World Gastroenterology Organisation Global Guidelines: Probiotics and Prebiotics

Abstract

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 c