Category: Moms

Prebiotics and reduced risk of disease

Prebiotics and reduced risk of disease

Probiotics during pregnancy and breastfeeding might confer Prebiotics and reduced risk of disease protection against atopic wnd in the infant. Food Res. Only one study assessed the risk of food allergy and found a reduced risk RR: 0.

Prebiotics and reduced risk of disease -

The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic.

The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term 'prebiotic' by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category.

To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation. Improving human health through modulation of the microbiome is an evolving strategy that is part of a comprehensive, holistic approach to lifestyle wellness 1.

The rich, diverse microbial ecosystems inhabiting mucosal and cutaneous surfaces provide targets for approaches to maintain or improve health or to treat disease. The ability to shift the composition and metabolic signatures of these microbial populations is now possible, via dietary or non-dietary interventions 2 , 3.

Over 20 years ago, a class of compounds, termed prebiotics, were recognized for their ability to manipulate host microbiota to the benefit of the host 4. FOS and GOS currently dominate the prebiotic category as evidenced by numerous studies on their prebiotic effects.

Today, the prebiotic concept has expanded, in part, because of advances in tools for microbiome research for example, high-throughput sequencing , which have improved our knowledge of the composition of the microbiota and enabled identification of additional substances influencing colonization.

Concurrent with this progress is the realization that a broader range of beneficial microorganisms are affected by prebiotics and also that they might be effective at extraintestinal sites directly or indirectly 5. Furthermore, the use of prebiotics has expanded to production and companion animals 6 , 7 and categories beyond food.

Accordingly, researchers have advocated for reconsideration of the contemporary nature of prebiotics, which formed the aim of the consensus panel that was convened on 9 December in London, UK.

The various aspects looked at in this review of evidence were: evolution of the term prebiotic; effects and selectivity; substrates that are prebiotics; metabolism of prebiotics; host benefits; companion animals; and guidance for producers, consumers and regulators.

Herein, the term 'microbiota' refers to the collection of microorganisms in an ecosystem and 'microbiome' when genetic elements are also considered. A panel of experts was organized by the board of directors of the International Scientific Association for Probiotics and Prebiotics ISAPP , a non-profit collaboration of scientists dedicated to advancing scientific excellence in probiotics and prebiotics.

ISAPP activities are determined by the board of directors, comprising global academic scientists. Through its Industry Advisory Committee, ISAPP incorporates industry scientists in its activities and raises funds to advance its mission. However, no input into this consensus panel process was provided by members of the Industry Advisory Committee.

ISAPP functions as an independent, objective, science-based voice for the probiotic and prebiotic fields.

Panellists included experts involved with the original development of prebiotics and subsequent modifications of the definition.

Specialties included microbiology, nutrition, biochemistry and clinical research in both humans and animals. To prepare, panellists developed a discussion outline and target questions. Several delivered brief presentations that addressed background and core issues.

Discussion ensued for each issue until consensus was achieved. After the meeting, individual panellists wrote sections of the summary, which were compiled by G. S and G.

into a draft report. This document was edited and agreed upon by all panel members, and finally by the ISAPP board of directors. The finding that the colon was dominated by anaerobes, many of which obtain energy by fermenting substrates from the diet 9 , 10 , initiated research that played an important foundational part in many subsequent microbiome projects.

The prebiotic concept was initiated to build on the probiotic concept, the most widely accepted definition of which was proposed in Ref. Prebiotics target human-associated and animal-associated microbiota with the goal of improving health.

Whereas probiotics use live microorganisms, prebiotics are non-viable substrates that serve as nutrients for beneficial microorganisms harboured by the host, including administered probiotic strains and indigenous resident microorganisms.

Thus, prebiotics differ from most dietary fibres such as pectins, cellulose and xylans, which encourage growth of a wide variety of gut microorganisms. Our meaning here is that a prebiotic should not be broadly metabolized, but elicit a metabolism biased towards health-promoting microorganisms within the indigenous ecosystem.

