Postbiotic Explained

Postbiotics - also known as metabiotics, biogenics, or simply metabolites - are soluble factors (metabolic products or byproducts), secreted by live bacteria, or released after bacterial lysis providing physiological benefits to the host.^[1]

However, this term is sometimes also used with regards to paraprobiotics - immobilised probiotics, which when ingested, may have the ability to exert positive biological responses and restore intestinal homeostasis in a similar manner to probiotics.^[2] Paraprobiotics are currently being referred to as modified,^[3] inactivated, non-viable,^[4] para- or ghost probiotics.^[5] Probiotics are widely used and accepted in many countries in clinical practice. Paraprobiotics, the immobilised version of probiotics are gaining traction in recent years due to the concerns about the possibility of low tolerance of probiotics, especially in paediatric populations and in severely ill or immunocompromised patients.^[6] Paraprobiotics seem to have similar beneficial properties as live probiotics with fewer of the constraints associated with unstable, diminishing bacteria.

Paraprobiotics types

Paraprobiotics could be generated using different methods:

• Heat-inactivation (also includes tyndallisation)
• Ultraviolet-inactivated
• Chemical treatment (e.g. formalin)
• Gamma-irradiation
• Sonication

In most cases heat treatment is considered the method of choice for deactivating probiotic strains. The effect that different types of inactivation have on bacterial structure and components as well as the maintenance of probiotic properties requires further research.

Mechanism of action

The mechanisms of action for paraprobiotics is less understood, though the possible mechanisms include immune system regulation and interference with pathogen attachment to host cells. Limited research hypothesises that immobilised paraprobiotics release key bacterial components, such as lipoteichoic acids, peptidoglycans, or exopolysaccharides which exhibit key immunomodulating effects and antagonising properties against pathogens.

General paraprobiotics applications

As paraprobiotics are newly emerging, so is the evidence to support the use of paraprobiotics. Emerging clinical and pre-clinical studies have demonstrated that paraprobiotics play a role in general health and well-being and for improving host immune function like that of probiotics.^{[7] [8] [9]} It is postulated that paraprobiotics induce changes in the gut microbiome and the altered gut microbial composition which are associated with increased levels of innate and acquired immunity biomarkers.^[10] Paraprobiotics also seem to exhibit antioxidant effects highlighting their potential applications in food and pharmaceutical industries.^[11]

Paraprobiotics applications in biotherapy

Paraprobiotics (mostly heat-killed) have been evaluated in small study sizes and seem to be beneficial for the following clinical applications:

• Gastrointestinal diseases (bloating, paediatric disorders, infantile colic, diarrhea, extra-intestinal diseases)
• Upper respiratory tract infections
• Ocular disorders including eye fatigue^[12]
• There is a growing body of pre-clinical evidence supporting the use of paraprobiotics for the following applications:
• Asthma^[13]
• Inflammatory bowel diseases (ulcerative colitis)^{[14] [15]}
• Colitis-associated colorectal cancer^[16]
• Type 2 Diabetes (improved glycemic parameters)^[17]
• Liver injury^{[18] [19]}
• Atopic dermatitis^[20]
• Influenza viruses^{[21] [22] [23]}
• Cardiac injury^[24]

Species used as paraprobiotics

Many species of bacteria have been identified to have benefits as paraprobiotic strains:

• Bifidobacterium breve ^{[14] [15]}
• Bifidobacterium infantis ^{[14] [15]}
• Bifidobacterium longum ^{[14] [15]}
• Enterococcus faecalis ^{[16] [20]}
• Lactobacillus acidophilus ^{[14] [15]}
• Lactobacillus brevis^{[20] [25]}
• Lactobacillus bulgaricus ^{[14] [15]}
• Lactobacillus casei^{[14] [15] [26]}
• Lactobacillus delbrueckii subsp. Bulgaricus^[27]
• Lactobacillus fermentum ^[27]
• Lactobacillus johnsonii ^[18]
• Lactobacillus paracasei ^{[7] [8]}
• Lactobacillus plantarum ^{[10] [11] [13] [14] [15] [21]}
• Lactobacillus reuteri^{[24] [28]}
• Lactobacillus salivarius ^[18]
• Lactococcus lactis^[9]
• Streptococcus salivarius subsp. thermophilus^{[14] [15] [17]}

References

1. Aguilar-Toalá JE, Garcia-Varela R, Garcia HS, Mata-Haro V, González-Córdova AF, Vallejo-Cordoba B, Hernández-Mendoza A . Postbiotics: An evolving term within the functional foods field . Trends Food Sci Technol . 2018 . 75 . 105–114 . 10.1016/j.tifs.2018.03.009 .
2. Popovic, N., et al, The Influence of Heat-Killed Enterococcus faecium BGPAS1-3 on the Tight Junction Protein Expression and Immune Function in Differentiated Caco-2 Cells Infected With Listeria monocytogenes ATCC 19111. Front Microbiol 2019, 10 pages412
3. Zorzela, L., et al., Is there a role for modified probiotics as beneficial microbes: a systematic review of the literature. Benef Microbes, 2017. 8(5): p. 739-754.
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8. Arai, S., et al., Orally administered heat-killed Lactobacillus paracasei MCC1849 enhances antigen-specific IgA secretion and induces follicular helper T cells in mice. PLoS One, 2018. 13(6): p. e0199018.
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16. Chung, I.C., et al., Pretreatment with a Heat-Killed Probiotic Modulates the NLRP3 Inflammasome and Attenuates Colitis-Associated Colorectal Cancer in Mice. Nutrients, 2019. 11(3).
17. Gao, X., et al., Effect of heat-killed Streptococcus thermophilus on type 2 diabetes rats. PeerJ, 2019. 7: p. e7117.
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22. Jung, Y.J., et al., Heat-killed Lactobacillus casei confers broad protection against influenza A virus primary infection and develops heterosubtypic immunity against future secondary infection. Sci Rep, 2017. 7(1): p. 17360.
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24. Liao, P.H., et al., Heat-killed Lactobacillus Reuteri GMNL-263 Prevents Epididymal Fat Accumulation and Cardiac Injury in High-Calorie Diet-Fed Rats. Int J Med Sci, 2016. 13(8): p. 569-77.
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