The -biotics family includes metabolites, nutrients, microbes, and food components that affect gut health – and their newest member is postbiotics, or otherwise known as paraprobiotics.
While there is still much confusion with consumers and some health providers about the term, we’re here to help you understand paraprobiotics and how they relate to probiotics and prebiotics. We will tell you where to find paraprobiotics, how they’re made, what they do, and the benefits they have. Also, we’re going to look at some of the future uses that are being studied.
As is commonplace in research and scientific circles, we will be using the term postbiotics and the term paraprobiotics interchangeably. Right now, researchers are using them both to mean the same microbes.
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What are Paraprobiotics?
Researchers and scientists have known about the postbiotic process for years, even if there isn’t a formal definition set yet for what it is. While fermented foods or the fermentation process of probiotics in the gut result in postbiotic benefits, they also incorporate inactivated microbial strains.
Postbiotics are at times known as paraprobiotics, which are “non-viable microbial cells (intact or broken) or crude cell extracts (i.e., with complex chemical composition), which, when administered (orally or topically) in adequate amounts, confer a benefit on the human or animal consumer,” according to Nutrients.
When prebiotics feed probiotics in your gut, there is fermentation. This fermentation process produces paraprobiotics as a byproduct or as ‘waste.’
These waste product paraprobiotics include carbon substrates, enzymes, and organic acids that help regulate the microbiome composition. While it is considered a waste product, it provides very beneficial results in the body.
The differences between gut bacteria types will create varying kinds of paraprobiotics. Over 800 different types are known right now, and they include enzymes for metabolism, amino acids, and short-chain fatty acids for optimal gut health. The more diverse that the probiotic bacteria are, the better the gut health will be.
Paraprobiotics are naturally created in the body, but they can be added through external means too. Additionally, there is a very tight bond between prebiotics, probiotics, and paraprobiotics and how they interact to create a balanced gut flora to keep your body healthy.
Some of the other key positives to postbiotics include:
- More stable than probiotics
- Longer shelf life than probiotics due to ‘dead’ bacteria versus ‘live’ bacteria
- No strict storage or production conditions, so it can be manufactured and stored in more areas than with probiotics.
- Better for the immunocompromised, which are not supposed to take probiotics but still need their benefit
Production of Paraprobiotics
Paraprobiotics are usually produced by cell disruption techniques like heat, solvent extraction, sonication, and enzymatic treatments.
However, the post-production process has extra steps, including centrifugation, extraction, dialysis, freeze-dried purification, and column purification. According to the International Journal of Current Microbiology and Applied Science, all of these methods combine to produce and identify paraprobiotics.
Classes of Paraprobiotics
Research published in Nutrients notes that classes of paraprobiotics include exopolysaccharides, enzymes, cell-free supernatants, cell wall fragments, bacterial lysates, metabolites produced by gut microbiota, and short-chain fatty acids.
Biopolymers are produced by microorganism growth with varying chemical properties. When these biopolymers are released outside of the bacterial cell wall, they may form a group of heterogeneous substances called exopolysaccharides or EPSs.
Exopolysaccharides are used as water-binding agents, emulsifiers, and stabilizers in the food industry. While their biological functions aren’t well known, they have attracted much attention for functional foods and pharmaceutical products.
In one research area, as published in the International Journal of Biological Macromolecules, an exopolysaccharide that was isolated from tofu (a product of Lactobacillus plantarum) induced secretion of nitric oxide and enhanced the macrophages’ phagocytic potential. That also increased the IgA concentration in the mucosa of the intestines and stimulated the proliferation of lymphocytes.
Exopolysaccharides may inhibit cholesterol absorption and have a significant effect on lipid metabolism as well. Additionally, exopolysaccharides from Lactobacillus bacteria isolated from Durian fruit that has been fermented were found to have antimicrobial and antioxidant properties, as per the journal Molecules.
A class of EPSs called β-glucans can interact with specific receptors on macrophages surface area and activate them, enhancing the body’s immune response. This can increase the absorption of carotenoids or those agents that have anti-inflammatory and antioxidant properties, claims research in Molecular Nutrition and Food Research.
Enzymes such as glutathione peroxidase (GPx), catalase, peroxide dismutase (SOD), and NADH-oxidase are some of the antioxidant enzymes that play a role in defending against reactive oxygen species.
Two strains of Lactobacillus fermentum have high concentrations of glutathione peroxidase, according to the Journal of Agriculture and Food Chemistry. They have been shown to have potent antioxidant properties. On the other hand, Lactobacillus Plantarum was studied and shown to have increased glutathione peroxidase properties in serum.