The review by Simpson and Campbell 13 provides an overview of microbiota interactions and compares studies on fibre and prebiotics, concluding that prebiotics particularly FOS and GOS seem to promote increased abundance of bifidobacteria within the gut microbiota. Most of the first prebiotics assessed in humans and used commercially were shown to stimulate Lactobacillus and Bifidobacterium specifically, but not pathogens such as certain members of the Clostridia class and Escherichia coli 14 , 15 , As these genera were commonly used as probiotics, this approach provided a commonality between probiotics and prebiotics.

Thus, the prebiotic definition and the concept itself became imprinted in food, nutrition and microbiology fields Thus, it was implicit that trials to demonstrate prebiotic effects should be performed in the target host. In vitro assessments designed to identify pathways or mechanisms would not confirm prebiotic status in the absence of studies providing evidence of health effects in the host.

However, as prebiotic concepts evolved, so too did their application to extraintestinal sites. The Food and Agricultural Organization FAO of the United Nations UN organized a Technical Meeting to update the definition of prebiotics in Here, selective fermentation was removed as a criterion, but in doing so the definition was criticized for not excluding antibiotics.

Gibson et al. In , Bindels et al. This definition limited prebiotics to interactions with the gut microbiota excluding extraintestinal sites such as vagina and skin and removed the requirement for selective fermentation. Selectivity with respect to microbial fermentation is viewed by this panel as key to the prebiotic concept.

Importantly, however, this definition emphasized the functional effects of prebiotics on the microbiota. Given the proposed definitions already described, as well as others, the need for a consensus definition was evident This need was amplified by views that the prebiotic concept required clarification on specificity, mechanisms of effect, health attributes and relevance, with some authors being critical of concepts already put forward and its approaches 24 , 25 , Thus, the current ISAPP consensus panel now proposes the following definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit Box 1.

See Box 2 for additional rationale used to adopt this new definition. This term aligns with the word 'utilized' and implies 'for growth through nourishment', therefore excluding viable microorganisms and antimicrobial agents as prebiotics. Non-microbial effects do not fit with our current classification.

For the latter, these effects have tended to be researched in situations in which a resident microbiota is devoid or compromised. To confirm prebiotic traits, studies in the same species as the intended use are required. Although many microorganisms might be able to breakdown a given substrate, it is the resultant health benefit to the host owing to selective utilization by microorganisms that enables it to be termed prebiotic.

The actual mechanism of conferring benefit might also be mediated by microbial metabolic products. As such, both the microbiota changes and metabolites should be investigated, together with health outputs.

However, dietary prebiotics should still be non-digested by the host but utilized by the microbiota. An appropriate dose must be sufficient to generate a prebiotic effect, but not too high to induce unwanted or adverse effects such as excessive gas formation or non-selective utilization.

The 'adequate' dose will vary depending upon the microbial ecosystem and associated metabolic effects. Prebiotics are not the only substances that can affect the microbiota 10 Fig. The criterion of selective utilization distinguishes prebiotics from many of these other substances Hopefully, the new definition will readily enable a developer to know whether a new substrate fits the prebiotic category.

Prebiotics must be selectively utilized and have adequate evidence of health benefit for the target host. Dietary prebiotics must not be degraded by the target host enzymes. CLA, conjugated linoleic acid; PUFA, polyunsaturated fatty acid; FOS, fructooligosaccharides; GOS, galactooligosaccharides; MOS, mannanoligosaccharide; XOS, xylooligosaccharide.

PowerPoint slide. In previous iterations of the term prebiotic, 'selectively' was interpreted as referring mostly to lactobacilli and bifidobacteria. Specific stimulation of bifidobacteria bifidogenesis was considered a prebiotic effect.

Early research on gut microbial ecology was based on culture methods, which we now know were insufficient to reveal the complexity of prebiotic-induced microbial changes.

