the true marker of a probiotic's effectiveness: strain-specific activity is.  And that is another reason why the genus, species, and strain listed on the bottle is so important.

In closing, I should add that some companies choose to list the strain in their promotional literature, but not on the bottles.  This, too, is a quality issue because by not listing it on the label of each bottle, companies don't have to prove that the strains are in THAT bottle or lot.  Companies who do random batch assays and then list the strains in their promotional literature are not proving anything in regards to all the different batches and bottles.  If a company lists the strains on the bottle, however, they have bound themselves to being able to provide documentation of the presence of those strains in that bottle and batch.