PROBIOTICS, PREBIOTICS, SYNBIOTICS AND POSTBIOTICS. AS USEFUL AS CLAIMED?

ABSTRACT

With increased awareness of the gut-brain axis and the importance of gut health, there has been an increase in the desire for clear information on biotics.  The gut-brain axis is thought to influence a variety of essential physiological systems, including neurotransmitters, the immune system, and hormones, emphasizing the importance of this topic.  Probiotics, prebiotics, synbiotics, and postbiotics are all examples of biotics.  In general, biotics are assumed to protect and promote healthy gut health by inhibiting pathogen colonization.  Each form of biotic has a unique mode of action and function, and can be found in a variety of dietary products or within the human body.  Furthermore, each subcategory of biotics contains a variety of species and gene sequences, making it impossible to determine if biotics as a whole or separately provide a panacea for overall health.  Despite this, the research advises that understanding precise dosage, strain, and evidence on efficacy is essential to create an informed opinion on how biotics can aid in the maintenance of a healthy gut microbiota and the prevention or treatment of various diseases and disorders.

INTRODUCTION

Gut health has garnered growing attention during the last decade.  The gut microbiome is a complicated organ system that contributes to a variety of physiological functions such as neurotransmitters, the immune system, and hormones (Quigley 2013).  The gut-brain axis is a bidirectional relationship known to occur between the intestinal and central nervous systems that is deemed essential due to the probable association with the host’s health status (Li et al. 2020).  The gut microbiome is made up of 100 trillion living bacterial microorganisms that can be classified as ‘good’ or ‘bad’. These ‘good’ and ‘bad’ microbes maintain gut homeostasis and act as anti-inflammatory, antibiotic, anti-diabetic, and anti-carcinogenic agents (Haseeb et al. 2019).  Figure 1 shows one example.  Probiotics, prebiotics, synbiotics, and now postbiotics have been proven in a number of evidence-based clinical trials to have favorable impacts on health and wellness due to their protective and promotive properties on the gut microbiome (Yadav et al. 2022).  However, the question remains as to how they assist our microbiome and whether supplemental versions of these biotics are required to preserve and promote good gut health, specifically by preventing pathogen colonization. This article will address these concerns by outlining the four categories of biotics available, their relationship to the gut flora, and summarizing the data.

 

Figure 1. Structure of the microbiome gut-brain axis (image based on Rogers et al. 2016)

HEALTH OF THE GUT

The ‘good’ bacteria in your gut perform a variety of critical homeostatic activities, including:
– Metabolic role in which the bacteria salvages calories, generates short chain fatty acids, synthesizes arginine and glutamine, synthesizes vitamin K and folic acid, and aids in medication metabolism
– Bile acid deconjugation
– Pathogen colonization prevention; and
– Immunologic effects by stimulating IgA synthesis, regulating anti-inflammatory and proinflammatory cytokines, and inducing regulatory T cells (Quigley 2013).

Microbiota equilibrium is generally maintained by peristalsis (intestinal motility) and the antimicrobial actions of bile, pancreatic and intestinal secretions, gastric acid, the stomach, and the proximal small intestine (Quigley 2013).  This, however, can be interrupted if ‘bad’ or harmful bacteria are introduced on a frequent basis.  These bad bacteria can multiply and colonize, so taking over or reducing the benefits of the good bacteria.  Furthermore, a number of studies have indicated that some antibiotics, particularly those given to children, might cause irreversible alterations to the microbiome (Haseeb et al. 2019; Li et al. 2020).  Less study has been undertaken on the impact of pesticides on the microbiome; nevertheless, with increased pesticide use worldwide, this is an area of interest that warrants additional inquiry (Giambo et al. 2021).

The gut and the body have a symbiotic relationship, which means they rely on one other to thrive.  Clinical studies have shown a link between a variety of illnesses and imbalances and a healthy or unhealthy microbiome, including obesity, type 2 diabetes, cardiovascular disease, inflammatory bowel disease, anxiety, depression, rheumatoid arthritis, and colon cancer (Kennedy et al. 2014; Zhang et al. 2015; Aron-Wisnewsky and Clement, 2016; Rogers et al. 2016). Within these research, but not limited to, probiotic, prebiotic, synbiotic, and postbiotic consumption through food sources and supplements has gained traction.  Evidence suggests that biotics have a favorable influence on the microbiome, resulting in a reduction in disease and illness.  Despite this, there is still a lack of information about where to get them in meals and supplements, how they work, and their overall advantages.  This could be due to a variety of factors such as the use of Latin genus names, which make it difficult to recall, the complexity of qualities, dose and storage needs, and/or inadequate assessment in controlled studies.  Furthermore, while most supplements are meant to transport highly specific species of bacteria to the gut, not all supplements contain the same and/or appropriate quantity or quality of bacteria.  As a result, understanding the what, why, how, and when is essential.