Molecular-based methods, which have since identified a broader range of members of the gut microbial community, have enabled the appreciation that more bacterial genera might utilize some prebiotic substrates, by fermentation and other metabolic pathways.

These microorganisms can vary depending upon the host and ecosystem under consideration. Hence, it is recognized today that prebiotic effects probably extend beyond bifidobacteria and lactobacilli, but to meet the selectivity criterion of a prebiotic, the range of microorganisms affected must be limited.

To this end, in two human studies that used high-throughput sequencing, bifidobacteria responded to prebiotic use 22 , However, other groups such as Faecalibacterium prausnitzii also increased in abundance in one trial 22 and in another study Anaerostipes spp.

were additionally elevated, whereas Bilophila spp. decreased Both studies used high-throughput sequencing to confirm selectivity of the prebiotic fermentation.

Selectivity does not necessarily mean effects on just one microbial group; a selective effect could extend to several microbial groups, just not all.

A prebiotic, in addition to having a selective effect on microorganisms, must also evoke a net health benefit. The guiding principles are that microorganisms affected and metabolites produced are considered to be beneficial and linked to a defined health aspect.

Envisaging every scenario is challenging. But, for example, is a product a prebiotic if its intake increases microbial production of butyrate? Short-chain fatty acids SCFAs , such as acetate, propionate and butyrate, and some other compounds, are recognized as having mechanistic links to health outcomes 28 , If the effect is a measurable benefit to host health, distinct from a control, it would constitute a 'prebiotic effect'.

To verify that the product itself is prebiotic, experiments would have to demonstrate that the product is selectively utilized, in this case by showing that a defined range of butyrate-producing microorganisms grow because of the product. Alternatively, the product might stimulate growth of other members of the microbiota, releasing metabolites that in turn stimulate butyrate production by other microorganisms.

This phenomenon could constitute a 'cross-feeding effect'. The net result is still selective in that propagation of particular microorganisms led to this overall health effect. However, if pathogenic microorganisms are involved in butyrate generation and a negative consequence occurs for the host, then it cannot be termed a prebiotic.

This distinction makes it important to determine both function and composition of the gut microbiota involved. Similarly, prebiotics for use in the gut microbiota of humans should not form gas distension issues after ingestion; as such, their fermentation must be selective and preferably include genera that are not gas formers such as Clostridium.

This consideration points unequivocally towards the need for selective metabolism. Notably, neither bifidobacteria nor lactobacilli manufacture gas in their metabolism Moreover, it is implicit that such influences on host health be determined in mixed microbial ecosystems containing the full microbiota of interest that is, in vivo.

Making inferences on prebiotic effects from pure or co-culture experiments is inadequate. Similarly, any conclusion regarding prebiotic activity must be based on an assessment of the full microbial diversity, not simply increased abundance of gut bifidobacteria or lactobacilli, for example.

The best techniques available need to applied, particularly as the microbiome field has benefited greatly from molecular-based technological advances. These techniques would include high-throughput sequencing, including metagenomics, which demonstrates quantifiable changes in the microbiota.

Similarly, metabonomic assessments, such as NMR or mass spectrometry, in appropriate biological materials can identify metabolic responses to prebiotics and help determine concomitant functionality of the microbiota.

A number of fermentable carbohydrates have been reported to convey a prebiotic effect, but the dietary prebiotics most extensively documented to have health benefits in humans are the non-digestible oligosaccharides fructans and galactans These oligosaccharides are preferentially metabolized by bifidobacteria A phenomenon explained by structure to function relationships; the linkage bonds in FOS and GOS can be readily degraded by degraded by β-fructanosidase β-galactosidase enzymes, respectively, which are prevalent in bifidobacteria.

This genus also seems to preferentially metabolize the chain length size typical of oligosaccharides; that is, a degree of polymerization DP between 4 and 30 Refs 31 , Importantly, having the appropriate transport machinery to capture and deliver these substrates into the microbial cytoplasm is a key requirement and contributes to the selectivity of prebiotics in the target sites 33 and emphasizes their ability to do so in a competitive environment in mixed culture ecosystems such as the human gut.

