The human gut microbiome is a bustling ecosystem of trillions of microorganisms. It has become a focal point in modern health science. You likely have heard discussion of probiotics and maybe even prebiotics, but have you heard about postbiotic metabolites? They are the latest and maybe most intriguing components of the gut microbiome currently being discussed. These are not just byproducts of the interaction of probiotics; they are powerful mediators of health, influencing everything from immune function to mental well-being.

Postbiotics are the metabolic end products of probiotic bacteria and other beneficial microbes. Unlike probiotics, which are live organisms, postbiotics are non-living, bioactive compounds. Beneficial bacteria produce postbiotic metabolites as they interact with our digestive system. Postbiotic metabolites act as the microbiome’s “messengers,” communicating with our cells to regulate digestion, immunity, and even brain function.

There are various mechanisms that result in the production of postbiotic metabolites. The most common ways, include fermentation, degradation of complex molecules, or the synthesis of new compounds. Think of them as the far from useless “waste products” of microbial activity.

Postbiotic metabolites bridge the gap between diet, microbiome, and human physiology. Unlike probiotics, they bypass challenges like bacterial survival in the gut, making them a promising tool for targeted therapies. Their benefits extend beyond digestion:

• Strengthen Gut Barrier Integrity: Aid in preventing “leaky gut” and systemic inflammation.

• Mental Health: Some gut-derived metabolites are neurotransmitters that highlight the microbiome’s role in mood disorders. The understanding of postbiotic metabolites have given rise to the term: the gut-brain axis.

• Modulate Immunity: Help in balancing immune responses to avoid overreactions (allergies) or underreactions (infections).

• Combat Pathogens: Creating an inhospitable environment for harmful microbes.

• Personalized Medicine: Tailored postbiotic supplements could address individual gut imbalances that assist in targeting specific health issues.

Postbiotic metabolites come in several forms. They can be enzymes, organic acids, peptides, and other signaling molecules. Some common classes of postbiotics include:

SCFAs include butyrate, propionate, and acetate. They are produced by the fermentation of dietary fibers by beneficial microorganisms. Some benefits of SCFAs include:

• Energy Source: SCFAs fuel colon cells, maintaining gut barrier integrity.

• Anti-Inflammatory: Butyrate suppresses inflammation, reducing risks of conditions like Crohn’s disease.

• Immune Modulation: Propionate supports immune cells and regulates metabolism.

• Mental Health: Linked to reduced anxiety and depression via gut-brain axis signaling.

Bacteriocins are bioactive peptides typically synthesized by lactic acid bacteria. They are made when proteins are broken down by bacterial enzymes. The main benefit of bacteriocins is that they inhibit the growth of harmful microbes and play a key role in maintaining gut balance. Another byproduct of bacteriocins is Beta-Glucuronidase. This compound helps recycle hormones and support liver detox pathways by breaking glucuronic acid bonds making them water soluble and easier to excrete.

Exopolysaccharides are complex carbohydrates (sugars) secreted by bacteria like Bifidobacterium infantis.

EPS have several benefits:

• Gut Barrier Support: EPS bind to intestinal cells, reinforcing the mucosal lining and preventing “leaky gut.”

• Detoxification: EPS have been shown to adsorb heavy metals and pathogens, reducing their harm in the treatment of wastewater. This is theorized to also occur in the microbiome.

• Probiotic Enhancer: Protect beneficial bacteria from stomach acid, improving survival. This is an important consideration when using probiotics to try to increase gut microbiome diversity.

Some microorganisms produce H₂S via the fermentation of undigested carbohydrates. Sulfate-reducing bacteria also produce this from sulfur-containing amino acids.

The benefits of H₂S include:

• Promotes Cardiovascular Health: Dilates blood vessels, which may help in lowering blood pressure.

• Neuroprotection: May slow Alzheimer’s progression by enhancing mitochondrial function.

• Anti-Inflammatory: Reduces colitis severity by suppressing pro-inflammatory cytokines.

Bacteria like Bifidobacterium and E. coli are responsible for synthesizing many of the B vitamins and Vitamin K in the microbiome. B vitamins are necessary to aid energy production, brain function, and red blood cell formation. Vitamin K is essential for blood clotting and bone health.

Lactate is produced by Lactobacillus during anaerobic fermentation of simple carbohydrates.

The main benefits of lactate include:

• pH Regulation: Lowers gut acidity, preventing pathogen overgrowth.

• Energy for Gut Cells: Serves as a substrate for colonocytes.

• Microbiome Balance: Supports growth of beneficial microbes like Bifidobacteria.

Urolithins result from the transformation of ellagitannins by the gut bacteria. Studies have shown urolithins to have wide ranging impacts on muscle fitness, mitochondrial support and longevity. They are a postbiotic metabolite that is highly dependent on having the right gut microbiome diversity.

While not strictly microbial metabolites, gut bacteria heavily influence production of the following neurotransmitters:

GABA is produced by certain beneficial bacteria, such as Lactobacillus brevis and Bifidobacterium dentium. It plays a crucial role in regulating gut motility, stress response, and mood.

Over 90% of the body’s serotonin is made in the gut, influenced by bacteria like Enterococcus and Streptococcus. Regulation of mood, appetite, and gut motility are all influenced by serotonin.

Catecholamines are a class of neurotransmitters including dopamine, norepinephrine and epinephrine. Both the gut and the brain produce catecholamines. They are involved in regulating stress response, mood, and motivation.

Several varieties of beneficial bacteria produce histamine. It plays a role in regulating gut motility, immune response, and allergic reactions. Often, the immunity modulation effects of other postbiotic metabolites is related to the production and regulation of histamine.

Lactobacillus and Bifidobacterium produce glutamate. Glutamate is an excitatory neurotransmitter. It has involvement in regulating gut motility, learning, and memory.

Acetylcholine plays a role in regulating gut motility, muscle contraction, and cognitive function.

Based on what we now know about postbiotic metabolites, some strategies to boost postbiotic metabolite production might be obvious. The ultimate goals are to increase probiotic diversity and create an environment to encourage the best probiotics to thrive. These include:

1. Eat Diverse Fibers: Whole grains, legumes, fruits, and vegetables feed beneficial bacteria.

2. Fermented Foods: Yogurt, kimchi, and kefir introduce probiotic strains that produce postbiotics.

3. Polyphenol-Rich Foods: Berries, dark chocolate, and green tea enhance microbial diversity.

While these are your best strategies for encouraging postbiotic metabolites, there are no emerging products that isolate specific metabolites. Unlike probiotics (live bacteria) or prebiotics (food for bacteria), postbiotics are non-living compounds. This makes them stable, easy to store, and potentially more targeted in their effects.

Because of the difficulty for most people to produce urolithins, this is one of the main metabolites that people have been taking as a supplement. I used to take probiotics, but noticed via testing that that didn't always lead to beneficial impacts to my microbiome. I've since switched to focusing more on diet, making sure I get plenty of prebiotics and have recently added in Dr. Ohhira's original probiotic product. This mainly consists of a ton of postbiotic metabolites created via a fermentation process that mimics what occurs in the gut.

Postbiotic metabolites represent a new frontier in gut health research, offering a deeper understanding of the intricate relationships between the microbiome, gut, and brain. Researchers are now exploring postbiotic therapies for various conditions. Unlike probiotics, which may struggle to colonize the gut, postbiotics offer a direct way to harness the microbiome’s benefits without relying on live bacteria. By harnessing the power of these metabolites, we may be able to develop novel therapeutic strategies, proving that the microbiome’s influence extends far beyond its microbial residents. Have you tried postbiotics? Drop a line in the comments with your experience!