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Page 8 of 20 Manrique et al. Microbiome Res Rep 2024;3:23 https://dx.doi.org/10.20517/mrr.2023.80

Synbiotics
The combination of probiotics and prebiotics is known as synbiotic products. Initially, synergistic synbiotics
combined probiotics and prebiotics that enhance the functionality of such probiotics. However, most
current symbiotic products are complementary synbiotics, which are defined by the ISAPP as “a mixture of
live microorganisms and substrate(s) selectively utilized by host microorganisms that independently confer
[97]
a health benefit on the host” . Gomez Quintero et al. provide a review of recent examples of
complementary and synergistic synbiotics, along with the rationale behind their formulation .
[98]
Postbiotics
A postbiotic, according to the definition proposed by Salminen et al., refers to a “preparation of inanimate
[93]
microorganisms and/or their components that confers a health benefit to the host” . Postbiotics exert their
benefits indirectly through modulation of the microbiome composition or directly by regulating the
immune system .
[99]
Most of the currently existing postbiotics are derived from bacteria of the Lactobacillus or Bifidobacterium
bacterial genera, but also from yeasts such as Saccharomyces cerevisiae, mainly from the fermentation of
these bacteria carried out in industrial processes [100-105] . Postbiotics are commonly metabolites or
polysaccharides, substances with antioxidants, anti-inflammatory or even immunomodulatory
properties [15,95,100] . One of these interesting metabolites is SCFAs, a product of bacterial fermentation of
dietary fiber in the colon . Thus, an important challenge in the development of postbiotics is the
[15]
identification and isolation of the bioactive metabolites or proteins produced by these bacteria, usually done
by chromatographic or metabolomic techniques .
[100]

Novel postbiotics that could be approved as novel foods in regulatory terms if administered orally include
whole bacterial cells that have been inactivated. For example, in 2019, pasteurized Akkermansia muciniphila
was not approved as QPS but was for use as a novel food ingredient in the European Union. This species
has been associated with a reduction in obesity and with an improvement in diabetes and various
cardiovascular diseases [106,107] . In addition, oral administration of pasteurized A. muciniphila can improve
[108]
obesity rates, reducing body weight . A different study also showed that A. muciniphila can influence
insulin resistance, improving glycemia values and glucose resistance [109,110] .

One of the main advantages of using postbiotics over probiotics is the reduced risk of bacterial translocation
from the intestine to the systemic circulation and bacterial infection. Overall, they are considered safer,
especially in neonates and vulnerable patients [95,99,100] . In addition, postbiotics have a longer shelf life and can
be used more efficiently in topical formulations, as they do not have to be kept viable compared to
probiotics. This is an advantage for their use in the cosmetic industry .
[100]

In spite of certain health benefits reported for many probiotics, the benefit of these products is not always as
robust as desired, most likely due to the high complexity of the gut microbiota ecosystem, and has been a
controversial topic [111-113] . Among other issues, many probiotic strains fail to colonize the intestinal tract
stably after ceasing the treatment and differences in efficacy depending on the strains of the bacteria used
have been reported . To overcome these limitations, great efforts have been invested in the development
[114]
of more robust and efficacious therapies with proven effects and recognition as medical products, including
live biotherapeutic products (LBPs) and FMT.