Prebiotics and Probiotics

The human microbiome consisting of the trillions of bacteria that reside in our GI tracts, on our skin and in our oral cavity, is a source of valuable insight into our health and vulnerability to developing certain disease conditions.  As a result, the market for supplemental bacteria in the form of probiotics has continued to grow.  According to the Global Probiotics Market Report from MarketWatch.com, the probiotics market is currently (2019) valued at USD 42.55 billion and is projected to reach USD 74.69 billion by 2025, at a CAGR of 7.3% during that timeframe. [1]

There are over 500 species of bacteria residing in the typical healthy human GI tract (and even more if strain differentiation is considered).  Very few of these can be found in the stomach or upper small intestine because of the influence of gastric acid.  Colonization gradually increases throughout the small intestine.  But by far most bacteria reside in the colon. 

Initially, most probiotic species were the same types of bacterial species that are naturally found within the GI tract.  The use of indigenous species helps ensure colonization in the intestinal environment.  These probiotic bacteria provide benefits through competitive inhibition, as they compete with undesirable bacteria for space within the intestinal tract. This is especially critical after an antibiotic regimen that destroys pathogenic bacteria but often at the expense of the resident beneficial bacteria.  It is now known that disruptions in the body’s microbiome can have profound effects on health, and that even medications such as antibiotics that may be life-saving can alter the makeup of the intestinal microflora and potentially contribute to the proliferation of undesirable or opportunistic microbial species such as Clostridium difficile or Candida species.  As a result, probiotic intake through fermented foods or supplementation has become a standard medical recommendation after an extended antibiotic regimen. 

Many commercial probiotics are designed to help promote efficient digestion.  Part of the function of a healthy microbiome is to produce digestive enzymes, enabling healthy digestion and absorption of critical nutrients.  For example, the enzyme lactase, necessary for the breakdown and intestinal absorption of the milk sugar, lactose, is produced primarily by intestinal epithelial cells in the walls of the small intestine; but it is also produced by certain intestinal bacteria, such as Lactobacillus bulgaricus and Streptococcus thermophilus.  Supplementing with a lactase-producing probiotic can help alleviate some of the worst symptoms of lactose intolerance.  In addition, we now know that certain probiotic species can help lower pH levels in the colon, potentially facilitating movement of stool through the colon and eliminating constipation.  Probiotics can also help relieve antibiotic-related diarrhea and can help with the absorption of protein, vitamins and minerals. [2]  Commercial probiotic supplements targeting general digestion are often of the Lactobacillus and Bifidobacterium genera. 

The other large category for probiotics is in the area of Immune support.  Not only can the right probiotic bacteria inhibit the growth and colonization of harmful invading bacteria by taking up all of the available space, but some probiotic bacteria may stimulate the body’s production of natural antibodies and boost immune cells, such as IgA-producing cells, T lymphocytes and natural killer cells. Lactobacillus acidophilus is known for its benefits in stimulating the gut-mediated immune response, and several proprietary strains of L. acidophilus are commercially available and backed by extensive research.  

It is now known that the immune benefits of the body’s protective microbiome don’t begin in the gut, but in the oral cavity, where pathogenic microbes most often enter the body.  The oral cavity is home to as many different species of bacteria, if not more, than the gut; and these bacteria can form an extremely strong barrier against invaders, influencing the health, not only of the teeth and gums, but extending into the throat and ear canals.[3]

To a certain extent, these good bacteria function through competitive inhibition, but more importantly, some strains of bacteria like the beneficial oral cavity species, Streptococcus salivarius, can produce compounds called Bacteriocin-Like-Inhibitory-Substances (BLIS).  These compounds are highly inhibitory to specific pathogenic bacteria.  Probiotics derived from indigenous strains of these beneficial bacteria can provide a front-line protection against pathogens entering the body through the mouth and nose.  Some of these strains, such as S. salivarius K12 have been extensively researched for safety and their ability to colonize in the human oral cavity, as well as their efficacy in preventing throat and middle infections.[4],[5],[6],[7],[8],[9],[10]

There are other BLIS producing strains of S. salivarius that are more active against pathogenic strains on the teeth and gums.  Persons who have these bacteria as normal occupants of their oral cavity are those who never seem to get cavities or have any periodontal issues.  Based on what we know now about the relationship between the health of the periodontal surfaces and the health of the entire body, these bacterial occupants can be critical for overall health, since the research is mounting that the health of the oral cavity is directly related to the health of the entire body, especially in the area of cardiovascular health.  Probiotic strains such as S. salivarius M18 have been shown to positively impact several areas of dental and periodontal health.[11] [12] [13]                                                                                                                                                                                                                                                                     