Substrates that affect composition of the microbiota through mechanisms not involving selective utilization by host microorganisms are not prebiotics. These substrates would include antibiotics, minerals, vitamins and bacteriophages, which are not growth substrates, even though their intake might alter microbiota and metabolic composition.

Certain soluble fermentable fibres are candidate prebiotics 34 , and some other types of dietary fibre can be prebiotic, provided that they are selectively utilized by the host microbiota and promote health.

Categorizing fibres as prebiotics is complicated by the fact that a dietary fibre can be a prebiotic in one host but not another. Furthermore, a substrate qualifying as a prebiotic might also depend on the target site.

For example, xylitol can be considered as a prebiotic in the oral cavity, but has not been shown to be prebiotic elsewhere 16 , Among the first group of substances recognized for their ability to influence gastrointestinal health were the oligosaccharides present in human milk.

Human milk oligosaccharides HMOs are particularly important for the development of the newborn baby's intestinal microbiota and metabolic and immunological systems, which have consequences for health later in life 36 , Consumption of mother's milk containing these HMOs clearly increases the proportion of HMO-consuming Bifidobacteriaceae and Bacteroidaceae Bifidobacterium longum subsp.

infantis B. infantis is the only Bifidobacterium spp. that has specifically evolved machinery to degrade the complete repertoire of HMOs. Other Bifidobacterium spp.

predominant in adults, mainly B. longum subsp. longum, B. adolescentis and B. lactis , lack many of the enzymes necessary to directly utilize HMOs effectively 38 , HMOs might indirectly affect composition of the intestinal microbiota by modulating immune responses and also have metabolism-independent mechanisms of action in the infant gut In particular, fucosylated and sialylated HMOs can prevent adhesion of pathogens to the intestinal epithelium through a competitive mechanism that ultimately protects the neonate from infection 41 , The main issues for this discussion are the following.

Is there evidence that HMOs confer a health benefit in humans through the host's microbiota selectively utilizing them, and therefore fulfilling the prebiotic definition?

And if compounds equivalent to HMO or bovine milk oligosaccharides, BMOs were to be produced by enzymatic synthesis, fermentation or extraction, could they still be considered as prebiotic? The ability of HMOs, BMOs or synthesized compounds to act as a substrate for the selective growth of beneficial bacteria, such as Bifidobacterium spp.

To confirm their status as a prebiotic, a controlled human study showing selective growth of bifidobacteria resulting in a health benefit is also needed. However, the use of such compounds for in vivo studies is limited to only a few reports.

However, effects on the microbiota were not reported in this study. The treatments were well tolerated and led to an increase in abundance of Bifidobacterium spp. Collectively, these studies provide an incomplete assessment of the prebiotic properties of these synthesized versions of HMOs.

infantis as well as some strains of B. longum and B. breve 46 , 47 , the ecological context that is, infants versus adults might dictate whether these HMOs are indeed prebiotic.

Moreover, having structural equivalence to specific HMOs does not infer functional equivalence to the constellation of HMOs in milk Thus, for now, it is acceptable to state that some HMOs are candidate prebiotics. Plant polyphenols constitute a class of compounds that can also meet the criteria of prebiotics, although far more studies in the target host are required.

Increasing evidence indicates that health benefits associated with polyphenol consumption depend on microbial utilization and the metabolites produced, rather than on parent compounds This evidence expands the prebiotic concept beyond non-digestible oligosaccharides such as FOS and GOS.

However, evidence for these emerging prebiotics is scarce relative to the fructans and galactans 16 and more studies measuring health benefits are required to fulfil their prebiotic status.

As selective utilization of a prebiotic by host microorganisms is key to its physiological effects, metabolic results of this utilization must, by deduction, be the main drivers. Some organic acids, for example, are principal end products of non-digestible carbohydrate or dietary fibre fermentation by host microorganisms.

