Update Definitions Of Probiotics, Prebiotics and Synbiotics
- Probiotics are microorganisms that provide health benefits when consumed, as claimed by some. The term probiotic is currently used to name ingested microorganisms associated with beneficial effects to humans and animals. Introduction of the concept is generally attributed to Nobel Prize recipient Eli Metchnikoff, who in 1907 suggested that “the dependence of the intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes”. A significant expansion of the potential market for probiotics has led to higher requirements for scientific substantiation of putative beneficial effects conferred by the microorganisms.
- Probiotics are microorganisms (bacteria, yeast) that exert a beneficial effect on host health. When some of these microorganisms are ingested, they are able to resist the physicochemical conditions prevailing in the digestive tract, and the strains most frequently used as probiotics belong to the genera Bifidobacterium and Lactobacillus. Allochthonous lactobacilli and bifidobacteria (probiotics) ingested as food or supplements need to be differentiated from the autochtonous organisms that constitute human commensal microbiota. The populations of these bacterial genera, whatever their origin (allochthonous or autochtonous), differ between individuals and can be affected by environmental factors such as drugs and diet. Probiotics can act on the gut immune system (as discussed later). They also play non-immune, protective roles by directly blocking intestinal pathogenic microbes and enhancing mucosal integrity via epithelial cell stimulation.
- The World Health Organization’s 2001 definition of probiotics is “live micro-organisms which, when administered in adequate amounts, confer a health beneﬁt on the host”. Following this definition, a working group convened by the FAO/WHO in May 2002 issued the “Guidelines for the Evaluation of Probiotics in Food”. This first global effort was further developed in 2010, two expert groups of academic scientists and industry representatives made recommendations for the evaluation and validation of probiotic health claim. The same principles emerged from those groups as the ones expressed in the Guidelines of FAO/WHO in 2002. This definition, although widely adopted, is not acceptable to the European Food Safety Authority because it embeds a health claim which is not measurable.
- A consensus definition of the term “probiotics”, based on the available information and scientific evidence, was adopted after a joint Food and Agricultural Organization of the United Nations and World Health Organization expert consultation. In October 2001, this expert consultation defined probiotics as: “live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host”. The FAO/WHO consultation was also a first effort towards the assessment of probiotics efficacy and resulted in May 2002 in a document named “Guidelines for the Evaluation of Probiotics in Food”. This effort is accompanied by local governmental and supra-governmental regulatory bodies requirements to better characterize health claims substantiations.
- A group of scientific experts assembled in London, UK, on October 23, 2013, to discuss the scope and appropriate use of the term ‘probiotic.’ The meeting was motivated by developments in the field since 2001. The panel’s conclusions were published in June, 2014 as an open access paper in Nature Reviews in Gastroenterology and Hepatology.
- Probiotics have to be alive when administered. One of the concerns throughout the scientific literature resides in the viability and reproducibility on a large scale of the observed results, as well as the viability and stability during use and storage and finally the ability to survive in the intestinal ecosystem. Probiotics must have undergone controlled evaluation to document health benefits in the target host. Only products containing live organisms shown in reproducible human studies to confer a health benefit can actually claim to be a probiotic. The correct definition of health benefit, backed with solid scientific evidence, is a strong element for the proper identification and assessment of the effect of a probiotic. This aspect represents a major challenge for scientific and industrial investigations because several difficulties arise, such as variability in the site for probiotic use (oral, vaginal, intestinal) and mode of application.
- The probiotic candidate must be a taxonomically defined microbe or combination of microbes (genus, species and strain level). It is commonly admitted that most effects of probiotic are strain-specific and cannot be extended to other probiotics of the same genus or species. This calls for a precise identification of the strain, i.e. genotypic and phenotypic characterization of the tested microorganism.
- Directly blocking intestinal pathogenic microbes Probiotics can directly inhibit the growth of pathogens by producing antibacterial substances, including bacteriocins (such as lantibiotics) and different acids (acetic, lactic, and propionic acid) [19, 20]. They can also decrease the adhesion of pathogens and their toxins to the gastrointestinal tract through their ability to adhere to intestinal epithelial cells. In vitro studies have demonstrated that probiotics possess lectin-like adhesion components able to bind on carbohydrates from glycoconjugate receptors of the epithelial cell surface, thus blocking pathogen binding to intestinal epithelial cells. Moreover, some probiotic strains belonging to the Lactobacillus genus have displayed in vitro abilities to bind to the surface of enterocytes.
