World Gastroenterology Organisation Global Guidelines: Probiotics and Prebiotics

The concept of beneficial microbes was first suggested by Elie Metchnikoff who postulated that lactic acid bacteria offered health benefits capable of promoting longevity. Disorders of the intestinal tract were frequently treated with viable nonpathogenic bacteria to change or replace the intestinal microbiota. The German professor Alfred Nissle isolated a nonpathogenic strain of Escherichia coli from the feces of a First World War soldier who did not develop enterocolitis during a severe outbreak of shigellosis. In Japan, Dr. Minoru Shirota isolated Lacticaseibacillus paracasei strain Shirota to battle diarrheal outbreaks. Today, a search of human clinical trials in PubMed shows that over 1500 trials have been published on probiotics. Although these studies are heterogeneous with regard to the strains and populations included, accumulated evidence supports the view that benefits are measurable across many different outcomes that have been assessed. This article is an update of a previous publication in the Journal of Clinical Gastroenterology,1 and is based on the guideline recently posted on the WGO website. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.2 Our glossary of terms is based on the definitions proposed by the International Scientific Association of Probiotics and Prebiotics. Lactobacilli, along with species of Bifidobacterium, have historically been common probiotics. In 2020, the genus Lactobacillus underwent a major restructuring to better address the wide diversity of microbes assigned to the genus. Twenty-three new genera were defined, including some with well-studied probiotic species (Table 1). TABLE 1 - New Names for Some Prominent Former Lactobacillus Probiotic Species. Still Included in the Lactobacillus Genus are Lactobacillus acidophilus, L. gasseri, L. crispatus, L. johnsonii, L. helveticus, and L. delbrueckii subsp. bulgaricus (Sometimes Abbreviated as L. bulgaricus). Former name New name Lactobacillus casei Lacticaseibacillus casei Lactobacillus paracasei Lacticaseibacillus paracasei Lactobacillus rhamnosus Lacticaseibacillus rhamnosus Lactobacillus plantarum Lactiplantibacillus plantarum Lactobacillus brevis Levilactobacillus brevis Lactobacillus salivarius Ligilactobacillus salivarius Lactobacillus fermentum Limosilactobacillus fermentum Lactobacillus reuteri Limosilactobacillus reuteri From the International Scientific Association for Probiotics and Prebiotics (ISAPP), “The big breakup of Lactobacillus,” available at https://www.nestlenutrition-institute.org/infographics/big-breakup-lactobacillus. GLOSSARY OF TERMS - Probiotics Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host Prebiotic A selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health Synbiotics A mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There are 2 types of synbiotic: complementary (mixtures of probiotics and prebiotics) and synergistic (mixtures of live microbes selected to utilize a coadministered substrate for a health effect) Postbiotic A preparation of inanimate microorganisms and/or their components that confers a health benefit on the host The yeast Saccharomyces boulardii and some E. coli and Bacillus species are also used. Newcomers to the probiotic ranks include Clostridium butyricum, recently approved as a novel food in the European Union. Lactic Acid Bacteria, which have been used for the preservation of food by fermentation for thousands of years, may also potentially impart health benefits. However, the term “probiotic” should be reserved for live microbes that have been shown in controlled human studies to impart a health benefit. Fermentation is globally applied in the preservation of a range of raw agricultural materials, such as cereals, roots, tubers, fruit and vegetables, milk, meat, and fish. The prebiotic concept, first proposed by Gibson and Roberfroid in 1995,3 is a more recent one than probiotics. The key aspects of a prebiotic are that it is nondigestible by the host and that it leads to health benefits for the consumer through a positive influence on the resident beneficial microbes. The administration or use of prebiotics or probiotics is intended to influence the gut environment, which is inhabited by trillions of microbes, for the benefit of human health. Both probiotics and prebiotics have been shown to have beneficial effects that extend beyond the gut, but this guideline will focus on gut effects. Prebiotics typically consist of nonstarch polysaccharides and oligosaccharides, although other substances are being studied as candidate prebiotics—such as resistant starch, conjugated linoleic acid, and polyphenols. Most prebiotics are used as food ingredients in foods