Of Probiotics Strain-Specificity

What’s a species, what’s a strain, why it matters

In the probiotics sector, there is a consensus that products should label the microorganisms they contain down to the strain level. The International Probiotics Association (IPA) writes it clearly in its labelling infographic, as does the International Scientific Association for Probiotics and Prebiotics (ISAPP).

However, a report by Lumina Intelligence highlighted that two thirds of probiotic supplements on the market still fail to report bacteria down to the strain level. That says we need to talk about this.

What’s a species, what’s a strain?

Let’s start from something familiar. You. Your species is Homo sapiens. OMG, that’s my species too! We have something in common! Genetic traits, epigenetic traits, we’re (physiologically) omnivores, we probably can both read, write, drive and so on. But we’re two different individuals with our own sets of specific competencies and preferences. I love spinach and praliné, I like to speak and write about probiotics and poop, I sell bacteria for a living. What about you?

The example in the picture above is even better. A chihuahua and a German Mastiff are both Canis lupus (yes, the chihuahua is a long journey from his wolf ancestor) but they present massive differences in their appearance and abilities.

With regards to bacteria, it is the same. Take the species Escherichia coli. It exists in different strains: E. coli 0157:H7 for example is notorious for its virulence and the deadly gut hemorragies it can cause. E. coli Nissle 1917 is a probiotic registered as a drug in several countries. It opposes symptoms of inflammatory bowel diseases (IBD).

How close do you need to be to belong to the same species?

Premise: life is a continuum, and the need to seperate and distinguish species from one another depends more on the human mind’s comfort in categorizing than on the intrinsic differences between species. You could put the cut-off wherever, it is arbitrary. But we created language to put a meaning behind words so we can understand each other, thus taxonomists (whose job it is to categorize and organize the living realm) created rules to distinguish species.

In 2019, the international bacterial taxonomy committees considered two different bacterial isolates as pertaining to the same species on the basis of DNA hybridization (DDH) percentage equal or greater to 70% — which corresponds to 98.2–99.0% 16s rRNA similarity.

Please don’t ask me the level of similarity expected among a same strain. There is always variability, and microorganisms exist in their natural environment only in a dynamic state of being. They accumulate mutations, they exchange plasmids, they are different from a moment to the next. So when does the difference accumulation imply it’s become a different strain? If you know, please do tell me.

Side note about genus (the group directly over species): With more and more new isolates identified and described, the genus Lactobacillus grew to over 200 different species which shared only 65% nucleotide identity. Bacteria were grouped together when they were as different as a man is from a mouse lemur! This had become too much variability to belong to a same genus, so taxonomists split Lactobacillus into 23 new genera in April 2020. And now the species that was referred to as Lactobacillus plantarum, for example, is renamed Lactiplantibacillus plantarum.

Why is it important to label the strain?

The safety (for non-QPS strains such as E. coli) and health benefits of probiotics are strain-specific. The example of E. coli is extreme, they are as distinct as life and death. For other species, the difference is usually not as profound, but it can mean the distance between effective for the purpose, and ineffective.

For example, a study compared a blend of 8 different strains to a blend of 8 other strains from the exact same species in the exact same proportion. The efficacy in colitis in mice was observed only with one of the blends. Similarly, different strains of the same species don’t exert the same immunomodulatory activity. If you’re taking a probiotic for atopy, or for inflammatory disorders like IBS for example without selecting the strain, you could be taking an excellent probiotic studied for doing the exact opposite of what you want.

Good manufacturers should always label the strain on their products: it is the only way for prescribers and consumers to do their own research through Google Scholar and Pubmed for the best product, demonstrated effective for the benefits they look for.

Conclusion

It is important to acknowledge that strains among the same species do share some traits — this is why and how we identify them among the same species. That’s also why the European Food Safety Agency (EFSA) gave a positive advice for the one claim that’s authorized in Europe at the species level: the cultures in yogurt (Lactobacillus bulgaricus and Streptococcus thermophilus) support the digestion of lactose. Yes, their ability to digest lactose is represented across the species. But it’s not always the case for the benefits you’ll look for. And the more we understand about the mechanism of action behind the properties we select for, the more we’ll be able to define if the trait is shared, and anticipate efficacy even before it is confirmed in the clinical setting.

So next time you develop a probiotic, launch one, or pick one up at the store, remember: would you adopt a chihuahua if you needed a watchdog?