Probiotics

Did you know? Our ancestors took the ancestors of today’s probiotics!¹ From Neolithic times, fermentation of certain foods has been seen to hold incredible virtues. Milk, wheat, or vegetables became easier to preserve, tastier, easier to digest… and better for health.^1,2

From the beginnings of time, at least 5000 years ago, the Egyptians, Romans and Hindus already appreciated fermented milk,² and the Turks considered it to be the elixir of life. Is it the secret to their legendary strength? Three centuries before our era, Chinese workmen building the Great Wall of China ate fermented cabbage to keep healthy.² The famous Hippocrates, “father of medicine” recommended that Olympic athletes eat cheese.¹ Even the soldiers of the terrifying Genghis Khan found fermented milk to be a source of vigor that allowed him to win battles!³ But it was not until the beginning of the 20th century, particularly after Louis Pasteur’s work, that we discovered that these virtues were due to beneficial microorganisms.¹

What is a probiotic? 

Probiotics are “live microorganisms which when administered in adequate amounts confer a health benefit on the host”. ^4,5
Do you need explanations for this original expert version?

A probiotic is not… 

• … an antibiotic, quite the contrary! The term “probiotic” (for life) was suggested by researchers in the 1960s, as opposed to “antibiotic” (against life).¹
• … a microbiota, which describes all the microorganisms present in a given environment - such as the gut. The microbiome, is simply the genome (all the genes) of all these microorganisms!⁷
• … a prebiotic, consists of special, non-digestible food fibers that specifically nourish the good bacteria in the microbiota and, thereby, are beneficial for health.⁸ When they are added to probiotics in specific products, they are called symbiotics.⁹
• … a fermented food, which is a food that has been elaborated with certain living microorganisms and via certain enzymatic transformations—such as yogurt, cheese, fermented cabbage—is not necessarily a probiotic even though it has health benefits.¹⁰
• … fecal microbiota transplantation (FMT) is a treatment consisting of treating the microbiota of a sick person by transplanting that of a healthy donor. Currently, FMT is only used in cases of relapsing intestinal infections caused by a bacterium called “Clostridioides difficile”.¹¹

What are probiotic microorganisms? 

Commonly called “microbes” or even “germs”, microorganisms are “microscopic” living beings, that means that they cannot be seen by the naked eye.¹² They often consist of only one cell! 

Microorganisms include bacteria, which are ubiquitous in our environment: they can be found in the earth, water, and even on and in our bodies!^{12, 13} Microscopic fungi can also be found: yeasts (from Saccharomyces, the baker’s yeast, to Candida, which causes fungal infections) or molds (like Penicillium, which gives Roquefort cheese its “blue” color, but also penicillin, the famous antibiotic).^12,14,15,16 Viruses are also microorganisms, but as they cannot survive without infecting a cell, they are still not considered as “living beings”.^12,17 There are also amoeba, microalgae, etc.^18,19 This little world is actually gigantic: there is already a billion bacteria in a teaspoon of earth! But fear not! Over 99% of them are harmless for humans.^12,20

The microorganisms that are most commonly used as probiotics are:

• bacteria from the human microbiota or from fermented dairy products, lactobacilli (sidenote: Lactobacilli Rod-shaped bacteria whose main characteristic is the production of lactic acid, from where they get the name “lactic acid bacteria”.  Lactobacilli are present in the oral, vaginal and gut microbiota of humans, but also in plants and animals. They are found in fermented foods, such as dairy products (e.g. certain cheeses and yoghurts), pickles, sauerkraut, etc. Lactobacilli are also found in probiotics, with certain species recognized for their beneficial properties.   W. H. Holzapfel et B. J. Wood, The Genera of Lactic Acid Bacteria, 2, Springer-Verlag, 1st ed. 1995 (2012), 411 p. « The genus Lactobacillus par W. P. Hammes, R. F. Vogel Tannock GW. A special fondness for lactobacilli. Appl Environ Microbiol. 2004 Jun;70(6):3189-94. Smith TJ, Rigassio-Radler D, Denmark R, et al. Effect of Lactobacillus rhamnosus LGG® and Bifidobacterium animalis ssp. lactis BB-12® on health-related quality of life in college students affected by upper respiratory infections. Br J Nutr. 2013 Jun;109(11):1999-2007. ) (Lactobacillus) and bifidobacteria‎ (sidenote: Bifidobacterium A genus of Y-shaped bacteria, most species of which are beneficial to humans. They are found in the gut of humans, and in some yogurts.
  
  They:
  - Protect the gut barrier 
  - Participate in the development of the immune system and help fight inflammation 
  - Promote digestion and improve symptoms of gastrointestinal disorders Sung V, D'Amico F, Cabana MD, et al. Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis. Pediatrics. 2018 Jan;141(1):e20171811.  O'Callaghan A, van Sinderen D. Bifidobacteria and Their Role as Members of the Human Gut Microbiota. Front Microbiol. 2016 Jun 15;7:925. Ruiz L, Delgado S, Ruas-Madiedo P, et al. Bifidobacteria and Their Molecular Communication with the Immune System. Front Microbiol. 2017 Dec 4;8:2345. ) (Bifidobacterium); ^3,21
• yeasts, such as Saccharomyces boulardii, isolated from the skin of lychees.^3,15

Have you forgotten your Latin?