PROBIOTICS

Let’s start with probiotics. The term probiotics is derived from the Greek word ‘for life’ (Pandey et al. 2015).  Probiotics may regulate host immunity by protecting and promoting healthy gut microbiota (Yadav et al. 2022).  The mechanisms of action known to explain the protective qualities of probiotics on gut health include good bacteria colonization, the production of inhibitory substances such as short-fatty acids, and finally acting as competitors on the intestinal epithelial surface by blocking adhering sites and reducing pathogen interaction (Yaduv et al. 2022).

Probiotics have been ingested since ancient times through fermented foods such as:
• Yogurt
• Kefir (both dairy and nondairy);
• Sauerkraut
• Kimchi
• Miso;
• Kombucha, as well as
• Pickled cucumbers (unpasteurized).

The following probiotic strains are the most regularly consumed:
– Bacillus coagulans;
Lactobacilli are bacteria.
Streptococcus aureus;
Saccharomyces cerevisiae;
– S. boulardii, as well as
– B. coagulans.

However, new strains and genera of probiotics are constantly appearing as a result of fresh scientific advances (Pandey et al. 2015).

Each probiotic species has a unique effect on the body, and products may contain a single strain or a blend of strains with varying benefits.  It is typical to see the probiotic species name paired with the genus name in food and on labels.  Bifidobacterium, for example, is often found in supplements and food sources and is marketed to strengthen the immune system, aid in the breakdown of lactose into nutrients, and prevent the formation of dangerous bacteria (Pandey et al. 2015).  The genus Bifidobacterium is usually abbreviated as B. is written as B.animalis when paired with an individual species name such as animalis.  Yogurt contains B.animalis, which is expected to assist digestion and protect against food-borne bacteria (Yadav et al. 2022).   Bifidobacterium breve is another typical Bifidobacterium combination that is naturally found in the digestive system and vagina and has infection-fighting and nutrient-absorbing characteristics, as well as assisting in the breakdown of plant fibers (O’Callaghan and Van Sinderen 2016). At the same time, B.longum, which is naturally abundant in the gastrointestinal system, is an antioxidant that aids in glucose breakdown (O’Callaghan and Van Sinderen 2016).

Lactobacillus is the second most prevalent probiotic genus that produces lactase; lactase is an enzyme that degrades lactose and creates lactic acid, which is known to suppress harmful bacteria (Pandey et al. 2015).  Lactobacillus is found naturally in the mouth, small intestine, and vagina, as well as in foods such as yogurt and fermented soy products.  The two most common species among the twenty-five genera are L. Acidophilus has been shown to aid digestion and fight vaginal bacterial and L. reuteri is also known to aid digestion and reduce oral bacteria that cause tooth decay (Zhang et al. 2015).  With further understanding of the human microbiome and the benefits of probiotics, the future of next-generation supplements is within reach.  For instance, L. plantarum can be found in yacon root, dragon fruit, and F. prausnitzii discovered in green algae, seaweed, and mushrooms are only a few examples of new probiotics being researched (Panday et al. 2015).

The strongest clinical evidence for probiotic usage is in the treatment of acute diarrhea caused by rotavirus and pouchitis (Guandalini et al. 2000; Van Niel et al. 2002; Canini et al. 2007).  In the treatment of antibiotic-associated diarrhea, Clostridium difficile infection, and travellers’ diarrhea, there is similar but sometimes contradictory evidence (Williams 2010).  Irritable bowel syndrome (IBS) which is usually accompanied with bloating, flatulence, disturbed bowel habits and abdominal pain and assumed to be a result of a bacterial overgrowth in the small intestine has attracted a lot of interest in relation to probiotics.  A number of studies have demonstrated that probiotic strains Lactobacillus and Bifidobacterium strains or the combination product VSL#3 can help with IBS symptoms (Williams 2010).  Probiotic efficacy studies have drawbacks such as a lack of strand standardization, dosage provided, clinical outcomes assessed, and treatment durations (Williams 2010).  Other diseases and conditions which indicate some benefit although still remain under discussion due comparable study constraints noted above include ulcerative colitis, vulvovaginal candidiasis, Chron’s disease and some allergies (Williams 2010).

New and improved probiotics offer a promising therapy option for a variety of infectious and non-infectious disorders, but more research and knowledge of the complicated molecular pathways is required to generate successful probiotic compositions.  Furthermore, there are certain obstacles for probiotic formulations, such as the incorrect use of the term probiotics and the significance of strain specificity (Pandey et al. 2015).  Probiotics are considered nutritional supplements in many countries and hence do not have to meet the regulatory standards of pharmaceuticals.  Therefore, it is recommended that when selecting probiotics, the following guidelines and indications be followed; clear strain identification present, functional characterisation of strain(s) with clear evidence of health benefits in human studies and honest labelling of efficacy claims (Pandey et al. 2015).