- Enhancing mucosal integrity First, probiotic bacteria can enhance the integrity of the intestinal barrier. Indeed, Ewaschuck et al. established that Bifidobacterium infantis increases resistance in an in vitro model of the intestinal barrier (T84 human epithelial cells), and other probiotics, such as Lactobacillus plantarum, act on tight junctions by increasing the expression of zonula occludens proteins and occludins. Probiotics are also able to induce the production of cytoprotective substances by enterocytes, such as the heat shock proteins and antimicrobial peptides, e.g., defensin and mucin, to prevent bacterial adherence. Finally, they may be involved in preventing cytokine-induced epithelial damage by promoting the survival of intestinal epithelial cells by activating antiapoptotic and inhibiting proapoptotic pathways.
- Probiotics are able to exert an impact on the intestinal environment through different key non-immune mechanisms.
- Prebiotics is a general term to refer to chemicals that induce the growth and/or activity of commensal microorganisms (e.g., bacteria and fungi) that contribute to the well-being of their host. The most common example is in the gastrointestinal tract, where prebiotics can alter the distribution of organisms in the gut microbiome. However, in principle it is a more general term that can refer to other areas of the body as well. For example, certain hand moisturizers have been proposed to act as prebiotics to improve the activity and/or composition of the skin microflora.
- In diet, prebiotics are typically non-digestible fiber compounds that pass undigested through the upper part of the gastrointestinal tract and stimulate the growth and/or activity of advantageous bacteria that colonize the large bowel by acting as substrate for them. They were first identified and named by Marcel Roberfroid in 1995. As a functional food component, prebiotics, like probiotics, are conceptually intermediate between foods and drugs. Depending on the jurisdiction, they typically receive an intermediate level of regulatory scrutiny, in particular of the health claims made concerning them.
- Roberfroid offered a refined definition in the March 2007 Journal of Nutrition stating: A prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health.
- Additionally, in his 2007 revisit of prebiotics, Roberfroid stated that only two particular prebiotics then fully met this definition: trans-galactooligosaccharide and inulin. Other authorities also classify resistant starch, fructooligosaccharide (FOS) and lactulose as prebiotics. Mannan Oligosaccharides (MOS) have been termed as prebiotics but would more correctly be termed immunosaccharides.
- Researchers now also focus on the distinction between short-chain, long-chain, and full-spectrum prebiotics. “Short-chain” prebiotics, e.g. oligofructose, contain 2–8 links per saccharide molecule and are typically fermented more quickly in the right side of the colon providing nourishment to the bacteria in that area. Longer-chain prebiotics, e.g. inulin, contain 9-64 links per saccharide molecule, and tend to be fermented more slowly, nourishing bacteria predominantly in the left-side colon. Full-spectrum prebiotics provide the full range of molecular link-lengths from 2-64 links per molecule, and nourish bacteria throughout the colon, e.g. Oligofructose-Enriched Inulin (OEI). The majority of research done on prebiotics is based on full-spectrum prebiotics, typically using OEI as the research substanc
- A variety of molecules can be prebiotics, but the great majority is dietary fibers, such as oligosaccharides. Their principal effect is related to the metabolism of the microbiota. Indeed, if no dietary fiber is present in the colon, anaerobic bacteria draw their energy from protein fermentation. This metabolism leads to the production of toxic and potentially carcinogenic compounds (such as ammoniac or phenolic compounds). By contrast, the fermentation of carbohydrate (such as dietary fiber) generates SCFAs, such as acetate, propionate, or butyrate, which are not toxic to the host, and constitutes potential fuel for epithelial cells. For instance, in an in vivo rat model, a fructan (inulin, FOS)-enriched diet has increased the production of SCFA. The interesting properties of SCFAs on the intestinal barrier and gut immune system are discussed below. Several oligosaccharides are considered to be prebiotics, such as inulin, GOS, FOS, SOS, and xylooligosaccharides. The most widely studied have been inulin, GOS, FOS, and a mixture of GOS and inulin. These molecules are resistant to in vitro digestion by pancreatic and brush-border enzymes . Chicory is the principal industrial source of inulin, from which FOS are often obtained by partial enzymatic hydrolysis. GOS are produced from lactose using β-galactosidase. Each bacterial genus or species has a preferential substrate. Most strains belonging to the Bifidobacterium and Lactobacillus genera preferentially use fructans rather than glucose as a substrate. However, other bacteria such as Clostridia and Bacteroides are also able to grow on fructans. Nevertheless, their growth is less efficient than that of Bifidobacterium because of less-efficient substrate absorption (notably on oligofructose). Thus, prebiotics act first to ensure selective stimulation of the activity of beneficial autochtonous bacterial strains, but they do not stimulate the same genera of intestinal microbiota in humans and rodents. Indeed, in humans, prebiotics specifically increase bifidobacterial populations in fecal samples, whereas lactobacilli populations are increased significantly in the fecal microbiota of rodents (rat, mouse). Last but not least, some prebiotics (GOS) can exert a direct antimicrobial effect, as they can adhere to the binding sites of bacteria on the enterocyte surface and thus, block the adhesion of pathogenic bacteria to intestinal epithelial cells
- Although it is clear that prebiotics have some effects on microbiota (modification, stimulation, antipathogenic effect), little is known about the specific action of each type of oligosaccharide on the various genera and species that make up the microbiota.