Think of a fruit salad with plums, cherries, peaches and nectarines. They all come from the same genus of tree, the Prunus. For example, the species Prunus avium gives cherries, while Prunus persica gives peaches - of which there are even more varieties: yellow, white, smooth or fuzzy, round or flat, etc.²²

How are probiotics chosen?

Finding the “chosen ones” among the billions of species of microorganisms: that is the hard task that researchers face! Probiotic species often bear the names of their researchers, to commend their efforts: Saccharomyces boulardii was isolated by Henri Boulard²³ and Lactobacillus reuterii (which is now called Limosilactobacillus reuteri²⁴) by Gerhard Reuter²⁵. 

Regardless of whether they come from milk, fruit, or the human body, potentially beneficial microorganism species are studied from every conceivable angle in order to find the most promising strains.

• The first stage consists in identifying them, following the characteristics of their genome. The microorganisms are classified. They are given a name and a strain number.^4,26 
• The second stage consists in gradually reducing the potential candidates on the basis of their beneficial properties, such as anti-pathogenic, anti-cholesterol, or bowel-regulating actions.^4,26 
• The third stage consists in verifying their safety, i.e., whether there are any health risks; researchers therefore check whether they contain antibiotic-resistant genes, toxins, and whether they cause any undesirable effects. They also check whether the candidate probiotics are capable of surviving in certain extreme conditions, such as the gut (temperature, pH, bile acids, etc.).^4,26
• The fourth stage is not to be taken light-heartedly. It is when the efficacy of the probiotic is validated in humans, in what are called “clinical trials”, which should follow precise recommendations from the local or national health care authorities. It is at this stage that the tested microorganism can be classified as a probiotic.^4,26
• In the last stage, researchers ensure that the probiotic is alive and remains at the effective dose throughout the product’s shelf-life. The probiotics are then stored in an “international microbial strain bank”.^4,26

What are probiotics for? 

Our bodies contain several microbiota. The most important one is in the gut (that is, the “intestinal flora”), but there is also a microbiota of the skin, the vagina, the mouth, the respiratory tract, etc.^28,29 Billions of microorganisms work together within these microbiota.^28,30 The majority is harmless or beneficial for health.³¹ Some are potentially pathogenic; in other words, they could cause diseases, but their development is impeded by “friendly” microorganisms³². For different reasons, such as unhealthy eating, stress, disease, or a course of antibiotics, the equilibrium of the microbiota can be disrupted. This is called “dysbiosis (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) ”.^28,30 The composition of the microbiota is changed; it becomes weaker, beneficial microorganisms are less abundant, and pathogens seize the opportunity to colonize the space and multiply…³³

By reinforcing the microbiota, probiotics can help it to maintain or regain its equilibrium, acting on our immune defense system by reducing inflammation, protecting us by attacking pathogens (sidenote: Pathogen A pathogen is a microorganism that causes, or may cause, disease. Pirofski LA, Casadevall A. Q and A: What is a pathogen? A question that begs the point. BMC Biol. 2012 Jan 31;10:6. ) or their toxins. They thus prevent or correct the disorders or diseases associated with dysbiosis.^34,35,34 Nonetheless, depending on the strain, probiotics have different modes of action, and a specific beneficial effect may not be extrapolated from one strain to another.³⁷

Why take probiotics? What are the benefits? What is in it for me?

Probiotics have several benefits for our health. However, according to the efficacy that each probiotic strain has shown in studies conducted on humans, they have proven their worth in very specific situations.^5,38

• Digestive system disorders, such as antibiotic-associated diarrhea,³⁹ C. difficile diarrhea,⁴⁰gastroenteritis,⁴¹ traveler’s diarrhea,⁴² functional bowel disorders (or “irritable bowel”),^43,44 lactose digestion disorders,²¹ inflammatory bowel diseases (IBDS)⁴⁵ etc
• Winter respiratory tract infections⁴⁶
• Skin conditions⁴⁷
• Urinary tract infections⁴⁸
• Vaginal infections⁴⁹

How are probiotics made?

Probiotics are manufactured using a delicate technical process with strict quality controls at every stage of the production line. In fact, they must be produced in a way that guarantees the end product meets all quality and safety standards. The probiotic micro-organisms must stay alive, in a sufficient number and stable until the end of the product’s shelf life, be in the correct dose to produce the stated benefits, and be free from contaminants.^5,6,51

This infographic is a simplified and non-exhaustive illustration of the process for selecting and manufacturing probiotics with theoretical examples of quality controls.

Stages of manufacture^6,52

This step-by-step process is a simplified and non-exhaustive illustration of the process for manufacturing probiotics.

At each stage of the manufacturing process - even sometimes at several points during a single stage - samples are taken and analyzed to ensure that the product is compliant, in other words to check for optimal quality and purity.⁶ The micro-organisms must still be alive and safe to consume.⁶ So that consumers can have complete faith in the quality of their products, some laboratories use not only internal checks but external independent assessors to ensure that the entire manufacturing and quality control process complies with regulations and best practice.²⁷

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Microbiota's world

The Biocodex Microbiota Institute is dedicated to education about human Microbiota for General Public and Healthcare Professionals, it doesn't give any medical advice.

We recommend you to consult a healthcare professional to answer your questions and demands

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