Team:WLC-Milwaukee/Probiotics

Definition of probiotic

Bacteria are known to inhabit even the most extreme environments on earth. They are everywhere, and in large numbers. For every human cell of your body, there are approximately 10 microbial cells in or on you. Thankfully, relatively few are pathogenic. Many are merely opportunistic pathogens and some are harmless to us. Some are actually beneficial, participating in mutualistic relationships and composing what is known as the microflora. “The gut microflora is an essential component of the healthy human and is essential for optimal resistance to disease.”[1]

Coined in 1965, the word ‘probiotic’ literally means ‘for life.’ Thus it follows that anything that supports life, rather than inhibits it, could be considered a probiotic. This very broad definition is misleading if taken at face value. For instance, any pharmaceutical drug (that does not cause extreme side effects) could be a probiotic. What makes probiotics unique is the application of live microorganisms. While often applied to the digestive system, it is not limited to this application. Probiotics have been developed for the mouth, gastrointestinal tract, upper respiratory tract, and urogenital tract[2]. A more accurate definition of a probiotic is “a mono- or mixed culture of live microorganisms, which when applied to animal or man, affect beneficially the host by improving the properties of the indigenous microflora.”[2]

Regulations for probiotics

Probiotics must pass rigorous testing and documentation before becoming suitable for the market. It is necessary to clearly identify the genus, species, and strain of the bacteria used and a sample must be deposited in the international culture collection.[3] Safety tests are the first conducted; in vitro scenarios are performed followed by in vivo scenarios.[3]

Common in vitro tests include resistance to gastric acidity, bile acid resistance, adherence to mucus and/or human epithelial cells and cell lines, antimicrobial activity against potentially pathogenic bacteria, ability to reduce pathogen adhesion to surfaces, bile salt hydrolase activity, and resistance to spermicide depending on the purpose and location of implementation of the probiotic strain.[3] Strains selected for probiotic use should have a GRAS (Generally Regarded As Safe) status as well. Characterization for antibiotic resistance patterns, metabolic activities, side-effects, toxin production, and hemolytic activity should also be performed.[3] The mechanism of the probiotic should be determined.

In vivo tests on animals and humans are also necessary. Administration of the probiotic strain to immunocompromised animals to test against opportunistic pathogenicity is encouraged.[2] Probiotics must cause statistically significant biological improvements when compared to a placebo. These improvements may be evident in condition, symptoms, reduced risk of disease, longer remission times, or faster recovery from pathogens. Finally, repetition of trials is required for validation of effectiveness and potential side effects are monitored.

Selection of a probiotic strain is very important. Ideally the selected strain can be initially found in the target organism. For example, a probiotic strain for humans could originally be found in the gastrointestinal tract of a human. Furthermore the GRAS status is needed.[1] Lactic acid bacteria are frequently used for this reason. Probiotics intended for the gastrointestinal tract must be able to survive the acidic environment of the stomach. The presence of the probiotic must not elicit the host’s immune system to produce antibodies against it. However, some probiotics are used to increase the activity of the immune system.[1],[4] Other advantages characteristic of a probiotic strain may include adherence to the host’s cells, antibiogram profiles, production of antibacterial factors targeting pathogens, metabolic activity, technological suitability, anti-inflammatory properties, antimutagenic and anticarcinogenic properties, or site specific delivery of recombinant proteins.[1]

When the probiotic has passed sufficient testing and is ready for market, proper labeling must be observed. An appropriate label should contain the genus, species, strain, shelf-life, viable number of bacteria at the end of the shelf-life, effective dose, specific health claim(s), storage conditions, and corporate contact information.[3] The probiotic product can take many forms: freeze-dried powders, liquid suspensions, granules, paste, or gels.[2]

Difficulties arise for multiple reasons. It is common to have mixed cultures in probiotics. Unfortunately this makes it more difficult to isolate and test any one component or strain for probiotic effects and even more unlikely to determine the exact mechanism by which the probiotic functions. Additionally in vitro and in vivo tests are not always representative of the complex system of a living mammal.[4] It is very difficult to predict the effects of introducing a probiotic because there are variations between the microflora of any two individuals.[2] This is because both humans and livestock obtain their microflora after birth from exposure to the environment.[4],[5] It is a very complex dynamic composed of the mammal, bacteria, protozoa, fungi, archaea, and even viruses.[5] Finally, it may also be difficult to attain statistically significant results. If a probiotic vaguely claims to improve digestive health, it becomes very difficult to obtain quantitative data that verifies the claim.[3],[1] This in part has led to the public’s lack of confidence in probiotics. There must be scientific data to validate any probiotic claims.

Probiotics in use

An array of organisms has already been used as probiotics. As of 1992 probiotics have frequently utilized bacteria from the following genera: Lactobacillus, Bifidobacterium, Streptococcus, Lactococcus, Enterococcus, Leuconostoc, Propionibacterium, Pediococcus, Saccarharomyces, Escheriscia, and more.[1] Lactic acid bacteria are often favored for their GRAS status and pre-existing presence in the gut. One of the most visible uses of probiotics for consumers is the yogurt section of the grocery store. Some of the brands that claim probiotic status in some of their products are Dannon, Yoplait, Stonyfield Farms, and Chobani. These products typically claim to aid in digestive health with Lactobacillus bulgaricus, Streptococcus thermophiles, Lactobacillus acidophilus, Bifidobacterium bifidum, and Lactobacillus casei being the most common bacteria used.[6] Probiotics have also been used successfully in the treatment of upper respiratory infections and otitis by outcompeting pathogens.[7] The probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 suspended in skim milk as an oral intake has been clinically shown to treat bacterial vaginosis in women in as little as one week.[8] Work has also been done with some success on probiotics for oral health itself. “Probiotics may control dental caries in children due to their inhibitory action against cariogenic streptococci.[9]” The future seems bright for oral probiotics.

[9]

Probiotic use is not limited to humans but is common for livestock too. Most of these probiotics target the gastrointestinal tract and aim to increase feed efficiency and weight gain, limit ruminal acidosis, reduce the risks associated with weaning, reduce pathogen colonization, increase milk production and quality, improve meat quality, limit diarrhea, and to promote optimal microbiota for general health.[5] Ruminants, horses, pigs, poultry, and even fish and shrimp have benefited from probiotics.[5] Probiotics are an alternative to antibiotics, the use of which risk increasing bacterial resistance to the limited number of known antibiotics.

Probiotic Mechanisms

There are various mechanisms by which a given probiotic affects a benefit to its host. Livestock probiotics may encourage additional growth due to a better feed conversion, balance a disrupted microflora with healthy colonization, or pre-digest anti-nutritional factors for the host.[2] In humans probiotics may also be used to re-establish a healthy microflora, outcompete pathogenic bacteria for adherence to the intestinal epithelium, lower serum cholesterol, reduce mutagenicity and tumor formation, metabolize lactose, improve the absorption of calcium, or synthesize vitamins to name a few.[2] Some probiotics produce acid thereby lowering the gut pH which promotes the growth of the native microflora and suc