There have been trials that show that the Lactobacillus anti-inflammatory activities depend on the antioxidative enzyme expression of each of the strains. However, there is more data that is needed regarding sole antioxidant enzyme usage.
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Biologically active metabolites that are secreted by bacteria are contained in cell-free supernatants.
These are obtained from cell cultures, and after a period of incubation, the microbes are then removed after centrifuging. These metabolites are produced from different microorganisms and have different activities.
Both Lactobacillus acidophilus and Lactobacillus casei supernatants have been shown to have antioxidant and anti-inflammatory properties on neutrophils, macrophages, and epithelial cells in the intestines, according to Evidence-Based Complementary and Alternative Medicine.
Both Lactobacillus and Bifidobacterium supernatants were shown to potentially act as a promising treatment of diarrhea for their display of preventing enteroinvasive E.coli from invading enterocytes as well, says a study in the Journal of Infection and Chemotherapy.
Some research in the journal Nutrients suggests they may have a local effect on the protective gene expression and the intestinal environment, and some studies claim they act as promising anti-infection agents.
While most clinical trial testing and research have been done on bacteria, there is encouraging news for the supernatants derived from yeast.
Cell Wall Fragments
Bacterial lipoteichoic acid is a component of the bacterial cell wall that can give a specific immune response.
This acid, also known as LTA, is a cell wall fragment found in Gram-positive bacteria. It has ambiguous scientific data but has been shown to have some immunostimulatory effects. says the Journal of Inflammation.
Lipoteichoic acid in a topical application does enhance the release of anti-infectious peptides, especially the bacteria from the Lactobacillus and Bifidobacteria genera. Those genera of bacteria were shown to give off significant amounts of LTA and induce skin mast cell responses against viral and bacterial infections, according to The Lancet.
Overall, further evaluations on the LTA and its use as an anti-inflammatory agent are needed.
Obtained through a mechanical or chemical degradation of Gram-negative and Gram-positive bacteria, bacterial lysates are used clinically to connect the intestinal immune system and the respiratory system.
Studies have shown that bacterial lysates given orally activate T and B lymphocytes in the small intestine Peyer’s patches. These mature lymphocytes will then go to the respiratory tract’s mucous membranes and promote IgA secretion, according to the International Journal of Immunopathology and Pharmacology.
Many research studies have also been done on the safety of using bacterial lysates for recurrent upper respiratory infections.
A 2018 analysis in ERR showed that when 4800 children were studied, there was a lower incidence of respiratory infection in those who received bacterial lysates than those in the control group.
A 2020 review in the European Respiratory Review also showed the effectiveness of bacterial lysates for reducing asthma exacerbation and wheezing frequency in children. It is a natural parallel to provide bacterial lysates for those with asthma, chronic obstructive pulmonary disease, and other respiratory conditions.
Heat killed Lactobacillus paracasei was able to reduce symptoms of dry eye when put into a research study. More bacterial lysates like this will be studied for broader reaching treatment options, as published in Nutrients.
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Gut microbiota is responsible for aromatic amino acid production, vitamin molecules, and phenolic-derived metabolites. They are essential factors in the microbiome for their high bioavailability and their antioxidant features.
Intestinal bacteria can produce folate, which plays a vital role in DNA synthesis and as an antioxidant. There are countries with mandatory folate fortification for their food. These countries have shown a lower risk of certain health conditions per capita than those without the mandate.
Microbiota in the intestinal tract is involved in aromatic amino acid metabolism. As bioactive molecules, aromatic amino acids act on organs such as the brain, kidneys, and cardiovascular system.
The symbiosis between gut microbiota and dietary polyphenols helps form the basis for a metabotype. Metabotyping is the relationship between gut microbiome-derived metabolites and a metabolic phenotype that provides the rationale for “personalized nutrition.”
Because of this, paraprobiotics that are derived from polyphenols such as urolithin A (UA) can have anti-obesity effects and lowered insulin resistance, according to PLoS Biology.
Short-Chain Fatty Acids
A product of plant polysaccharide fermentation, short-chain fatty acids are well known. Acetic, butyric, and propionic acids can form fatty acid salts acetate, butyrate, and propionate.
Butyrate is an energy source for enterocytes, helps renew intestinal epithelium, and has been shown in studies to have immunosuppressive effects and increases cytokine expression to induce food tolerance. It can also, by inhibiting histone deacetylases, modulate gene expression, says research in Frontiers in Immunology.
Short-chain fatty acids affect energy management by the secretion of glucagon-like peptide 1 and stimulating G-protein coupled receptors. Increasing fecal and serum acetate did show an increase in insulin sensitivity and lowered body fat. Frontiers in Endocrinology says acetate is also demonstrated in several studies to regulate appetite in the central nervous system.
