Therapeutic Microbes and Their Metabolites

Therapeutic Microbes and Their Metabolites

Probiotics, Prebiotics, and more…

Probiotics have become so popular that you can find them pretty much everywhere, from big box stores to gas stations. Defined as live bacteria administered to provide health benefits,1 probiotics are in food, supplements, and beauty products. Research suggests that probiotics can help your metabolism, improve your mood, and may even help you fight infections.2-4 The popularity of probiotics has led to a whole new class of microbiome-related supplements including therapeutic microbes, the nutrients that feed them, and the metabolites they produce.

Initially, supplement and food companies were trying to figure out what was needed to keep probiotics alive. These food components that microbes digest are called “Prebiotics.”5 Companies that sold probiotics would include dietary fiber in the capsule to help keep the probiotics alive on the shelf. People eventually realized that the same foods keeping probiotics alive were also good for feeding our gut microorganisms too. Thus evolved the world of prebiotics.

Historically, prebiotics were limited to dietary fiber. Research now shows a number of prebiotic molecules in our diet that microbes can digest including fructans, galacto-oligosaccharides, starch and glucose-derived oligosaccharides, a variety of other oligosaccharides, beta-glucans, some culinary spices, and flavanols.5 The foods shown to have the highest prebiotic potential include chicory, onion, Jerusalem artichoke, banana, and asparagus. Beta glucans add mushrooms, yeast, and algae to the prebiotic category, and recently, culinary spices and chocolate were also shown to have prebiotic potential.

The World of Therapeutic Microbes has Expanded Beyond Probiotics

Probiotics have been further manipulated to create new categories. For example, parabiotics are heat-killed probiotics. (The parabiotic name isn’t official yet.) You may wonder why we would heat-kill probiotics. It turns out that heating probiotics is like putting them in the sauna. They sweat out all sorts of new metabolites that they don’t make when they aren’t heat stressed, and these metabolites promote health when administered. For example, heat killed Lactobacillus rhamnosus was shown to heal intestinal permeability in a mouse model of colitis.11

It turns out that heating probiotics is like putting them in the sauna. They sweat out all sorts of new metabolites that they don’t make when they aren’t heat stressed, and these metabolites promote health when administered.

Functional definitions of probiotics are also emerging. Psychobiotics are a category of probiotics that have been shown to impact mood.12 It’s exciting to have a category of microbes that could help with depression and other mood disorders. As we know that some commensal bacteria can produce neurotransmitters such as serotonin and dopamine, it’s not a huge surprise that probiotics may also produce these substances and others that impact mood.3,12,13

Learning how to feed microbes and keep them alive was just the first step, now science is recognizing the potential significance of the end products of microbial metabolism. This isn’t a new concept. Microbes undergo metabolism just like humans do. If you feed a microbe food, it’s going to make a metabolite, and these metabolites just got a new name: Postbiotics.6

What is a Postbiotic?

Postbiotics are defined as the metabolic byproducts (active metabolites) of live microorganisms (bacteria, virus, fungi, and archea), derived from either metabolism of prebiotics or heat-inactivated cell lysis. In fact, postbiotics include more than just the metabolites; they may also include pili, cell wall components or other structures. Importantly, postbiotics do not contain live organisms, just their components or their metabolites.6 And, these molecules may have global physiological effects on the host.

More simply put, postbiotics are the active substances our microbiome makes from the nutrients we eat (i.e. fiber and polyphenols) to communicate with our body and maintain health.

The idea of using a postbiotic, instead of prebiotic or probiotic, is still a novel concept. Administering the end product means that we don’t have to hope that the microorganisms in a person’s microbiome are going to act the way we want or expect them to. Postbiotics may be able to trigger our own commensal bacteria to behave differently and impact our immune system just as probiotics do.7 What is even more important is the fact that postbiotics are considered more safe because they don’t contain anything that is alive.

The sourcing of postbiotics may also be an important component of how they work, similar to prebiotics and probiotics. Postbiotics can be harvested from bacteria in vitro, or from bacterial lysates. In this case, the number of metabolites would be limited to the particular species grown and the food (prebiotics) they are fed. The richest source of postbiotics is likely the gut microbiome of a healthy individual who eats a plant-based diet, with its diverse set of microbes and rich nutrient base.8-10

What does this mean for the Future of Microbiome Therapeutics?

As the field of microbiome related therapeutics (e.g. probiotics, probiotics, postbiotics, parabiotics, and more) continues to grow, we hope that the benefits broaden as well so that we can better aid the treatment of human disease and suffering.

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References

  1. Hill C, Guarner F, Reid G, et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514. doi:10.1038/nrgastro.2014.66
  2. Ferrarese R, Ceresola ER, Preti A, Canducci F. Probiotics, prebiotics and synbiotics for weight loss and metabolic syndrome in the microbiome era. Eur Rev Med Pharmacol Sci. 2018;22(21):7588-7605. doi:10.26355/eurrev_201811_16301
  3. Mörkl S, Butler MI, Holl A, Cryan JF, Dinan TG. Probiotics and the Microbiota-Gut-Brain Axis: Focus on Psychiatry. Curr Nutr Rep. 2020;9(3):171-182. doi:10.1007/s13668-020-00313-5
  4. Pattani R, Palda VA, Hwang SW, Shah PS. Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium difficile infection among hospitalized patients: systematic review and meta-analysis. Open Med Peer-Rev Indep Open-Access J. 2013;7(2):e56-67.
  5. Davani-Davari D, Negahdaripour M, Karimzadeh I, et al. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods. 2019;8(3):92. doi:10.3390/foods8030092
  6. Salminen S, Collado MC, Endo A, et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol. 2021;18(9):649-667. doi:10.1038/s41575-021-00440-6
  7. Żółkiewicz J, Marzec A, Ruszczyński M, Feleszko W. Postbiotics—A Step Beyond Pre- and Probiotics. Nutrients. 2020;12(8):2189. doi:10.3390/nu12082189
  8. Clem J, Barthel B. A Look at Plant-Based Diets. Mo Med. 2021;118(3):233-238.
  9. Cotillard A, Cartier-Meheust A, Litwin NS, et al. A posteriori dietary patterns better explain variations of the gut microbiome than individual markers in the American Gut Project. Am J Clin Nutr. Published online October 7, 2021:nqab332. doi:10.1093/ajcn/nqab332
  10. Dahl WJ, Rivero Mendoza D, Lambert JM. Chapter Eight - Diet, nutrients and the microbiome. In: Sun J, ed. Progress in Molecular Biology and Translational Science. Vol 171. The Microbiome in Health and Disease. Academic Press; 2020:237-263. doi:10.1016/bs.pmbts.2020.04.006
  11. Piqué N, Berlanga M, Miñana-Galbis D. Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci. 2019;20(10):2534. doi:10.3390/ijms20102534
  12. Del Toro-Barbosa M, Hurtado-Romero A, Garcia-Amezquita LE, García-Cayuela T. Psychobiotics: Mechanisms of Action, Evaluation Methods and Effectiveness in Applications with Food Products. Nutrients. 2020;12(12):3896. doi:10.3390/nu12123896
  13. Ojeda J, Ávila A, Vidal PM. Gut Microbiota Interaction with the Central Nervous System throughout Life. J Clin Med. 2021;10(6):1299. doi:10.3390/jcm10061299