Probiotics are living microbes that are either the same as or similar to the microorganisms found naturally in the human body. They are known as “good bacteria” or “helpful bacteria,” and may be beneficial to health. The World Health Organization (WHO) defined probiotics in 2001 as live microorganisms that “when administered in adequate amounts, confer a health benefit on the host.” The English word pro-biotic is a compound of a Latin and a Greek word; it means “favorable to life.” It was introduced in an article published in Science in 1965 by Daniel Lilly and Rosalie Stillwell, two professors of biology at St. John's University in New York.
Prebiotics are substrates, mostly nondigestible types of plant fiber that stimulate the growth and activity of potentially beneficial bacteria and fungi in the digestive tract. Prebiotics were defined by Marcel Roberfroid, the first researcher to identify them, as “selectively fermented ingredients that allow specific changes, both in the composition and/or activity in the gastrointestinal microflora that confer benefits upon host well-being and health.”
Products that combine probiotics and prebiotics are known as synbiotics. Synbiotics are less well defined than either probiotics or prebiotics as of 2018. Synbiotic products may be either complementary, in which the probiotic and the prebiotic are chosen independently to benefit the host; or synergistic, in which a specific prebiotic is selected to support the growth of the chosen probiotic. Fermented dairy products such as yogurt and kefir are sometimes considered synbiotics when they are paired with honey or acacia gum. Other food combinations considered synbiotic include beans and sour pickles; yogurt and oats; feta cheese and onions; and kombucha with acacia gum.
The notion of improving health by supplementing the natural microflora of the human intestines with additional bacteria taken by mouth, however, arose only in the late nineteenth century. In 1907, the Nobel laureate Élie Metchnikoff (1845–1916) proposed in The Prolongation of Life: Optimistic Studies that ingesting lactic-acid–producing bacteria could lengthen the human lifespan. He drew this conclusion from the longevity of Bulgarian peasants whose diet included large quantities of yogurt. Metchnikoff himself began to drink sour milk on a daily basis and is known as the “father of probiotics.”
Metchnikoff attributed sickness and aging to a buildup of waste products in the colon (the lower part of the large intestine) and toxic materials leaking from the colon into the bloodstream (now referred to as gut permeability or leaky gut syndrome). He called the poisoning that resulted from this process autointoxication. Metchnikoff's autointoxication theory assumed that dietary changes that reduce toxic decomposition in the colon would be beneficial to health. Some observers knew about the use of lactic-acid bacteria in sausage-making to ferment the meat and protect it from spoilage. Because these bacteria are harmless to humans, it was thought that adding them to the diet by eating fermented foods would reduce the amount of toxins produced in the colon. The lactobacilli genus of bacteria, some of which are found in yogurt, was the first identified probiotic. In the 1920s and 1930s, many doctors recommended acidophilus milk, which contains the bacterium Lactobacillus acidophilus, for the treatment of constipation and diarrhea. This treatment was effective for many patients.
The next phase in the development of probiotics came in the 1950s, when medical researchers began to study L. acidophilus as a possible answer to some of the digestive side effects of antibiotics. It was known that antibiotic medications upset the natural balance of the intestinal microflora by killing off the beneficial as well as the disease-causing bacteria. Researchers thought that taking oral preparations of L. acidophilus might offset the side effects of antibiotics.
One of the chief difficulties in benefiting from probiotic supplementation, however, has been assuring survivability of the probiotic organisms. They must first pass through the highly acidic stomach and the digestive processes of the small intestine before colonizing the colon. In 1983, a new probiotic with exceptional survivability and colonization characteristics was isolated from the intestines of a healthy human and patented in 1985. This probiotic, screened from many strains of lactobacilli and named after its codiscoverers, Sherwood Gorbach and Barry Goldin, is known as lactobacillus GG or LGG. It was later reclassified as L. rhamnosus GG. It has been found to be effective against pseudomembranous colitis, an infection of the colon by Clostridium difficile as a result of antibiotic overkill of beneficial bacteria. The evidence for LGG's effectiveness in treating other forms of antibiotic-associated diarrhea, however, is only moderate.
