In recent years, scientific attention has shifted to a relatively nascent area of research that looks promising for future therapeutic applications, postbiotics.
In this article, we will delve into the scope of these supplements, elucidating their importance compared to their more well-known counterparts, pre and probiotics.

By examining a number of scientific studies, this article will aim to provide a comprehensive view of the potential mechanisms, health benefits, and future prospects in microbiome modulation.

Introduction

The human microbiome is a complex ecosystem of bacteria, viruses, fungi, and other microorganisms that plays a critical role in maintaining homeostasis within the body.
This intricate symbiotic relationship between the microbiome and human health has led to an increase in interest in microbiome-targeting interventions, such as probiotics, prebiotics, and the focal point of this article, postbiotics.

Here is the article where we talk specifically about the microbiome topic.

The human body is known to provide shelter for approximately 10¹⁴ species of microorganisms that act through molecular and cellular mechanisms that:

• Contrast the adhesion of pathogenic bacteria
• Improve innate immunity, decrease pathogen-induced inflammation
• They promote intestinal epithelial cell survival, barrier function, and protective responses.

Some of these beneficial effects are determined by factors derived from secreted probiotics, which have recently been identified as “postbiotic” mediators. https://doi.org/10.1042/BCJ20160510

The origin

The gut microbiome is widely studied as a factor influencing the development and course of many diseases, including inflammatory bowel diseases. The increasing incidence and increasing severity of the course of the latter created the need to develop new therapeutic methods.

Postbiotics are bioactive compounds that probiotics produce when they consume prebiotics

To better understand the function of postbiotics, we will start by saying that bacteria in the colon express active enzymes in carbohydrates that grant them the ability to ferment complex carbohydrates, generating metabolites such as short-chain fatty acids (SCFAs).
Three predominant SCFAs, propionate, butyrate, and acetate, are typically found in a 1:1:3 ratio in the gastrointestinal tract.
These SCFAs are rapidly absorbed by intestinal epithelial cells where they are involved in the regulation of cellular processes such as gene expression, chemotaxis, differentiation, proliferation, and apoptosis.
The evolution of postbiotics attracted the attention of many researchers due to the emergence of clear structural chemical properties, safety dose limitations, long shelf life, as well as the resulting products of various signaling molecules that regulate various functions, such as: https://doi.org/10.1038/nature12721

• Antiinflammatory
• Immunomodulatory
• Anti-obesogenic activities
• Antihypertensives
• Hypocholesterolemic
• Antiproliferative
• Antioxidants

Acetate is produced by most intestinal anaerobes, while propionate and butyrate are produced by different subsets of gut bacteria that follow distinct molecular pathways.
Butyrate is produced from carbohydrates through glycolysis and acetoacetyl-CoA, while two pathways, the succinate or propanediol, pathway are known for propionate formation, depending on the nature of the sugar.
In the human gut, propionate is mainly produced by Bacteroidetes, while butyrate production is dominated by Firmicutes.

Following a review of the role of SCFAs in human metabolism, butyrate was found to be known for its anti-inflammatory and anti-cancer activities.
Butyrate is an especially important energy source for colonocytes and a decreasing gradient from lumen to crypt is suggested to control intestinal epithelial renewal and homeostasis.
It also increases apoptosis and exfoliation of the cells closest to the lumen.
Butyrate may attenuate bacterial translocation and improve intestinal barrier function by affecting the assembly of tight junctions and mucin synthesis.

Butyrate as an anti-inflammatory and anti-cancer can attenuate bacterial translocation and improve intestinal barrier function

SCFAs also appear to regulate hepatic lipid and glucose homeostasis through complementary mechanisms.
In the liver, propionate can activate gluconeogenesis, while acetate and butyrate are lipogenic.
Both play a role in the regulation of the immune system and the inflammatory response by influencing the production of cytokines, for example, by stimulating the production of IL-18, an interleukin involved in the maintenance and repair of epithelial integrity.

Butyrate and propionate are inhibitors of histone deacetylase that epigenetically regulates gene expression.
SCFAs have also been shown to modulate the regulation of appetite and energy intake through receptor-mediated mechanisms.

Propionate has beneficial effects in humans by acting on β cell function and attenuating reward-based eating behavior through striatal pathways.
Microbial metabolites other than SCFAs have been reported to have an impact on gut barrier functions, epithelial proliferation, and the immune system. https://doi.org/10.1042/BCJ20160510

Why postbiotics over probiotics?

In recent years, postbiotics have emerged as a novel concept within the microbiome realm.
Unlike probiotics, postbiotics do not involve live microorganisms.
Instead, they are the bioactive compounds and metabolic byproducts resulting from the fermentation process of probiotics within the gut.

Probiotics are viable bacteria that present problems with dose standardization and unpredictability.
However, these problems are not associated with postbiotics.
In addition to the longer shelf life, postbiotics are easy to store and transport, and easy to maintain (probiotics need a lower temperature for storage).

The production technology and quantitative control in the case of postbiotics (excluding bacterial lysates) are much faster and more accurate compared to probiotics (excluding bacterial lysates)

An example of postbiotics are metabolites such as short-chain fatty acids (SCFAs)

In the context of safety, postbiotics are safer than probiotics.
In addition, postbiotics avoid the problems of receiving virulence factors and antibiotic resistance genes that could occur in the case of probiotics.

Postbiotics are considered a feasible option for therapeutic interventions for a number of allergic disorders due to their ability to enhance immune system maturation through restoring the balance between Th1/Th2-mediated immunity. https://doi.org/10.1016/j.fufo.2021.100043

Clinical applications and efficacy

While the potential of postbiotics is promising, challenges abound.
Variability in postbiotic composition, limited standardization, and elucidation of optimal doses pose obstacles.
However, ongoing research efforts, fueled by initiatives such as the Human Microbiome Project, offer a glimpse into the future landscape of postbiotic therapies.
The convergence of multidisciplinary collaborations, leveraging genomics, metabolomics, and computational modeling, promises to refine postbiotic interventions.

Scientists believe that postbiotics may be the smarter alternative to the practice of giving whole bacteria for people suffering from various allergic and inflammatory conditions.
Postbiotics have the ability to reduce inflammation and may help maintain gut and colon homeostasis, and could become the next wave of supplements to promote better gut health https://doi.org/10.3390/ijms20194673

Conclusion

The imbalance in the gut microbiota has serious consequences on the development of human diseases such as intestinal inflammation, cardiovascular disorders, type II diabetes, obesity, cancer, respiratory disorders, and the behavioral diseases of Alzheimer’s and Parkinson’s.

The exploration of postbiotics represents an exciting paradigm shift in microbiome modulation.
While probiotics and prebiotics continue to play an important role, the emergence of postbiotics would offer an innovative avenue for targeted and sustainable interventions.

As the scientific community deepens its investigations, encompassing the complexities of postbiotic interactions, we stand on the threshold of a new era in precision medicine, where the intricate symphony of the microbiome can be harmonized through the domain of postbiotic science.

Although the microbial modulations of postbiotics do not consist of live microorganisms, but rather perform similar beneficial health effects through mechanisms that are known to be a prominent feature of probiotics, along with them they also minimize the cause of the risks associated with their consumption.