How Probiotic Gut Bacteria Use Bile Acids to Modulate the Biome

How many times on this blog have I exclaimed over the incredible complexity of the human biome?  I am frequently asked by readers questions like, “What prebiotic do you recommend for [enter medical condition here]?” and I write back that I honestly have NO idea, because science as yet has no idea.  There is not a one-to-one correspondence between pretty much anything in the biome:  you don’t do X to obtain Y results, because there are a million other factors that need to be considered.

A recent paper out of North Carolina State University provides yet another excellent example of this complexity.[i]  These researchers were studying how probiotic bacteria manipulate bile acids to promote their own survival – and to squash the pathogenic competition.  For obvious reasons, this is a pretty important subject:  if we could learn how to use the body’s own defenses to boost biome health and to kill pathogens, it would be an awfully good thing!

As you know from previous posts, bile acids, which are produced in the liver (and stored in the gallbladder) are extremely important for both digestion and gut health, in that they modulate the gut flora.  As they are released into the intestines when you eat, they are modified (often by taurine or glycine) into something called a conjugated bile acid.  Some kinds of gut bacteria have enzymes called bile salt hydrolases (BSHs) which can deconjugate the taurine or glycine which allows other bacteria further down the intestine a chance to utilize them.  These conjugation/deconjugation processes change the toxicity of the bile acids which then affect various gut bacteria:  some survive better, others are killed off.

Prior to this new research, it was believed that probiotic bacteria deconjugate the bile acids, making them less toxic, so that bacteria can better survive…but, as one of the co-authors of the paper says, “…the reality is a lot more complex — these enzymes are more specific than we thought. Depending on which BSH is there and which bile acid it acts on, you can shape the gut in different ways, making it more or less hospitable to bacteria or pathogens.”[ii]

To further elucidate these incredibly complex processes, they ran both in vitro and in vivo experiments.  They looked at how two strains of Lactobacillus grew in the presence of different bile acids and found that conjugated glycine and taurine played a major role in determining toxicity of bile acids, as I mentioned above.  They then isolated the BSH enzymes to study how active they were on specific bile salts and whether or not they could affect the survival of Lactobacilli.

Their results, simply put:  the toxicity of bile acids to bacteria was not only dependent on whether or not the bile acid was conjugated or not conjugated but also upon both the kind of bacteria involved and the type of bile acid itself.  This, the paper states, is essentially why using BSH enzymes to promote the colonization of probiotics and to treat high cholesterol or obesity has failed.  Again, there is no one-to-one correspondence:  I give THIS BSH enzyme to get THAT effect.  The paper concludes, “Our findings have provided a foundational understanding of how BSHs equip probiotic lactobacilli to deal with BA [bile acid] stress. Future studies are needed to elucidate the role of BSHs in adapting Lactobacillus and other gut commensals to the competitive environment within the microbiota, and similarly how BSH activity alters the structure and function of that ecosystem.”

One of the researchers summarizes all this beautifully:  “If we’re going to try and design the gut microbiota in the future, we really have to understand all the players — bacteria, enzymes and bile acids — and their situational relationships.”  Kind of makes your head spin, right?

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[i] Matthew H. Foley, Sarah O’Flaherty, Garrison Allen, Alissa J. Rivera, Allison K. Stewart, Rodolphe Barrangou, Casey M. Theriot. Lactobacillus bile salt hydrolase substrate specificity governs bacterial fitness and host colonization. Proceedings of the National Academy of Sciences, 2021; 118 (6): e2017709118 DOI: 10.1073/pnas.2017709118

[ii] https://www.sciencedaily.com/releases/2021/02/210201170610.htm