Microbiome modulators: postbiotics a new category

‘Biotics’ act in and on the microbiota

A healthy, diverse and rich microbiota in the gastro - intestinal tract plays an essential role in nutrition, immune system function and in disease resistance.1 Every individual has their own distinct microbiota.2 Disturbances of the microbiota composition (dysbiosis) may have many causes, for example: taking antibiotics, dietary imbalance, stress, and disease. This ‘unbalancing’ of the microbiota can lead to overall poor health.3 ‘Biotic’ therapy is intended to correct this dysbiosis and promote good health through the restoration of balance to the microbiota by re ‑ establishing a flourishing and diverse microbial flora.4

Differences between ‘biotics’

The terms ‘biogenics’ or ‘biotics’ include a range of products connected to micro - organisms; the most frequently encountered terms are listed below:

Prebiotics

Substrates that are selectively utilized by host micro ‑ organisms conferring a health benefit.5

Probiotics

Live micro – organisms which when administered in adequate amounts confer a health benefit on the host.6

Synbiotics

Mixtures of probiotics and prebiotics that
beneficially affect the host.7

Postbiotics

A postbiotic is a preparation of inanimate microorganisms and/or their components that confers a health on the host.8

There is particular interest in postbiotics as these agents can provide beneficial effects on health without the potential risks associated with the administration of live micro - organisms.7

Essential criteria to be considered when selecting microbiome modulators

Not all ‘biotics’ are equal when it comes to their beneficial effects and there are many essential criteria to consider:

Strain - dependent properties

Manufacturing processes and storage methods

Proof of efficacy and effective dose

Practical advantages

Safety

Postbiotics : a new category with several advantages

Composition

Postbiotics contain inactivated bacterial strains and/or active metabolites in the fermentation culture.7 Both confer specific properties and efficacy.

Efficacy

The efficacy of postbiotics is not dependent on viability. Inactivation of the micro – organisms in postbiotics ensures that the active substances are delivered to the intestine without any loss of efficacy, and they can be co – administered with antibiotics or antifungals, as well as with hot or cold beverages.9,10 Clinical studies with postbiotics have yielded clear evidence that they are effective in the prevention and treatmet of various types of gastrointestinal diseases, including diarrhea.11 For example, in a meta – analysis comparing 40 studies of inactivated micro – organisms with live probiotics, inactivated micro – organisms were found to be as effective as live probiotics in 86% of trials looking prevention, and in 69% of treatments trials. Furthermore, inactivated micro – organisms were significantly more effective than live micro – organisms in 15% of the treatment trials.12

Mechanism of action

As the inactivation process used with postbiotics cleaves the bacterial cell walls, liberated proteins, metabolites and cellular fragments are able to cross the inner and the outer mucosal layers, providing barrier protection from pathogen adhesion by inhibiting the attachment of pathogens and their internalisation.11 The metabolites can also access the epithelial cells, modulating immune responses.9 Moreover, because these molecules only gradually pass through the mucus layers, they tend to accumulate on the apical side, helping to maintain the barrier’s integrity.9

High stability and easy storage

As postbiotics are inactivated their effectiveness is not dependent upon micro – organism viability and they have a consistent efficacy. Due to the inactivation process, the postbiotics components are stabilized, this guarantee the number of bacterial cells over the time. Inactivation also enables storage and transportation at room temperature without requiring refrigeration to maintain efficacy.9 This may be of particular importance in countries where diarrhea in children is endemic and such infrastructure is less readily available.10

Safety

Postbiotics have a good safety profile, are well tolerated and can generally also be taken by most patient populations, including newborns and infants.9,10 Postbiotics do not transfer antibiotic resistance to the host.

Postbiotics, thanks to the inactivation of the micro - organisms have specific properties, including gradual but steady access to the epithelial cells, a good safety profile with minimal risk of infection, and a high stability, which enables efficacy to be preserved irrespective of coadministration with antibiotics or antifungals. There is also no need for refrigerated storage.9,10

  1. Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ 2018;361:k2179.
  2. Gilbert JA. Our unique microbial identity. Genome Biol 2015;16:97.
  3. Weiss GA, Hennet T. Mechanisms and consequences of intestinal dysbiosis. Cell Mol Life Sci 2017;74:2959-77.
  4. de Almada CN, Almada CN, Martinez RCR, Sant’Ana AS. Paraprobiotics: Evidences on their ability to modify biological responses, inactivation methods and perspectives on their application in foods. Trends Food Science Tech 2016;58:96-114.
  5. Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol 2017;14:491-502.
  6. Hill C, Guarner F, Reid G, et al. Expert consensus document. 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;11:506-14.
  7. Martín R, Langella P. Emerging health concepts in the probiotics field: streamlining the definitions. Front Microbiol 2019;10:1047.
  8. Salminen S, 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. doi:10.1038/s41575-021-00440-6.
  9. Piqué N, Berlanga M, Miñana-Galbis D. Health benefits of heat-killed (tyndallized) probiotics: an overview. Int J Mol Sci 2019;20.
  10. Warda AK, Rea K, Fitzgerald P, et al. Heat-killed Lactobacilli alter both microbiota composition and behaviour. Behav Brain Res 2019;362:213-23.
  11. Liévin-Le Moal V. A gastrointestinal anti-infectious biotherapeutic agent: the heat-treated Lactobacillus LB. Therap Adv Gastroenterol 2016;9:57-75.
  12. Zorzela L, Ardestani SK, McFarland LV, Vohra S. Is there a role for modified probiotics as beneficial microbes: a systematic review of the literature. Benef Microbes 2017;8:739-54.

Diarrhea, a multifactorial disease

Acute diarrhea is defined as the abrupt onset of three or more loose stools per day with increased water content, volume, or frequency and which lasts no longer than 14 days…

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