Prebiotics were not defined until the mid-1990s. Glenn Gibson and Marcel Roberfroid coined the word prebiotic, defining it in a 1995 Journal of Nutrition article as a “non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health.” This definition was revised and expanded by the International Scientific Association for Probiotics and Prebiotics (ISAPP) in 2017 to include noncarbohydrate substances.
Probiotics, prebiotics, and synbiotics have become increasingly popular in the developed countries as of 2018. In 2012, the National Health Interview Survey (NHIS) in the United States reported that about 4 million adults (1.6% of the population) had used a probiotic or prebiotic within the previous month and that probiotics and prebiotics were the third most commonly used dietary supplements after vitamins and minerals. Global consumption of prebiotics and probiotics quadrupled between 2007 and 2015; and as of 2018, probiotics and prebiotics were the fastest-growing segment of the dietary supplement market worldwide, with sales of $522.2 million (in U.S. dollars) in 2015 and expected to reach $543.4 million by 2022.
Probiotics are live microorganisms that are taken internally to confer health benefits, usually said to include strengthening the immune system or treating dysbiosis (imbalance or maladaptation of microbes on the skin or inside the body) or other disorders of the digestive tract. Most probiotic microorganisms are nonpathogenic bacteria, and some are yeasts. They may be consumed in the form of functional foods, dietary supplements, or pharmaceuticals.
As of 2018, the United States had no legal definition of probiotics. Given the increased interest in these products since the early 2000s and disagreement as to which microbial species should be considered probiotics, the International Scientific Association for Probiotics and Prebiotics (ISAPP) issued a consensus statement in 2014 that serves as a widely accepted guideline. To be considered a probiotic, a bacterial or yeast species must be:
Prebiotics are sometimes referred to as fermentable fiber. They benefit the host by stimulating the growth of helpful bacteria and fungi. Prebiotics ferment in the colon, releasing short-chain fatty acids that increase the absorption of minerals in the colon. They also speed the passage of waste products through the digestive tract. The prebiotics studied most are fructooligosaccharides (FOS) and inulin (a form of FOS). These fructans are thought to be the most effective prebiotics. In addition to FOS, also rated as effective due to research findings are prebiotics classified as galactooligosaccharides (GOS). Prebiotics occur naturally in such foods as Jerusalem artichokes, bananas, dandelion greens, leeks, gar lic, chicory, wheat bran, and onions. In addition, prebiotic compounds, usually extracted from chicory root, are added to foods, drinks, cereals, cookies, breads, and baby formula.
As originally defined, a prebiotic is a food or food ingredient scientifically demonstrated to meet three criteria: 1) it must resist stomach acid and absorption in the upper digestive tract; 2) it must undergo fermentation by intestinal microflora; and 3) it must selectively stimulate the growth and reproduction of bacteria in the gut associated with health and well-being. In 2017, the ISAPP expanded the definition of prebiotic to include noncarbohydrates, substances other than food, and applications to body sites other than the digestive tract. The new definition of prebiotic is “a substrate that is selectively utilized by host microorganisms conferring a health benefit.” ISAPP maintains that the new definition will allow substances that stimulate the growth of bacteria other than bifidobacteria and lactobacilli to be considered prebiotics.
According to the National Center for Complementary and Integrative Health (NCCIH), probiotics might be useful in humans for the following purposes:
Prebiotics are used for the following purposes as of 2018:
It is thought that administration of prebiotics may also benefit humans by providing some protection against colon cancer and by enabling weight loss through promoting a feeling of fullness (satiety); however, as of 2018 data on the health effects of prebiotics were not as extensive as the data for the health effects of dietary fiber.
Regulatory issues regarding probiotics and prebiotics are complex in both Europe and the United States. In Europe, the European Food Safety Authority (EFSA) does not permit individual ingredients to be labeled as prebiotics but only as dietary fiber, and these products are not permitted to make any claims of health benefits. The EFSA also does not allow health claims to be made for probiotics, on the grounds that a cause-and-effect relationship between the microorganisms and their purported benefits has not yet been proven.