PREBIOTICS

Prebiotics are also often touted as encouraging good gut health and improving immune system response.  They are described as substrates which are selectively exploited by host bacteria resulting in a health advantage (Davani-Davari et al. 2019).  Prebiotics are generally short-chain carbohydrates found in food sources that escape the process of digestion and are utilized to assist probiotics move through the upper gastrointestinal tract (Yaduv et al. 2022).  Ideal prebiotics fibres are assumed to be resistant to the acids found in the stomach, bile salts and other intestinal enzymes; they should not be absorbed in the upper gastrointestinal tract and lastly be easily fermentable (Holscher, 2017).  Further desirable qualities also include that they are active at a low dose, have little side effects, have changing viscosity and have the potential to govern microbiota modulation (Pandey et al. 2015).

Prebiotics that are commonly studied include:
– Fructooligosaccharides;
IMO (Isomalto-oligosaccharides);
– Xylosaccharides (XOS);
– Inulin, as well as
– Pectin.

Prebiotics can be found in a variety of vegetables, including:
– Onion (FOS, inulin)
– Inulin (asparagus)
– Inulin (garlic)
– Inulin-rich chicory root
Inulin (Jerusalem artichoke)
– Oatmeal (fibre)
– Wheat (a source of fiber)
– Green/unripe bananas (fibre)
– Yacon (both IMO and FOS)
– Dragon fruit (in my opinion)
– Miso (in my opinion)
– Soy sauce (in my opinion)
– Honey (both IMO and XOS)

Prebiotics are thought to enhance Bifidobacterium proliferation and Lactobacillus species, as well as reducing the quantity of gram-positive and gram-negative bacteria in the colon (Nobre et al. 2022). Other health benefits include improved local and systemic immunological response, greater mineral absorption, improved responses to allergic activity, and reduced symptoms of gut illnesses such as IBS and Chron’s disease (Nobre et al. 2022).

Despite mounting evidence emphasizing the therapeutic effects of prebiotics, particularly when combined with probiotics, obstacles persist.  To begin with, manufacturing of prebiotics outside of natural food sources remains difficult due to extraction and time-consuming multistep downstream processes (Nobre et al. 2022).  Furthermore, evidence-based research establishing the precise microbiologic, physiologic, and biochemical pathways is still understudied, with requests for long-term clinical trials and genetic research to back up their therapeutic claims (Davani-Davari et al. 2019).

SYNBIOTICS 

Understanding probiotics and prebiotics would lead one to believe that synbiotics are simple (Pandey et al. 2015).  However, Yadav and colleagues (2022) divide synbiotics into two categories: complimentary and synergistic.  Complementary synbiotics are the most well-known synbiotics, and they include both a probiotic and a prebiotic, both of which offer one or more health benefits for the host but are not co-dependent. Synergistic synbiotics, on the other hand, do not need to expressly contain a probiotic and prebiotic, but rather a substrate that is designed to be selectively utilized by the co-administered organism (Swanson et al. 2020).  It is acknowledged that nearly all clinical trials reporting on synbiotics benefits to human health are of the complimentary variety, whereas synergistic synbiotics remain unstudied to date (Swanson et al. 2020). Synbiotics were initially created to help probiotics overcome survival challenges such as decreased efficacy due to factors such as pH, hydrogen peroxide, moisture stress, and organic acids (Pandey et al. 2015).  Thus, the argument for synbiotics is predicated on better postbiotic survivability during their travel through the upper digestive tract.  Despite some confusion about synbiotic classification, available evidence suggests that synbiotic foods and supplements promote host health and nutrition by increasing the number of probiotic bacteria and digestive enzymes such as lactase, lipase, sucrase, and isomaltase (Yang et al. 2005).  Short-term synbiotic supplementation was recently reported to be statistically effective in decreasing metabolic syndrome signs when compared to placebo treatment (Cicero et al 2021).  Obesity, high cholesterol, high glucose levels, and hypertension are metabolic syndrome components that are linked to coronary heart disease and cerebrovascular illness (Cicero et al. 2021).  Synbiotics, both complementary and synergistic, offer considerable potential in this field of health, particularly when combined with the anticipated novel pro and prebiotics in the future; however, more research is needed.