Propionate is the primary substrate of liver gluconeogenesis and plays a role in carbohydrate metabolism. It also has a statin-like effect that may lower the cholesterol pathways, according to the British Journal of Nutrition.
Propionate is also comparable in anti-inflammatory activity to butyrate. Several new studies are currently being done to see the therapeutic effects of short-chain fatty acids in the roles they may play in future medicine.
Spotlight on Postbiotic Short-Chain Fatty Acids
Perhaps the most important out of all those class types of paraprobiotics is the short-chain fatty acid.
This metabolite is a weak acid that creates the optimal acid-base balance in your gut. According to Trends in Food Science & Technology, when you have gas, bloating, inflammation, diarrhea, or other gastrointestinal problems, the acid-base balance is out of sync, which is called dysbiosis.
During dysbiosis the acid-base balance can be up to 100 times too alkaline. Bringing the gastrointestinal tract back into good gut health needs these short-chain fatty acids from probiotic bacteria, based on research published in the journal Inflammatory Bowel Diseases.
Anytime the body’s intestinal flora is that far out of balance, whether it is too alkaline or too acidic, there will be distress.
Gastrointestinal tract cells have one of the fastest turnover rates, with people creating an entire new digestive tract every week or so. There is a lot of energy that goes into that generation of cell growth, and that energy doesn’t come from your blood supply; it comes from short-chain fatty acids, according to Sage Veterinary Pathology.
These short-chain fatty acids feed or energize the cell growth so that your digestive tract can renew itself and replicate. Without them, there are going to be problems with the regeneration.
You can see that short-chain fatty acids have a tremendous role in your entire body’s health. They are perhaps the most important class of all the paraprobiotic classes, one that should be well-watched and studied for future applications.
Benefits of Short-Chain Fatty Acid Butyrate
Benefits to butyrate include regulating constipation/diarrhea, balancing the intestinal microbiota, strengthening the intestinal mucosa integrity, strengthening epithelium, improving intestinal barrier function, and having immunomodulating, anti-inflammatory activity.
Diets that are rich in vegetables contain fiber, and more short-chain fatty acids like butyrate are produced in the intestines. Low nutrient diets that lack vegetables may lead to a deficiency, causing problems like allergies, dysbiosis, inflammation, and increased intestinal permeability.
Differences: Probiotics, Prebiotics, Synbiotics, and Postbiotics
There are so many retail products coming to the markets today, all with the trendy ‘wellness’ category, trying to be the next big thing, and some of these products are the -biotics family.
If you are browsing, you’ll see all types of new terms like synbiotics and paraprobiotics. They all sound the same, but they aren’t. They combine precisely, but what are the differences between probiotics, prebiotics, synbiotics, and paraprobiotics?
Defined in 2001 by an Expert Panel of the FAO/WHO (Food and Agricultural Organization and the World Health Organization), the definition of probiotic changed slightly in 2013 by the ISAPP (International Scientific Association for Probiotics and Prebiotics) to become “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.”
Probiotics are designed to help our intestinal flora health and our immune system. While our bodies are supposed to have these ‘good bacteria’ already in our systems, there is so much in today’s world that can strip them to unhealthy levels, creating an imbalance in the body.
Greek yogurt is an excellent source of probiotics, as are foods like kimchi, sauerkraut, and kombucha. Fermented foods are excellent for gut health and they may just help you lose weight, up-and-coming research suggests. Check out the Noom free trial offer today and start learning more about how to choose the best foods for your gut and your waistline!
The concept of prebiotics was first introduced by Marcel Roberfroid and Glenn Gibson in 1995. According to Foods, it was defined as a “non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, thus improving host health.”
Prebiotics are found in certain foods like onion, chicory root, and asparagus and are non-digestible carbohydrates. Since our bodies aren’t equipped to break down the fibers in prebiotics, it fuels our gut and encourages good bacteria growth in the gut.
Synbiotics were defined in May of 2019 by the ISAPP as “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host,” according to a scientific publication in Nutrition Reviews, Gastroenterology & Hepatology.
When probiotics and prebiotics combine, it creates synbiotics. While there are no specific health benefits of synbiotics, there are benefits from the particular combination of prebiotics and probiotics.
Postbiotics do not have a formal definition yet. Still, experts and researchers have stated that they are “bioactive compounds produced by food-grade micro-organisms during a fermentation process. Paraprobiotics include microbial cells, cell constituents, and metabolites,” according to the International Journal of Molecular Sciences.
