Postbiotics; the real end-game of probiotics and prebiotics.

citations: (Cabello-Olmo et al., 2021; Martyniak et al., 2021; Mishra et al., 2024; Panghal et al., n.d.; Petrof et al., 2013; Yoshimatsu et al., 2021)

Conditions of Autoimmunity (like Rheumatoid Arthritis and Inflammatory bowel Disease), Skin Conditions (Like Psoriasis, Eczema, and Acne), and chronic inflammatory conditions all have one thing in common.  These conditions leave us looking toward the digestive system and the Microbiome  as to what is driving these disorders. Rightfully so, the gut is a main source of energy production, immune response, and inflammation control. 

But what are we looking for in the gut? 

The answer is evolving. However, some people look at the health of the probiotic/commensal microbes. The presence or absence of gut pathogens. The lack or completeness of enzymes and gut digestive function. Or even the presence or lack of inflammation makers or intestinal permeability markers.  This information steers us on how to balance the gut with digestive aids, prebiotics, probiotics, inflammation modulators, etc.

All of these areas are important, and it turns out a growing amount of emphasis is being placed on the presence, balance, and types of microbe-produced postbiotics.

Postbiotics are structural and metabolic microbial products that are released by live or dead microorganisms. This is different then prebiotics and probiotics.  Prebiotics like inulin, Frucotoligosaccharides, Galactooligosaccharides, polyphenols, Xyololigosaccharides, Pectin, Fucoidan, Arabinoxylan, proanthocyanins, and resistant starch; feed microbes to lead to their growth, expansion, and survival. Probiotics are actual habitants of the normal healthy microbiome like Bifidobacterium species, Lactobacillus species, Akkermansia muciniphilia, Faecalibacterium prausnitzii, and members of the Clostrida family of commensal organisms. Probiotics have a wide range of health benefits; one of those being the production of postbiotics.  Now postbiotics are being researched, produces, and offered as treatment for various health conditions as they are considered:

• Anti-inflammatory

• Antioxidant

• Immunomodulatory

• Pathogen inhibitory

• Anti-obesogenic

• Anticancer

• Antitumor

• Antiproliferative

• Antibiofilm

• Anti-adhesion

• Antihypertensive

• Hypocholesterolemic

• Hepatoprotective

• Cardioprotective

• Anti-atherosclerotic

• Anti-ulcerative

When most people think of postbiotics they only think of Short Chain Fatty acids like Butyrate, Acetate, and Propionate. But Postbiotics are much more.  They include cell-free supernatants, bacterial lysates, Cell wall components (e.g., teichoic acids, peptidoglycans, lipoteichoic acids), Peptidoglycan-derived muropeptides, Surface fractions (e.g., S-layer proteins, mucus-binding proteins, fibronectin-binding proteins), various peptides, amino acids, neurotransmitters, enzymes, organic acids, vitamins, minerals, bacteriocins, antimicrobial peptides and fermentation by-products

These are all quite important and I am not covering in detail what each one does. But let me give you an example. Muropeptides are peptidoglycan-derived are metabolites fragments sensed through the innate intracellular receptors NOD1 and NOD2. These metabolites when bound to these receptors actually dampen the onset of conditions like Crohn’s Disease and Ulcerative Colitis. People with a predisposition of these conditions have more of a problem binding Muropeptides derived from peptidoglycans.

Postbiotics are produced by healthy probiotics like Lactobacillus species and Bifidobacterium species, as well as Fungal organisms. Yes, the fungome is quite important not all yeast species in the gut are bad.

Amazingly the probiotic; Akkermansia muciniphilia is thought to produce Glucagon-like-peptide 1 . This the peptide behind semaglutide the weight loss and medication peptide that is highly sought after these days.

Measuring postbiotic health is usually done through a combination of metabolomics and specific postbiotic measurements such as short chain fatty acids.

Postbiotic components in the body can be commercially measured using various techniques including:

• Enzymatic assays: These assays can measure the activity of specific enzymes produced by microorganisms.

• Chromatographic methods: These methods, such as HPLC or LC-MS, can separate and quantify different postbiotic components based on their chemical properties.

• Immunological assays: These assays use antibodies to detect and quantify specific postbiotic components.

• Microscopy:  Microscopy techniques, such as fluorescence microscopy, can visualize and quantify postbiotic components in microbial cultures or food products.

• Culture-based methods: *These methods involve growing microorganisms in controlled conditions to measure the production of postbiotic components.

It is not possible to measure postbiotic components by stool whole genome sequencing because postbiotics are metabolites, not DNA/RNA sequences.

I see some tests like Gut Zoomer by Vibrant labs slowly adding post-biotic components into their analysis. However, we seem to not have many options commercially to really have trustworthy analysis of postbiotics components.

So we are now at a point where we most of the research has been done in animals and monitoring the response of health when manipulating postbiotics.

In addition, we now seeing the appearance of postbiotic supplementation available. Anything from butyrate, Epicor (which increases the post biotic secretory IgA), to Akkermansia Muciniphila probiotics.  We have also the availability of fullspectrum postbiotic from human donors like the one offered through Thaena® . I even came across an interesting Sauerkraut extract postbiotic by Gaia .

In the future, I see postbiotics as being the true biologic medicine in modifying diseases of chronic inflammation. It seems like the fecal transplant will ultimately be replaced by the postbiotic transplant. In the meantime, we must continue to build a balanced microbiome to provide the substrate for making postbiotics.   This includes consuming foods like yogurt, kefir, sauerkraut, and kimchi. But also make yourself deeply intimate with prebiotic rich foods in your diet. See this great handout here.  Have something to add or share? Join the chat below.

References:

Cabello-Olmo, M., Araña, M., Urtasun, R., Encio, I. J., & Barajas, M. (2021). Role of postbiotics in diabetes mellitus: Current knowledge and future perspectives. In Foods (Vol. 10, Issue 7). MDPI AG. https://doi.org/10.3390/foods10071590

Martyniak, A., Medyńska-Przęczek, A., Wędrychowicz, A., Skoczeń, S., & Tomasik, P. J. (2021). Prebiotics, Probiotics, Synbiotics, Paraprobiotics and Postbiotic Compounds in IBD. Biomolecules, 11(12), 1903. https://doi.org/10.3390/biom11121903

Mishra, B., Mishra, A. K., Mohanta, Y. K., Yadavalli, R., Agrawal, D. C., Reddy, H. P., Gorrepati, R., Reddy, C. N., Mandal, S. K., Shamim, M. Z., & Panda, J. (2024). Postbiotics: the new horizons of microbial functional bioactive compounds in food preservation and security. In Food Production, Processing and Nutrition (Vol. 6, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s43014-023-00200-w

Panghal, A., Charan Singh Haryana, C., Kumar Patra, J., Gomes Cruz, A., Gomes da Cruz, A., & Suri, M. (n.d.). Postbiotics: From emerging concept to application.

Petrof, E. O., Gloor, G. B., Vanner, S. J., Weese, S. J., Carter, D., Daigneault, M. C., Brown, E. M., Schroeter, K., & Allen-Vercoe, E. (2013). Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome, 1(1), 3. https://doi.org/10.1186/2049-2618-1-3

Yoshimatsu, Y., Mikami, Y., & Kanai, T. (2021). Bacteriotherapy for inflammatory bowel disease. Inflammation and Regeneration, 41(1), 3. https://doi.org/10.1186/s41232-020-00153-4