- A combination of probiotic(s) and prebiotic(s) constitutes a synbiotic , which can stimulate and increase the survival of probiotic and autochthonous-specific strains in the intestinal tract. Su et al. administered some combinations to mice, each containing one prebiotic (FOS, SOS, or inulin) and one probiotic (Lactobacillus acidophilus, Bifidobacterium lactis, or Lactobacillus casei). They then analyzed the amounts and survival of each probiotic strain in fecal samples. A SOS- or FOS-containing diet appeared to stimulate the growth of L. acidophilus and sustain its highest level. FOS and inulin dietary treatment exerted the same effects on B. lactis. SOS, FOS, or inulin improved the survival and retention time of L. casei. Such effects have also been demonstrated in humans, as the administration of probiotic LGG with GOS was seen to significantly increase the amount of allochtonous Lactobacillus rhamnosus and autochthonous bifidobacteria and lactobacilli in feces from treated children.
- Synbiotics refer to nutritional supplements combining probiotics and prebiotics in a form of synergism, hence synbiotics. The synbiotic concept was first introduced as “mixtures of probiotics and prebiotics that beneficially affect the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract, by selectively stimulating the growth and/or by activating the metabolism of one or a limited number of health-promoting bacteria, thus improving host welfare”.
- Probiotics are live bacteria which are intended to colonize the large intestine and confer physiological health benefits to the host. A prebiotic is a food or dietary supplement product that confers a health benefit on the host associated with modulating the microbiota. Prebiotics are not drugs, not functioning because of absorption of the component, not due to the component acting directly on the host, and are due to changes to the resident bacteria – either changing the proportions of the resident bacteria or the activities thereof. Measurable changes to the microbiota in the absence of a desirable physiological consequence in the host does not qualify as a prebiotic. A prebiotic may be a fiber, but a fiber is not necessarily a prebiotic.
- Using prebiotics and probiotics in combination is often described as synbiotic, but the United Nations Food & Agriculture Organization (FAO) recommends that the term “synbiotic” be used only if the net health benefit is synergistic. Probiotic bacteria may colonise the upper part of the intestine to avoid the adhering of pathogens to the intestinal tract and may help in digestion. A prebiotic is a fiber such as fructose oligosaccharide, galactose oligosaccharide, etc., and is consumed that is intended to stimulate the microflora in the large intestine. The combination thus works separately in the small and large intestine, but synergistically as they increase the overall gut health. A common mistake is to require that the prebiotic be shown to increase the population and/or function of the probiotic it is paired with, as the probiotic is an external species, whereas prebiotics stimulate the flora which is already present.
- Human breast milk contains oligosaccharides (more diverse and more complex than those found in many animal milks) and lactic acid bacteria, which may be potential probiotics . Breast milk can therefore be considered as a synbiotic food. It has been evidenced that bacteria from human milk can colonize the gut of a breast-fed child. Some studies have also suggested that oligosaccharides from breast milk may influence the establishment of autochtonous microbiota in breast-fed children. Indeed, differences in terms of microbiota composition have been observed between breast-fed and formula-fed children. In particular, it has been established that the Bifidobacterium genus is more common in the feces of breast-fed infants
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