such as biscuits, cereals, chocolate, spreads, and dairy products. Commonly known prebiotics are: Oligofructose (fructooligosaccharide, FOS) Inulin Galactooligosaccharides (GOSs) Lactulose Breast milk oligosaccharides (human milk oligosaccharides or HMOs) Lactulose is a synthetic disaccharide used as a drug for the treatment of constipation and hepatic encephalopathy. The prebiotic oligofructose is found naturally in many foods, such as wheat, onions, bananas, honey, garlic, and leeks. Oligofructose can also be isolated from chicory root or synthesized enzymatically from sucrose. Fermentation of oligofructose in the colon may result in several physiologic effects, including: Increasing the numbers of bifidobacteria in the colon Increasing calcium absorption Increasing fecal weight Shortening gastrointestinal transit time Lowering blood lipid levels However, the extent to which these physiological effects may be experienced by a consumer varies due to a number of factors, including baseline gut microbiota and diet. It has been hypothesized that the increase in colonic bifidobacteria benefits human health by producing compounds that inhibit potential pathogens, by reducing blood ammonia levels, and by producing vitamins and digestive enzymes. Synbiotics were originally described as appropriate combinations of prebiotics and probiotics. More recently, the concept of synbiotics has evolved to include both complementary and synergistic synbiotics. A complementary synbiotic is defined simply as a mixture of probiotic(s) and prebiotic(s), where the 2 components meet the criteria defined for each, including proper characterization, and are used at a dose shown to provide a health benefit. However, a synergistic synbiotic has been described as a mixture of a live microbe selected to utilize a coadministered substrate, which together leads to a documented health benefit. The components of a synergistic synbiotic do not need to independently meet the criteria for a probiotic or prebiotic (Fig. 1).FIGURE 1: Composition of complementary and synergistic synbiotics. A complementary synbiotic combines a prebiotic and a probiotic, which work independently to elicit one or more health benefits. The prebiotic functions by modulating the resident microbiota to elicit a health benefit. The synergistic synbiotic is composed of a substrate that is utilized by the coadministered live microorganism, enhancing its functionality. Components of synergistic synbiotics work together (not independently) to bring about the resulting health benefits. (Reproduced from Swanson et al4 CC BY 4.0).Genera, Species, and Strains Used as Probiotics A probiotic strain is identified by the genus, species, subspecies (if applicable), and an alphanumeric designation that identifies a specific strain (Table 2). In the scientific community, there is an agreed nomenclature for genus, species, and subspecies names. Strain designations, product names, and trade names are not controlled by the scientific community. According to the guidelines of the World Health Organization (WHO) and Food and Agriculture Organization (FAO; http://www.fao.org/3/a-a0512e.pdf), probiotic manufacturers should deposit their strains in an internationally recognized culture collection. Such will an designation to shows a of strains and the names with TABLE 2 - Used for Probiotic Genus Strain designation International strain designation Strain name Lacticaseibacillus rhamnosus The product name shown in the may be used in some of Food and TABLE - of Probiotic and Prebiotic The and the can be by or in the Probiotics or Prebiotics Probiotics benefits to increase to and increase A both and to food benefits food and for with to an for to inhibit intestinal for with Prebiotics of absorption of host Strain for probiotics are the to probiotic evidence is to benefits as the specific gastrointestinal in this to specific strains or strain combinations of probiotics at the of in a clinical should specific strains to the benefits based on human Some strains will have that may for and However, an concept in the of probiotics is to that some of probiotic activity are different species, or probiotics may in a with regard to their to intestinal or microbiota. the to acid or in the colon may be a benefit by many different probiotic some probiotic benefits may be by different strains of well-studied species of probiotic It is common in the of probiotics for and to include Such an is of the different strains are to be for the benefit being assessed. such should focus on The functions of both probiotics and prebiotics for gastrointestinal are with the microbes that in the human Prebiotics are utilized by beneficial of the community, promoting health. probiotics and host or probiotics and resident