These SCFAs are crucial for intestinal health and their activity can subsequently influence sites distant to the gut, with different SCFAs having varying functions. SCFAs can modulate certain aspects of metabolic activity including colonocyte function, gut homeostasis, energy gain, the immune system, blood lipids, appetite and renal physiology, as reviewed elsewhere 16 , 51 , Bifidobacteria, often stimulated by specific prebiotics, do not produce butyrate, so a probable scenario is that cross-feeding by other bacteria must have resulted in production of this SCFA.

Much has been reported about the benefits of butyrate in the gut and beyond 54 , leading to the potential of known butyrate producers such as Faecalibacterium prausnitzii , Eubacterium rectale or Roseburia spp. as possible probiotics and, therefore, new prebiotic targets.

By contrast, in the vagina, butyrate formation is more equivocal as 2-hydroxyisovalerate and γ-hydroxybutyrate have been associated with bacterial vaginosis Rather, lactic acid production and an increase in IL levels might be beneficial, indicating that prebiotics might be functional in the vaginal environment, because of their effects in the gut Lactulose, which has potential benefits in the gut and vagina, can increase lactic acid levels and decrease β-glucuronidase activity, considered beneficial for the host Owing to the anatomical proximity of rectum to vulva, some microorganisms capable of utilizing prebiotics in the gut are also present in the vagina, including Bifidobacterium and Lactobacillus spp.

Bile salt hydrolases are a family of enzymes produced exclusively by enteric microorganisms as a form of defence against their harsh, bile-rich environment. One study 62 showed that enhanced bacterial deconjugation of taurine from primary bile acids occurred in the presence of prebiotic inulin, supporting the theory that faecal bile acid profiling might be a useful biomarker for the intake of prebiotics in mice and potentially also in humans.

The net result of prebiotic utilization within the gut could also extend to health benefits elsewhere in the body.

For example, GOS stimulated growth of bifidobacteria in the mouse gut led to modulation of cortical IL-1β and 5-HT 2A receptor expression and reduced anxiety levels 63 , as well as enhancing brain barrier function in obese mice Similarly, utilization of prebiotics might also reduce blood ammonia levels and improve psychometric tests in patients with hepatic encephalopathy 65 , presumably through the formation of relevant bacterial metabolites.

Study findings suggest that prebiotics can reduce the development or severity of atopic dermatitis and eczema in children, presumably mediated by alterations to bacterial growth and interactions with the developing immune system, beginning in the gut 66 , The ability to increase water retention on the skin and reduce erythema formation is an emerging attribute of GOS ingestion, as reported in mouse studies On the skin, application of a prebiotic might stimulate changes in bacterial 69 or fungal 70 profiles perhaps by targeting epidermal growth factor receptor.

The health consequences of this approach are currently unclear, but might include psoriasis, acne, dermatitis, eczema and wound development 66 , 67 , Studies in mice have shown that oligofructose a fructan reduced diet-induced obesity, diabetes, hepatic steatosis and inflammation by mechanisms linked with changes in specific gut microorganisms and metagenomics functions of bacteria A study in rats suggested that oligofructose consumption might normalize the metabolomic signature of insulin resistance in obese rats and reduce obesity in offspring The ability to enhance secretion of satiety hormones peptide YY and glucagon-like peptide-1 might be an associated attribute of prebiotic intervention and related SCFA production 74 , 75 , In the mouth, compounds such as algal lectins, cranberry juice and cocoa polyphenols have been used to reduce the abundance of cariogenic bacteria.

However, these substrates do not function through being selectively utilized by beneficial host microorganisms in the mouth, so they are not prebiotics Short-chain GOS and long-chain FOS have been administered orally with B.

breve and were found to increase peak expiratory flow and reduce systemic production of type 2 T-helper cytokines after allergen challenge in adults with allergic asthma The proposed mechanism, whereby microbial utilization of GOS and FOS, presumably in the intestine, could lead to immunological modulation that enabled the host to cope better with allergen exposure in the lungs, was not identified.