Paraprobiotics include functional peptides and proteins, microbial cell fractions, cell lysates, extracellular polysaccharides, short-chain fatty acids, and teichoic acid. In some papers, paraprobiotics are called metabiotics, which is defined as “soluble factors secreted by live bacteria or released after bacterial lysis, which confer physiological benefits to the host,” according to a study in Microorganisms.
Symbiosis Between Probiotics, Prebiotics, and Paraprobiotics
The latest research shows that what we thought were positive effects of probiotics may be postbiotic effects on the body and gut flora. However, the symbiosis between prebiotics, probiotics, and postbiotic effects are needed in tandem. Prebiotics come before probiotics, which in turn come before postbiotic processing.
If prebiotics are food, then probiotics are the microorganisms that consume that food, and the probiotic waste is postbiotic aftereffects. These three processes combining is what keeps our body in a state of balance.
It is good to keep in mind that prebiotics and probiotics are live bacteria while postbiotic bacteria are dead. They work together to give the body a healthy immune system and optimal gastrointestinal tract health.
Where Can You Find Paraprobiotics?
As paraprobiotics are a part of the probiotic fermentation process, the source of paraprobiotics is probiotics themselves. Foods that have a fermenting process are going to be high on the list.
Foods that increase the number of paraprobiotics in the body are:
- Miso soup
- Soft cheeses
- Sourdough bread
Paraprobiotics can also be delivered by pills derived from lab-produced extraction processes. For those that do not eat a lot of fermented food, supplementation through this method may be the best way to increase the gut health benefits of paraprobiotics.
There are several supplement options on the market, and many are combined with prebiotics and probiotics so that you get all three in one. This combination of -biotics has been shown to increase gut flora health and build up immune system response.
Paraprobiotics and Fermentation
During fermentation, microbes will act on individual ingredients to produce specific compounds to the microbe and the final product.
For example, acetobacteria will give you acetic acid, the acid that is found in vinegar. Yeasts will produce both the carbon dioxide and the alcohol found in beer. Propionibacterium freudenreichii will produce the taste that is found in Swiss cheese.
As you can see, that fermentation is a process that will give you different outcomes depending on the microbe and what it is acting upon.
When there is a conversion of unsaturated fatty acids to conjugated linoleic acids, it will enhance nutritional value. Live microbes in the fermentation process also increase the bioavailability of several vitamins and minerals while reducing antinutrients.
The biologically active compounds that are produced by the fermentation process are considered paraprobiotics. Fermented foods are not additionally processed past the fermentation process deliver both the live microorganisms that produce paraprobiotics.
Bacteria that are in the gut of those that are healthy are known as native, or commensal, bacteria. They are typically a combination of several microbes such as Enterococcus, Lactobacillus, Bacteroides, and Faecalibacterium and are similar to the types of fermentation bacteria and their byproducts give similar benefits.
What Health Benefits Are Associated With Paraprobiotics?
Paraprobiotics have several potential health benefits, including having properties of antioxidants, antiproliferatives, hypocholesterolemics, anti-inflammatories, immunomodulatories, antiobesogenics, and antihypertensives. In addition to these, they improve gut barrier function and boost the immune system.
According to the National Center for Complementary and Integrative Health, antioxidants are “ man-made or natural substances that may prevent or delay some types of cell damage.” They can be human-made or natural.
Antioxidants slow or prevent cell damage caused by free radicals, the unstable body-producing molecules made in reaction to environmental pressures. Endogenous antioxidants are made in the body, and exogenous antioxidants are made outside of the body.
If the body is unable to remove free radicals, cell and body harming oxidative stress can occur. Smoking, UV exposure, and pollution are some of the ways free radicals can be increased. Antioxidants serve to neutralize these free radicals.
Did you know exercise increases the body’s production of free radicals? Exercise is critical for weight loss and overall health, making postbiotics, and the antioxidants they contain, even more important. Once you learn how to choose the best foods for weight loss and gut health, you’ll find lasting, permanent change. Check out Noom today. You get a free trial offer for being a Dietsupplement reader.
Hypocholesterolemics are substances that may lower the blood cholesterol levels. They can be human-made or natural.
Anti-inflammatory agents are useful for helping the treatment of pain caused by slow tissue damage as a result of inflammation.
Inflammation that is chronic in the body can damage organs and blood vessels. Anti-inflammatories help fight this inflammation to aid in healthy healing.
While modulating the immune system, these help the body keep on guard for fighting infection. It is used for body defense.
These substances help counter the body’s ability to gain weight. This can be through better insulin regulation, lowering inflammation and water weight, and counteracting certain chemical production.
