Probiotics: essential information for understanding and choosing them correctly.
What exactly are probiotics? They were not “officially” defined until the 21st century. However, consumption of these beneficial microorganisms goes back to time immemorial.
About this article
Table of contents
Table of contents
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?
On good form, ready to act: dead microorganisms are not probiotics!
Like bacteria or yeasts.
Just the right amount to act effectively and safely.
In this case, they have a positive effect on the health of the person taking them.6
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,
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.
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.
- 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
All are designated by a specific Latin name
- Their genus comes first, for example Lactobacillus,
- followed by the species within the genus, which gives for example Lactobacillus “acidophilus”,
- and finally, the strain contained within this species, in the form of a series of letters and/or numbers, which like a barcode indicates and precisely identifies the microorganism. The strain differentiates the genetic particulars of each species of microorganism, making each probiotic unique.21
For example, Lactobacillus acidophilus XYZ123
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 “ (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
Have you heard of "dysbiosis"?
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 (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 manufacture6,52
This step-by-step process is a simplified and non-exhaustive illustration of the process for manufacturing probiotics.
The chosen micro-organism is cultured with sterilized nutritional substances to encourage it to multiply.
This first culture is transferred into successive (sidenote: Fermenter Device or container in which micro-organisms multiply under controlled culture conditions. Mustafa MG, Khan MGM, Nguyen D, et al. (2018) Omics Technologies and Bio-engineering: Volume 2: Towards Improving Quality of Life, , pp. 233-249. ) (medium-sized, then getting bigger) for industrial-scale production. The growth conditions and absence of (sidenote: Contaminant Unwanted substance, impurity (e.g., pathogenic micro-organisms, residues, etc.) Motarjemi Y, Moy GG, & Todd EC (2014). Encyclopedia of food safety. ) must be closely monitored.
After they have multiplied, the micro-organisms are separated from the culture medium using centrifugation or filtration.
The resulting paste then undergoes fast freezing followed by dehydration to extract any water; this is known as lyophilization, which evaporates at least 96%53 of the remaining moisture. This preserves the micro-organisms whilst ensuring they stay alive.
The “dry cake” produced by the lyophilization process is crushed into a fine powder then mixed (depending on the manufacturer's production methods) with (sidenote: Excipient Substance added to an active ingredient to improve the appearance, taste, or preservation of a medicinal product, or to make it easier to formulate or administer. Cha J, Gilmor T, Lane P, Ranweiler JS. Ch.12 Stability Studies (2011) in Handbook of Modern Pharmaceutical Analysis. Separation Science and Technology, 10 (C), pp. 459-505. ) .
The powder is then packaged in its final form (hard capsules, sachets, ampoules, etc.). The choice and quality of formulation will increase the stability of the product. They are then packaged in their outer container or box.
The packaged probiotics are stored in controlled conditions (e.g., temperature, humidity, etc.).
The batches are then delivered to their point of sale, e.g., a pharmacy.
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
Choosing the right probiotic among so many is not always easy, as you can see. Not all probiotics are the same. And no probiotic strain or combination of strains will have all of the beneficial effects reported here at the same time.50 Ask your doctor or pharmacist for advice; they will recommend the right products based on your health condition.
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
1 Gasbarrini G, Bonvicini F, Gramenzi A. Probiotics History. J Clin Gastroenterol. 2016;50 Suppl 2, Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015:S116-S119.
5 Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514.
8 Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491-502.
9 Swanson KS, Gibson GR, Hutkins R, et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat Rev Gastroenterol Hepatol. 2020;17(11):687-701.
10 Marco ML, Sanders ME, Gänzle M, et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on fermented foods. Nat Rev Gastroenterol Hepatol. 2021;18(3):196-208.
11 Zallot, Camille : Transplantation de microbiote fécal et pathologies digestives, La Lettre de l'Hépato-gastroentérologue, Vol. XXI -n° 1, janvier-février 2018.
16 Ropars J, Caron T, Lo YC, et al. “La domestication des champignons Penicillium du fromage” [The domestication of Penicillium cheese fungi]. Comptes rendus biologies vol. 343,2 155-176. 9 Oct. 2020.
24 Zheng J, Wittouck S, Salvetti E, et al. A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol. 2020;70(4):2782-2858.
25 Britton RA. Lactobacillus reuteri. 2017 inThe Microbiota in Gastrointestinal Pathophysiology: Implications for Human Health, Prebiotics, Probiotics and Dysbiosis, 89–97. Edited by:MH. Floch, YRingel and WA Walker
40 McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease [published correction appears in JAMA 1994 Aug 17;272(7):518]. JAMA. 1994;271(24):1913-1918.
41 Guarino A, Ashkenazi S, Gendrel D, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014. J Pediatr Gastroenterol Nutr. 2014;59(1):132-152.
44 McKenzie YA, Thompson J, Gulia P, et al. (IBS Dietetic Guideline Review Group on behalf of Gastroenterology Specialist Group of the British Dietetic Association). British Dietetic Association systematic review of systematic reviews and evidence-based practice guidelines for the use of probiotics in the management of irritable bowel syndrome in adults (2016 update). J Hum Nutr Diet. 2016;29(5):576-592.
46 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;109(11):1999-2007.
48 Beerepoot MA, Geerlings SE, van Haarst EP, et al. Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review and meta-analysis of randomized controlled trials. J Urol. 2013;190(6):1981-1989.
53 Muller J, Ross R, Fitzgerald G, et al. Manufacture of Probiotic Bacteria. In: Charalampopoulos D., Rastall R.A. (eds) Prebiotics and Probiotics Science and Technology, 2009. Springer, New York, NY.