Completing the Circle by Adding Postbiotics to Your Prebiotic and Probiotic Regime

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Nutritional science is now recognizing the necessity and health promoting potential of maintaining symbiosis in the human gastrointestinal microbiome.  The therapeutics approach to this ongoing maintenance is the consumption of three categories of natural substances that can strengthening the microbiota.  These three categories include:

  • Prebiotics
  • Probiotics
  • Postbiotics

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Figure 1.  Mechanisms of action of probiotics at the cellular level in intestinal epithelia.  (Source:  Therapeutic Use of Prebiotics, Probiotics, and Postbiotics to Prevent Necrotizing Enterocolitis: What is the Current Evidence?)

Prebiotics is a non-digestible food fiber, wither as a supplement or a food, that promotes the growth of indigneous bacteria in the gut.  Prebiotics survive digestion from the stomach and small intestine and arrive in the large intestine intact, at which point they are digested and fermented by the commensal bacteria.  The purpose of prebiotics is to boost the production of probiotics and provide food for the growth of additional beneficial bacteria.  Foods that contain prebiotics include grains, vegetables, and roots.  Specific prebiotics used as supplements include galacto-oligosaccharides, arabinogalactans, fructo-oligosaccharides, and inulin.

Probiotics are microorganisms that alter and have a beneficial effects on the human microbiome.  Probiotics are found in foods and supplements.

Probiotics combined with prebiotics, usually in supplement form, are often called synbiotics. Examples include Lactobacillus acidophilus and Bifidobacterium bifidum with fructo-oligosaccharides.

Postbiotics are substances produced in the final or intermediate stage of metabolic process in lactic acid bacteria.  They are effectively probiotic metabolic byproducts and non-viable bacterial products.  They stimulate the growth of beneficial bacteria in the gut.  

Postbiotics complete the trinity of natural substances that are the key factors in maintaining long-term digestive health.

The various metabolic byproducts produce as postbiotics include:

  • short chain fatty acids
    • acetate
    • butyrate
    • propionate
  • indole, derived from tryptophan
  • polysaccharide A 
  • exopolysaccharide
  • lactocepin
  • p40 molecule
  • teichoic acid
  • peptidoglycan derived muropeptides
  • cell surface and secreted proteins
  • bacteriocins

Postbiotics possess a myriad of beneficial probiotic effects, including, but not limited to:  1

  • their ability to reduce pH value thereby inhibiting opportunistic pathogens in the feed and gut of animals. In addition, postbiotics
  • display wide inhibitory activity against various species of pathogens such as Listeria monocytogenes, Clostridium perfringens, Salmonella enterica, and Escherichia coli
  • A Bifidobacterium brevestrain expressing cell-surface associated exopolysaccahride (EPS) significantly inhibited colonisation of mouse intestines by the pathogen Citrobacter rodentium  2
  • Another not yet identified soluble mediator released in culture supernatant was responsible for the anti-inflammatory effect of F. p r a us n i tz i i and shown to correct dysbiosis associated with the 2,4,6-trinitrobenzene sulfonic acid (TNBS) model of colitis  3

Of all the postbiotics listed above, it is probably the short-chain fatty acids that are subject to the most research and represent the most important of the postbiotics.  Fortunately, SCFA’s, specifically butyrate and propionate can also be found as a specific supplement for consumption.  

Prebiotic fibers, such as resistant starches, green banana flour and other dietary fibers ferment in the large intestine to produce short-chain fatty acids (SCFA).  The three main SFCA include:  acetate, propionate, and butyrate.

The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time. SCFAs are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. Specific SCFA may reduce the risk of developing gastrointestinal disorders, cancer, and cardiovascular disease. Acetate is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis.

Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification.

Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect.   4  

Short-chain fatty acids are of the most important postbiotics of the microbiome.  They affect a large range of physiological processes that have beneficial consequences on the composition of the gut microbiome and general colon health.

The Table below lists the physiological effects of the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate:

Table 1: Overview of the physiological effects of the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate produced by human colon bacteria

SCFAPhysiological effect
Acetate CH 3 -COO −Reaches the portal vein and is metabolized in various tissues
Intestinal effects
Is a minor energy source for the colon epithelial cells
Decreases the pH of the colon (which decreases bile salt solubility, increases mineral absorption, decreases ammonia absorption, and inhibits growth of pathogens)
Has anti-inflammatory effects
Increases colonic blood flow and oxygen uptake
Is used by cross-feeding species as a co-substrate to produce butyrate
Other effects
Is a substrate for cholesterol and fatty acid biosynthesis in the liver
Is an energy source for muscle and brain tissue
Propionate CH 3 -CH 2 -COO −Reaches the portal vein and is subsequently taken up by the liver
Intestinal effects
Is a minor energy source for the colon epithelial cells
Decreases the pH of the colon (which decreases bile salt solubility, increases mineral absorption, decreases ammonia absorption, and inhibits growth of pathogens)
Prevents proliferation and induces apoptosis of colorectal cancer cells
Interacts with the immune system
Has anti-inflammatory effects
Other effects
Promotes satiety
Lowers blood cholesterol levels
Decreases liver lipogenesis
Improves insulin sensitivity
Butyrate CH 3 -CH 2 -CH 2 -COO −Is mainly taken up by the colon epithelial cells, only small amounts reach the portal vein and the systemic circulation
Intestinal effects
Is the preferred energy source for the colon epithelial cells
Decreases the pH of the colon (which decreases bile salt solubility, increases mineral absorption, decreases ammonia absorption, and inhibits growth of pathogens)
Stimulates proliferation of normal colon epithelial cells
Prevents proliferation and induces apoptosis of colorectal cancer cells
Affects gene expression of colon epithelial cells
Plays a protective role against colon cancer and colitis
Improves the gut barrier function by stimulation of the formation of mucin, antimicrobial peptides, and tight-junction proteins
Interacts with the immune system
Has anti-inflammatory effects
Stimulates the absorption of water and sodium
Reduces oxidative stress in the colon
Other effects
Promotes satiety

Table 1:  Overview of the physiological effects of the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate produced by human colon bacteria (Hamer et al., 2008; Al-Lahham et al., 2010; Havenaar, 2011; Macfarlane and Macfarlane, 2012; Chang et al., 2014; Louis et al., 2014; Tralongo et al., 2014)  (Source:  Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut)

Informational References:

Postbiotica