In the United States, probiotics and prebiotics may be regulated as food ingredients, as dietary supplements, or as drugs. Items marketed as dietary supplements may make statements about their effects on bodily structures or functions (such as “dietary supplement for management of diarrhea”), but they cannot make health claims (such as that the product lowers the risk of cancer) without FDA approval. The Federal Trade Commission (FTC) and the FDA have levied fines and issued warning letters to companies making exaggerated claims about the health benefits of probiotic products. Probiotics marketed as drugs must meet much more stringent requirements; they must be proven safe as well as effective through clinical trials and receive formal approval from the FDA before they can be sold.
Because government has established no overall framework for regulating probiotics and prebiotics, consumers should be careful to purchase only from reputable manufacturers. The NCCIH has noted that some probiotics contain fewer microorganisms than stated on the label, and others contain strains of bacteria other than those listed on the label. In addition, although manufacturers are supposed to state the number of bacteria or colony-forming units available at the end of the product's shelf life, many state the number present at the end of the manufacturing process, usually a much higher number.
Probiotics and prebiotics appear to be safe for most healthy adults; however, anyone considering using a probiotic dietary supplement should consult a physician first. Probiotics should not be given to children without a doctor's recommendation, and pregnant or nursing women should also consult their doctors before taking probiotics. The Academy of Nutrition and Dietetics recommends that people with disorders of the digestive tract or weakened immune systems should see a registered dietitian for specific advice before they take a probiotic or prebiotic.
Although serious side effects from probiotics are rare, some groups of people are at increased risk of adverse effects:
Some otherwise healthy adults experience bloating or flatulence (intestinal gas) while taking probiotics. These mild side effects usually resolve when the dosage is decreased or the probiotic is taken only every other day.
Severe adverse effects include the passage of live bacteria from the probiotic into the bloodstream (bacteremia) through the walls of a weakened digestive tract. Other adverse effects include interactions between probiotics and antibiotic or immunosuppressive drugs.
Present research in this field is moving in a number of different directions:
See also Asian diet ; Calcium ; Cancer ; Carbohydrates ; Constipation ; Crohn's disease ; Diarrhea diet ; Dietary supplements ; Fiber ; Inflammatory bowel disease ; Irritable bowel syndrome ; Magnesium ; Minerals ; Obesity ; Sugar ; Vitamins ; Whole grains .
Britton, Robert A., and Patrice D. Cani, editors. Bugs as Drugs: Therapeutic Microbes for the Prevention and Treatment of Disease. Washington, DC: ASM, 2018.
Floch, Martin H., editor. The Microbiota in Gastrointestinal Pathophysiology: Implications for Human Health, Prebiotics, Probiotics, and Dysbiosis. Boston: Elsevier, 2017.
Gupta, Vijai K., Helen Treichel, Volha Shapaval, et al., editors. Microbial Functional Foods and Nutraceuticals. Hoboken, NJ: John Wiley and Sons, 2018.
Watson, Ronald Ross, and Victor R. Preedy, editors. Probiotics, Prebiotics, and Synbiotics: Bioactive Foods in Health Promotion. Boston: Elsevier, 2016.
Barko, P. C., M. A. McMichael, K. S. Swanson, et al. “The Gastrointestinal Microbiome: A Review.” Journal of Veterinary Internal Medicine 32, no. 1 (January 2018): 9–25.
Bober, Josef R., Chase L. Beisel, and Nikhil U. Nair. “Synthetic Biology Approaches to Engineer Probiotics and Members of the Human Microbiota for Biomedical Applications.” Annual Review of Biomedical Engineering 20, no. 1 (May 22, 2018). [e-pub ahead of print] http://dx.doi.org/10.1146/annurev-bioeng-062117-121019 (accessed May 22, 2018).
Clemente, J. C., J. Manasson, and J. U. Schur. “The Role of the Gut Microbiome in Systemic Inflammatory Disease.” BMJ 360 (January 8, 2018): j5145.
Eom, Taekil, Yong Sung Kim, Chang Hwan Choi, et al. “Current Understanding of Microbiota- and Dietary Therapies for Treating Inflammatory Bowel Disease.” Journal of Microbiology 56, no. 3 (March 2018): 189–98.