microbes a key for the health. The a number of microbes, in the colon and comprising of that over are in the colon of an human being a of than and are also with a in terms of may bacteria microbes an of to human the of species and the diversity is or of by the host by at through and by In the fecal composition is over In the human gut the 2 and and for more than of microbes. The are and The gut bacteria and their host is a influence of intestinal bacteria on is suggested by the of a number of in the of the and The over is for the and of and for the of In the microorganisms by available from or and to host studies have shown that populations of microbes and with or However, are not to the composition of human microbiota. bacteria as Bifidobacterium, and to be more with but it is a of to with these bacteria will health or of of Probiotics and Prebiotics Prebiotics intestinal bacteria by enhancing the numbers or of beneficial This may result in the of potentially microorganisms or reducing potentially of host microbiota. Prebiotics may also Probiotic strains may health effects through one or more of several identified Probiotics may the intestinal by by with or potential microbes, by such as and by with host through (Fig. can to of potential pathogens, an intestinal environment, the intestinal of and of the to are to the beneficial effects, including of the and of which is one of the recognized of of microbiota and probiotic with the host. The microbiota and probiotics with the host in and and of and (Reproduced with from through the have been in many of the A range of product food through available (Table TABLE - of Probiotics of Food or health with for the consumer or health health or with or health or drug to or drug to or or and the bacteria in is specific to The that can be on these types of on in the Most probiotics and prebiotics are as foods or products. of or is to be and are at the health a specific in where the and the of the product for use in is From a scientific of a probiotic product as on the should species with nomenclature with recognized names Strain designation of strain at the of The which should be based on of the physiological of the physiological as by for and The for probiotics was at in to a It is that the probiotic will at an of to by through the of foods, and on the is a Most from is based on strains than product names, which can on the It can be to probiotic strains to specific and not are to this has been in and the by from and to available evidence and The of probiotic on the are not to may not to The that are to probiotic include of of typically by through the of that of and nomenclature used to the genus, species, and and a strain designation for strain in the The dose for probiotics varies on the strain and Although many in the range of some have been shown to be at levels, some subsp. was in the of at the dose of other probiotic is to It is not to a dose that is for the should be based on human studies a health benefit. probiotics are are to during product typically in that at the of the it not the on the manufacturers will the dose at the (not at the time of probiotic strains have the of to during However, evidence of the of that for probiotics. 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Lactobacillus rhamnosus 2 and treatment Lactobacillus reuteri and L. reuteri 1 of 2 and treatment Saccharomyces boulardii or 2 in effects and Bacillus 2 2 in effects and of with strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. on for Lactobacillus 2 on for Lactobacillus and on for Lactobacillus subsp. on for of with and Lactobacillus in with Bacillus was more than in reducing strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. of of in Lactulose 1 of hepatic and from hepatic strains of L. L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. of hepatic strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. hepatic with Lactobacillus L. acidophilus, bifidobacteria and L. casei hepatic Lactobacillus hepatic Lactobacillus plantarum a of hepatic Lactobacillus bulgaricus and with L. and in Lactobacillus L. L. acidophilus, and L. 2 in along with and of in and activity Lactobacillus paracasei L. plantarum L. and L. delbrueckii subsp. bulgaricus and in and activity with subsp. and in in and 1 2 in and also Lactobacillus plantarum 1 2 in of and Escherichia coli on of Lactobacillus rhamnosus L. plantarum L. and in in and Lactobacillus subsp. L. L. delbrueckii subsp. bulgaricus on of Saccharomyces boulardii 2 in 1 2 in of in fermented milk and Lactobacillus in in Lactobacillus 2 on of Lactobacillus rhamnosus L. rhamnosus 2 in of on of Galactooligosaccharides 2 on of Lactobacillus plantarum L. plantarum or in strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. of 1 of and of in Bacillus 2 in and in Lactobacillus and L. reuteri on of in Lactobacillus rhamnosus L. plantarum and subsp. on of in Saccharomyces of in and Bacillus Lactobacillus L. delbrueckii bulgaricus L. casei L. plantarum L. rhamnosus L. L. salivarius and 2 of in with Lactobacillus 1 of 1 of Lactobacillus and L. subsp. of and Lactobacillus casei L. plantarum subsp. of in on the of in on the constipation Lactobacillus L. rhamnosus and of and in Lactobacillus reuteri 1 2 of and Lactulose 1 Prebiotics are used as Oligofructose 1 of by and Lactobacillus paracasei L. rhamnosus L. and in and strains Lactobacillus acidophilus, and 1 of colonic transit and in with constipation subsp. subsp. 