POSTBIOTICS

Postbiotics are likely the newest subset of biotics, with rising studies indicating favorable health benefits. Postbiotics are bioactive chemicals formed as a result of probiotic bacteria interacting with prebiotics, such as fiber present in the colon (Jay et al 2022).  Despite being considered microbial byproducts, the effects of these interactions after digestion have shown a lot of positive results (Jay et al 2022).  These include the manufacture of:
– Fatty acids with a short chain, such as butyrate, acetate, or propionate;
– Polysaccharides;
Exopolysaccharides are a type of polysaccharide.
– Extraneous;
– Fragments of cell walls
Bacterial lysates are a type of lysate.
– Enzymes, as well as
– Amino acids and vitamins

However, like with any by-product, there is a possibility that not all have positive features.  Bile acids, for example, are hazardous postbiotics created as a result of excessive consumption of high-fat diets (Ridlon et al. 2014).  Because of their pro-inflammatory and potentially pathogenic qualities, bile acids have been shown to affect healthy gut microbiota functioning (Ridlon et al. 2014).
Postbiotics have recently received interest due to their association with cancer development and treatment.  A number of postbiotics, also known as gut microbial metabolites, are rigorously assessed in a recent study, indicating both carcinogenic and anticancer effects (Jaye et al. 2022).  Postbiotic activity has been linked to increased bile acids as a result of high protein and low carbohydrate diets, whereas short-chain fatty acid postbiotics have shown to have cancer-protective properties during fibre fermentation properties (Jaye et al. 2022).  This was shown in a clinical investigation of colon cancer patients who had lower amounts of short chain fatty acids in their intestines than healthy volunteers (Yusef et al. 2019).  This observation was replicated in premenopausal breast cancer patients with reduced levels of short-chain fatty acid generating bacteria (He et al. 2021).  These findings support the necessity of healthy microbiota in the gut for health; however, due to the novelty of postbiotics, more research is needed to back up these statements.  This will provide guidance on what to avoid and/or supplement in both preventative and therapy settings.

Nisin is a postbiotic with cytotoxic characteristics in colorectal cancer and head and neck squamous cell carcinoma (Ahmadi et al. 2017).  Its mechanism of action is assumed to be the induction of apoptosis, or programmed cell death (Ahmadi et al. 2017).  Apoptosis is important in cancer prevention since it is utilized to clear the body of undesired cells and, if not performed, can result in uncontrolled cell division and the growth of tumor/s. Another postbiotic metabolite generated from the amino acids phenylalanine and tyrosine after ingestion of plant-based foods is phenylpropanoid-derived metabolite.  It has also been proven to have anti-inflammatory and antioxidant capabilities, as well as to prevent the proliferation of many cancer cell types.  Postbiotics have also been demonstrated to benefit the immune system.  Butyrate, a short-chain fatty acid, for example, can stimulate regulatory T cells in the gut, whereas cell wall fragments can enhance cytokines that help to reduce inflammation and promote immunological responses (Zókiewicz et al. 2020).

Postbiotics, like the preceding biotics discussed in this work, have a significant degree of heterogeneity, making it difficult to summarize their specific mechanism of action and properties (Zókiewicz et al. 2020).  However, research suggests that postbiotics have multiple qualities that interact together to produce anti-inflammatory, immunomodulatory, antioxidant, and anti-cancer activities (Zókiewicz et al. 2020).  It is emphasized that due to non-specific trials, the precise postbiotic impact has not been examined, and that more research is needed.

CONCLUSION

Overall, the importance of appropriate microbiota, and the effect it has on human health and wellbeing has been established in this review.
The gut-brain axis is thought to influence a variety of essential physiological systems, including neurotransmitters, the immune system, and hormones, emphasizing the importance of this topic.  A well-balanced diet and exercise are the basic concepts for excellent microbiota and overall health, which should be emphasized throughout and as a take-home message.

However, when an imbalance emerges, additional biotics may be beneficial in restoring and promoting healthy microbiome features.  Each of the biotics described has unique qualities that may be beneficial for particular diseases and ailments.  However, current research reveals that biotic treatments are still specialized to specific diseases and disorders, and it cannot be inferred that biotics, as a whole or individually, constitute a magic bullet to overall health.  According to this review, understanding specific dosage, strain, and evidence on effectiveness is necessary to ensure informed action is made.  As a result, answering the question of whether it is required to take supplemental types of biotics to maintain and promote good gut health, specifically by preventing pathogen colonization, is not so simple. Only up to 10 strains are currently available on the regular market.  Knowing we have hundreds of different strains circulating, we might even be increasing levels of certain strains which we have no shortage of, as such, distrubing the microbiome even more.  Additional studies are needed to address the nitty gritty of effectiveness and treatment alternatives, and with new biotics being discovered and global interest in the topic, it is thought and hoped that the answers we seek will be supplied using evidence-based science sooner rather than later.

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