Floch, M. H. “The Role of Prebiotics and Probiotics in Gastrointestinal Disease.” Gastroenterology Clinics of North America 47 (March 2018): 179–91.
Gibson, Glenn R., Robert Hutkins, Mary Ellen Sanders, et al. “Expert Consensus Document: The International Scientific Association for Probiotics and Prebiotics Consensus Statement on the Definition and Scope of Prebiotics.” Nature Reviews: Gastroenterology and Hepatology 14, no. 8 (August 2017): 491–502.
Hill, Colin, Francisco Guarner, Gregor Reid, 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.” Nature Reviews: Gastroenterology and Hepatology 11, no. 8 (August 2014): 506–14.
Hojsak, Iva, Valentina Fabiano, Tudor Lucian Pop, et al. “European Guidance on Paediatric Use of Probiotics States That Benefits Are Limited to Several Conditions and Urges Caution with Specific Vulnerable Groups.” Acta Paediatrica 107, no. 6 (June 2018): 927–37.
Hopkins, R. J., and R. B. Wilson. “Treatment of Recurrent Clostridium difficile Colitis: A Narrative Review.” Gastroenterology Report 6 (February 2018): 21–28.
Hutkins, Robert W., Janina A. Krumbeck, Laure B. Bindels, et al. “Prebiotics: Why Definitions Matter.” Current Opinion in Biotechnology 37 (February 2016): 1–7.
Krumbeck, J. A., J. Walter, and R. W. Hutkins. “Synbiotics for Improved Human Health: Recent Developments, Challenges, and Opportunities.” Annual Review of Food Science and Technology 9 (March 25, 2018): 451–79.
Szajewska, H., and M. Kolodziej. “Systematic Review with Meta-analysis: Lactobacillus rhamnosus GG in the Prevention of Antibiotic-associated Diarrhoea in Children and Adults.” Alimentary Pharmacology and Therapeutics 42 (November 2015): 1149–57.
American College of Gastroenterology (ACG). “Probiotics for the Treatment of Adult Gastrointestinal Disorders.” Patients.GI.org . http://patients.gi.org/topics/probiotics-for-the-treatment-of-adult-gastrointestinal-disorders (accessed May 22, 2018).
Institute of Food Technologists. “Prebiotics.” IFT.org . http://www.ift.org/Knowledge-Center/Focus-Areas/Food-Health-and-Nutrition/Prebiotics.aspx (accessed May 22, 2018).
National Center for Complementary and Integrative Health (NCCIH). “Probiotics: In Depth.” National Institutes of Health. https://nccih.nih.gov/health/probiotics/introduction.htm (accessed May 22, 2018).
U. S. Food and Drug Administration (FDA). “Complementary and Alternative Medicine Products and their Regulation by the Food and Drug Administration.” U.S. Department of Health and Human Services. https://www.fda.gov/regulatoryinformation/guidances/ucm144657.htm (accessed May 22, 2018).
Wolfram, Taylor. “Prebiotics and Probiotics: Creating a Healthier You.” Academy of Nutrition and Dietetics. https://www.eatright.org/food/vitamins-andsupplements/nutrient-rich-foods/prebiotics-andprobiotics-creating-a-healthier-you (accessed May 22, 2018).
Academy of Nutrition and Dietetics, 120 S. Riverside Plaza, Ste. 2190, Chicago, IL, 60606-6995, (312) 899-0040, (800) 877-1600, email@example.com, http://www.eatright.org .
American College of Gastroenterology (ACG), 6400 Goldsboro Rd., Ste. 200, Bethesda, MD, 20817, (301) 263-9000, firstname.lastname@example.org, http://www.acg.gi.org .
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International Scientific Association of Probiotics and Prebiotics (ISAPP), 230 Arena Boulevard, #245-172, Sacramento, CA, 95834, firstname.lastname@example.org, https://isappscience.org .
National Center for Complementary and Integrative Health (NCCIH), 9000 Rockville Pike, NIH Campus, Bldg. 31, Bethesda, MD, 20892, (888) 644-3615, https://nccih.nih.gov/tools/emailnccih , https://nccih.nih.gov .
Rebecca J. Frey, PhD