As the probiotic industry has evolved, so has the level of research into the mechanisms through which probiotics exert their influence on the immune system. One area that has been the focus of current research is in the production of short chain fatty acids (SCFA) within the colon. These products of bacterial fermentation appear to have broad positive influence, not just in the colon, but throughout the body. One recent study found that SCFA derived from gut microbiota metabolism play an important role in maintaining host immune composition and repair capacity after a heart attack.[14] Another very recent unpublished research has also demonstrated a dramatic benefit from select probiotic supplementation on the prevention of gastric damage caused by aspirin therapy.

As a result of the advances made in the benefits of probiotic supplementation, formulators and manufacturers have also focused attention on the stability of probiotics.  With their popularity has come the desire to put these living bacteria in a myriad of food and supplement formats.  Unfortunately, most of the bacteria that reside within our bodies are very susceptible to temperature, humidity and pressure – all of which are common forces within the manufacturing process.  Therefore, very careful attention must be given in providing the right manufacturing environment for survival.

Manufacturing processes that microencapsulate the live bacteria have become very sophisticated and can provide a way to ensure both shelf stability and survival through the acidic conditions of the gastric region to reach their target location in the intestines.  Some of the newer microencapsulation technologies can not only protect the live bacteria from heat and humidity in storage,  but also provide a coating that is invulnerable to the acidic conditions of the stomach, and can strategically release the bacteria when the pH rises, thus enabling viable numbers of probiotics to reach the optimal destination for digestive and immune system support.[15]

The desire to incorporate probiotics into more conventional food formats has also led to the rise of probiotics that are derived from spore-forming bacteria.  These bacteria have been shown to have some health benefits and they do have the advantage of survival, but there can be significant challenges for manufacturers because of their persistent nature.

Probiotics are not the only way to support a healthy gut microbiome.  Supplemental nutrient sources for the bacteria, or prebiotics, are in some cases the best way to promote a healthy microbial environment, either alone as support to the body’s own indigenous bacteria or as synbiotics, given alongside a probiotic. 

Prebiotics are food components, usually dietary fiber, that are not digestible. The benefits of dietary fiber are well-known, impacting such diverse areas as cardiovascular health, digestive health and weight. Most dietary fiber are complex polysaccharides.  However, this has expanded to include oligosaccharides, which are composed of fewer monosaccharides (simple sugars). Oligosaccharides make up most prebiotic fiber.[16]

Prebiotics persist intact through the digestive tract to the colon where they are fermented by bacteria and other microorganisms. Consumption of prebiotic foods or supplements can help ensure an optimal food source for colonic bacteria and production of the beneficial compounds (such as the SCFAs) resulting from the fermentation process.

Though prebiotics can fairly easily be obtained through the ingestion of certain foods (such as oats that contain beta glucan, and apples, which contain pectin), many of the best sources for prebiotic fiber are foods such as Konjac root and seaweed, that are not regular parts of the western diet.  Therefore, prebiotics are available in supplemental form.  Some prebiotics are also antioxidants and can provide additional benefits to the human host.   

The research on probiotics and prebiotics continues to expand as more and more information is uncovered about the positive functions that the human microbiome provides in supporting and maintaining human health. 

[1] https://www.prnewswire.com/news-releases/global-probiotics-market-to-202...

[2] https://www.healthline.com/health/probiotics-and-digestive-health#digest...

[3]Benef Microbes (2011) 2(2):93-101

[4] Int J Gen Med (2012) 5:991-997

[5] Exp Opin Biol Ther (2013) 13(3):339-43

[6] Drug Healthc Patient Saf (2014) 6:15-20

[7] Int J Gen Med (2015) 8:303-8

[8] Eur Rev Med Pharmacol Sci (2016) 20(21):4601-06

[9] Minerva Pediatrica (2018) 70(3):240-5

[10] Int J Gen Med (2019) 12:213-17

[11] J Med Microbiol (2013) 62:875-94

[12] Int J Pharma Bio Scie (2015) 6(1):242-50

[13] Clin Cosm Invest Dentistry (2015) 7:107-13

[14] Circulation (2019) 139(5):647-59

[15] Probiotics Antimicrob Proteins (2018) 10(1):1-10

[16] Nutrients (2013) 5(4):1417-35