Other key health benefits of paraprobiotics include the following:
- Removes bad bacteria and promotes good bacteria, giving a gut microbial balance.
- Postbiotic metabolite ‘muramyl dipeptide’ can help those with insulin resistance by increasing insulin sensitivity, thus relieving glucose intolerance.
- Gives those with immunodeficiencies that cannot tolerate probiotics and infants a viable alternative.
- ‘Muramyl dipeptide’ may prevent obesity by increasing insulin sensitivity.
- Effective treatment of diarrhea because of the metabolic products released by probiotics (paraprobiotics).
- Populates the gut with good bacteria, helps fight infection, has antimicrobial properties.
- Reduces inflammation in those with inflammatory bowel disease in which probiotics may not be a benefit.
Paraprobiotics and Leaky Gut Syndrome
Leaky gut syndrome has the symptoms of cramping, aches, bloating, gas, and food sensitivities. While a bit of a medical mystery, the condition isn’t a medical school taught diagnosis and is often used as a placeholder. At the same time, additional tests are run for a different diagnosis.
Sometimes, however, there is no additional diagnosis, and the real cause is left unknown. Those with chronic symptoms without a cause are usually said to have leaky gut syndrome.
Possible causes for leaky gut syndrome are increased intestinal permeability, which can happen when the gut’s junctions that control what will pass on through the small intestine lining do not work correctly. Some items pass through due to this increase in permeability that shouldn’t, disrupting the balance and causing symptoms and damage, says research in Frontiers in Immunology.
This digestive tract mucous lining penetrability allows pathogens and toxins to get into your bloodstream and will give health problems such as digestive issues. Securing the penetrability ensures toxins and pathogens do not cross into the bloodstream.
Research is now suggesting that paraprobiotics could be a key in helping to relieve leaky gut syndrome. Clinical study of butyrate in the World Journal of Gastroenterology, a paraprobiotic, showed the ability to restore the intestinal lining and improved symptoms in those with gastrointestinal issues.
Paraprobiotics and Obesity
The paraprobiotic of muramyl dipeptide lowers adipose inflammation in obese mice, a study in Cell Metabolism showed. McMaster University’s Joseph F. Cavallari examined the role of muramyl dipeptide in obese mice, injecting them to see what benefits came from it.
They found that injecting the muramyl dipeptide glucose intolerance and lowered adipose inflammation. The obesity correlated with a reduction of insulin resistance, which could mean that these paraprobiotics could help regulate insulin in the body of obese humans as well.
While there are no deep clinical studies thus far on the use of paraprobiotics specifically for weight loss or reducing obesity, there are some anecdotal findings in that paraprobiotics can help specific areas that can have weight loss as a result.
Those that have bloating and weight gain as a result of insulin resistance, for example, may have some weight loss once that insulin resistance is managed and treated through paraprobiotics.
Side Effects and Risks of Paraprobiotics
While paraprobiotics are generally safe, there can be some unpleasant side effects for sensitive gastrointestinal systems. Adding postbiotic foods or supplements for those individuals may have some gastro disturbances such as gas, constipation or diarrhea, stomach upset, and bloating.
Most of these are temporary and will lessen in severity or go away entirely once your body has acclimated to the bacterial balance again in your gut. Anytime there is a flux of bacteria, whether good or bad, your intestinal response will come back with these types of symptoms.
These are typically mild, but if they start to impact your life, you can talk with a healthcare provider about altering your supplementation.
Future Clinical Applications of Paraprobiotics
As postbiotics shape microbiota structure and tighten the gut barrier, playing a role in immune system maturation, paraprobiotics have possibilities of future treatments of conditions where effective causal therapy has not been seen.
Clinical trials for paraprobiotics are already underway for their use in inflammatory bowel disease, multiple sclerosis, and Alzheimer’s disease.
Future applications can go further in using paraprobiotics in pediatrics and using the proper microbiota structure in the first months of life. For all applications where probiotics are not utilized (pediatrics, immunocompromised, etc.), paraprobiotics can pick up the torch and be used as a possible treatment option.
While we continue to unwrap and process all forms of microbiota and their link to each of our health systems, our gut microbiota can be altered by consuming prebiotic and probiotic foods and supplements to create paraprobiotics. The benefits of offering a specific set of bacteria through supplements can give you a beneficial effect and help prevent gut dysbiosis, creating a more calm and balanced gut flora.
Perhaps in the future, medicine will combine a personalized approach to gut health by analyzing the patient’s flora and synthesizing a precise plan to keep their body in a state of balance, but until then we can get out there and try new foods with gut-healthy probiotics, prebiotics, synbiotics, paraprobiotics, and postbiotics.
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