1 or 1 in in with than Lactulose Bacillus 2 to the time to constipation as to Lactobacillus L. casei L. and with and colonic transit time in with constipation Lactobacillus casei strain Shirota in fermented milk of or in the Lactobacillus casei subsp. 2 in in Lactobacillus paracasei in in Lactobacillus salivarius L. The probiotic in with the and more than treatment Lactobacillus reuteri 1 and with and in of Lactobacillus plantarum L. and dose of of Lactobacillus L. rhamnosus L. paracasei and of due to Lactobacillus casei strain Shirota in fermented milk the of Lactobacillus in fermented milk of the of the of strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. bacteria 2 of strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. bacteria 2 of clinical in strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. bacteria 2 of in Clostridium of in strains of Lactobacillus L. L. acidophilus, L. delbrueckii subsp. and salivarius subsp. bacteria of Escherichia coli Nissle viable bacteria 2 2 of viable Lactobacillus acidophilus, and 2 in the clinical to with with live of Lactobacillus delbrueckii subsp. bulgaricus and of strain of product 1 Lactobacillus 1 and Lactobacillus rhamnosus 1 Lactobacillus plantarum L. plantarum of of with with of TABLE - of Probiotics and/or Prebiotics in Probiotic strain dose Probiotics as a 1 the of the of on an including in L. rhamnosus for 1 of of and for 1 of L. reuteri 1 to for 1 of L. rhamnosus L. reuteri 2 for for 1 of for of L. paracasei and for of L. rhamnosus strains or for of but not of of L. delbrueckii L. acidophilus, for of L. rhamnosus and L. a for the of of and of Probiotics as a 1 of for the of treatment 1 of and L. rhamnosus for the of treatment 1 of and probiotic Lactobacillus Lactobacillus Lacticaseibacillus paracasei plantarum Lacticaseibacillus rhamnosus and Ligilactobacillus salivarius for the of treatment and for of but not The of L. rhamnosus and 2 for the of treatment of of 1 and of of L. rhamnosus for the of the 1 of of enterocolitis and of 1 Some specific strains of probiotic may be for L. rhamnosus From 1 to 1 and and to 1 and subsp. or L. reuteri or 1 1 this strain is by but not or subsp. L. with milk subsp. L. rhamnosus and Probiotics as a 1 and/or effects of treatment 1 it was the of and in reducing gastrointestinal effects with Lactobacillus plantarum subsp. and boulardii L. plantarum L. and boulardii for and effects milk L. casei for Probiotics as a 1 L. reuteri for at 1 and/or time in but its in is for 2 and/or time in with L. rhamnosus and L. reuteri in a dose of of of for and/or time in L. paracasei L. plantarum L. L. delbrueckii subsp. bulgaricus and and for in L. reuteri to for 1 time in both and 1 evidence for the use of probiotics a in with L. reuteri to 2 1 L. rhamnosus to 1 Probiotics as a 1 clinical in with A mixture of strains paracasei L. plantarum L. L. delbrueckii subsp. bulgaricus and as or in to 1 2 and of Escherichia coli Nissle or in to and is available for and of A mixture of strains paracasei L. plantarum L. L. delbrueckii subsp. bulgaricus and 1 2 in with and Lactobacillus in with other strains of or Lactobacillus may be beneficial for levels of and lipid and in with However, evidence not of the beneficial strain of probiotic 1 studies with the strain boulardii European and European for and not controlled and probiotics to be described by genus, species, and strain in studies the benefit. the strain was not the strain designation was not positive studies studies results for its were studies were not studies in which the results for the were not a of the probiotic strains or prebiotics found to have a beneficial is clinical evidence to a specific probiotic strain and/or prebiotic is should be the of the of the The of in the trials was not assessed. The may not be as the publication of new studies is other probiotics and/or prebiotics in controlled trials may be The of evidence may the different shown are used in the The of the is There is evidence from studies to the in terms of The do not provide of but levels of evidence to