Postbiotics: The Future of Microbiome Health?

Postbiotics: The Future of Microbiome Health?

What are Gut-Microbiota Derived Metabolites?

Simply put, metabolites are the products made when the body breaks down food, chemicals, or its own tissues. Bacterial-derived metabolites are the postbiotic molecules that result from the fermentation of dietary fibers and resistant starches; eating plenty of these foods will ensure the production of the metabolites necessary for good health. Onions, garlic, leeks, asparagus, and sunchokes are examples of foods that contribute to the production of beneficial lipids (known as short-chain fatty acids) and encourage the growth of keystone commensal bacteria such as lactobacillus.1

”Metabolites are the postbiotic molecules that result from the fermentation of dietary fibers”

What do Metabolites (aka Postbiotics) Do?

Metabolites act as "the hormones of our digestive system", communicating with other bacteria in our gut and crossing the intestinal barrier to drive various biological activities in organs throughout our body.2 Metabolites can provide nourishment to support the environment by feeding the microbiome with appropriate precursors and allowing the "good guys" to flourish while producing bacteriocins to manage the overgrowth of invasive or opportunistic species. This balancing act serves to maintain microbiome homeostasis.

The functions of metabolites impact human health in a variety of ways. The gut microbiota is host to specific metabolic processes that control the bioavailability of micronutrients and vitamins3, help regulate blood sugar4, modulate our immune system5, and produce or influence neurotransmitters that regulate our mood, emotions, and cognitive abilities.6 Considering its ability to influence the function of multiple organs and systems, our gut microbiota can be thought of as a "virtual endocrine organ".

”Metabolites act as the hormones of our digestive system”

The Role of Short-chain Fatty Acids

SCFAs are the major products of the bacterial fermentation of carbohydrates and proteins in the gut.7 The main SCFAs are acetic, propionic, and n-butyric acids. SCFAs maintain the integrity of the intestinal barrier by producing mucus and providing protective anti-inflammatory properties.8 SCFAs also provide energy for cellular growth in distal systems such as your muscles, kidneys, heart, and brain.9 All three metabolites cross the blood-brain barrier (BBB) and are found in human cerebrospinal fluid where they act to regulate the BBB function and maintain its integrity by inducing the expression of tight junction proteins.10-12

SCFAs support our adaptive immune system by inducing the differentiation of T regulatory cells to control and shut down inflammation13,14 and support the maturation of our innate immune system by regulating hematopoiesis.15

Metabolites come in all Shapes and Sizes

Other metabolites produced in the gut include neurotransmitters such as serotonin, dopamine, GABA, and noradrenaline which act to mediate our emotions, cognition, stress, and sleep patterns.16,17 There is a reason we crave comfort foods in times of illness and distress; these familiar foods (e.g. chicken soup and dairy products) are providing our microbes with the nutrients needed (glutamine and tryptophan) that serve as precursors to important neuroactive compounds like serotonin.18

”The existence of beneficial metabolites is more important for healthy metabolic processes… than the composition of the probiotic species”

Research is now showing that the existence of beneficial metabolites is more important for healthy metabolic processes in the body than the composition of the probiotic species population.19 In other words, what your microbes are doing is more important for your health than which bacteria are present, and what they are doing is creating metabolites. The ability to sustain beneficial metabolic activity depends on ensuring your gut microbes are fed correctly with plenty of plant-based foods.

Learn more

References

  1. Sunu P, Sunarti D, Mahfudz LD, Yunianto VD. Prebiotic activity of garlic (Allium sativum) extract on Lactobacillus acidophilus. Vet World. 2019;12(12):2046-2051. doi:10.14202/vetworld.2019.2046-2051
  2. Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG. Minireview: Gut microbiota: the neglected endocrine organ. Mol Endocrinol. 2014;28(8):1221-1238. doi:10.1210/me.2014-1108
  3. Yoshii K, Hosomi K, Sawane K, Kunisawa J. Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity. Front Nutr. 2019;6:48. doi:10.3389/fnut.2019.00048
  4. Utzschneider KM, Kratz M, Damman CJ, Hullar M. Mechanisms Linking the Gut Microbiome and Glucose Metabolism [published correction appears in J Clin Endocrinol Metab. 2016 Jun;101(6):2622]. J Clin Endocrinol Metab. 2016;101(4):1445-1454. doi:10.1210/jc.2015-4251
  5. Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes. 2012;3(1):4-14. doi:10.4161/gmic.19320
  6. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13(10):701-712. doi:10.1038/nrn3346
  7. Kovatcheva-Datchary P, Arora T. Nutrition, the gut microbiome and the metabolic syndrome. Best Pract Res Clin Gastroenterol. 2013;27(1):59-72. doi:10.1016/j.bpg.2013.03.017
  8. O’Keefe SJD. Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol. 2016;13(12):691-706. doi:10.1038/nrgastro.2016.165
  9. Cummings JH, Englyst HN. Gastrointestinal effects of food carbohydrate. Am J Clin Nutr. 1995;61(4):938S - 945S. doi:10.1093/ajcn/61.4.938S
  10. Wishart DS, Tzur D, Knox C, et al. HMDB: the Human Metabolome Database. Nucleic Acids Res. 2007;35(Database issue):D521-D526. doi:10.1093/nar/gkl923
  11. Sun J, Ling Z, Wang F, et al. Clostridium butyricum pretreatment attenuates cerebral ischemia/reperfusion injury in mice via anti-oxidation and anti-apoptosis. Neurosci Lett. 2016;613:30-35. doi:10.1016/j.neulet.2015.12.047
  12. Braniste V, Al-Asmakh M, Kowal C, et al. The gut microbiota influences blood-brain barrier permeability in mice [published correction appears in Sci Transl Med. 2014 Dec 10;6(266):266er7. Guan, Ng Lai [corrected to Ng, Lai Guan]]. Sci Transl Med. 2014;6(263):263ra158. doi:10.1126/scitranslmed.3009759
  13. Arpaia N, Campbell C, Fan X, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451-455. doi:10.1038/nature12726
  14. Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569-573. doi:10.1126/science.1241165
  15. Thiruvengadam M, Subramanian U, Venkidasamy B, et al. Emerging role of nutritional short-chain fatty acids (SCFAs) against cancer via modulation of hematopoiesis [published online ahead of print, 2021 Jul 28]. Crit Rev Food Sci Nutr. 2021;1-18. doi:10.1080/10408398.2021.1954874
  16. Perna S, Alalwan TA, Alaali Z, et al. The Role of Glutamine in the Complex Interaction between Gut Microbiota and Health: A Narrative Review. Int J Mol Sci. 2019;20(20). doi:10.3390/ijms20205232
  17. Hyland NP, Cryan JF. A Gut Feeling about GABA: Focus on GABA(B) Receptors. Front Pharmacol. 2010;1:124. Published 2010 Oct 4. doi:10.3389/fphar.2010.00124
  18. Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int J Tryptophan Res. 2009;2:45-60. doi:10.4137/ijtr.s2129
  19. Visconti A, Le Roy CI, Rosa F, et al. Interplay between the human gut microbiome and host metabolism. Nat Commun. 2019;10(1):4505. doi:10.1038/s41467-019-12476-z