In the nose and upper respiratory tract, bacterial species can be manipulated by prebiotics to influence health through immune reactions 79 or competition with aetiological agents of disease The ultimate goal of any intervention, including prebiotics, is to improve health and, therefore, reduce the risk or burden of disease.

The most effective approaches are those that rely on prevention and recognize that early-life strategies that promote a resilient, diverse and healthy microbiota have greatest long-term potential to benefit health 81 , Evidence for the important relationship between the structure and function of the microbial community, prebiotic use and host health has accumulated rapidly over the past decade 20 , 23 , To satisfy the criterion of conferring a health benefit, controlled studies establishing direct links between the prebiotic and health are needed in the target host.

The level of evidence should be commensurate with the strength of the health benefit claim. To date, numerous randomized controlled trials have shown health benefits of a variety of prebiotics across a range of populations, from healthy individuals to those with acute and chronic diseases.

These and other human studies have been summarized elsewhere and are not discussed in detail here, but key examples are listed in Table 1 Refs 16 , 65 , 67 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , , , , , , , , , , , , , , , , , , , , , Importantly, the effects of any intervention will be affected by a variety of host and environmental factors Thus, the effects of prebiotics have the potential to vary widely on an individual basis.

Microbial utilization of prebiotics can only occur if the appropriate bacteria are a component of the host's microbiota. This aspect might explain individual differences in responsiveness and in the outcomes of clinical trials.

Host factors include variation in genetic predisposition to diseases across multiple loci as well as specific polymorphisms in microbial recognition pathways that can influence colonization and its biological effects A number of environmental factors, including mode of delivery and early feeding, antibiotics, disease status and adult diet, can influence the human microbiome and possibly the effects of prebiotic supplementation , , , Prebiotics have been studied and used for companion animals, livestock, poultry and aquaculture.

The inherent differences among animal species with regards to living environment, anatomy and physiology, dietary composition and reliance on the gut microbiota for energy, must be considered when evaluating the effect of prebiotics on animal health Table 2 provides examples of the use of prebiotics in animals.

Dogs and cats evolved as Carnivora eating diets high in protein and fat but low in fibre They are non-ruminants with short, simple gastrointestinal tracts that have little capacity to ferment non-digestible substances, which predominantly occurs in the colon Nevertheless, some health benefits have been achieved with prebiotic administration such as reduced infections, improved insulin sensitivity and better faecal consistency , , , , Prebiotics such as oligosaccharides of fructose, mannose and chitin protect piglets against high environmental stressors such as antibiotics, etc.

and pathogen loads, including faecal E. coli shedding, and reduced infection-associated responses to Salmonella enterica serovar Typhimurium infection or porcine reproductive and respiratory syndrome virus , , , Calves are born in a pre-ruminant state and function as non-ruminants until the rumen and other compartments of the stomach fully develop During the first few weeks of life, or longer in the case of veal calves maintained on low-roughage diets that is, low in fibrous material , prebiotics can be used to increase growth, improve feed conversion ratio, reduce the incidence and severity of scours diarrhoea or reduce the incidence of respiratory diseases , , , Poultry, which are used primarily for the production of meat or eggs, include landfowl for example, chickens, turkeys and quail and waterfowl for example, duck or geese species, respond to prebiotics despite most having a fairly short midgut and hindgut that includes a short, straight colon and twin caeca Dietary prebiotics, including inulin, yeast cell wall extracts, lactulose and GOS are usually fed at concentrations up to 0.

Farmed aquatic species include finfish and shellfish. Although anatomy varies among carnivorous for example, turbot , omnivorous for example, catfish and herbivorous for example, sturgeon species, all fish have a fairly simplistic and short gastrointestinal tract , , The short length and simple structure lack of special adaptations of the fish gut results in the rapid transit of digested material, limiting the time available for microbial or prebiotic activity.

Horses are large non-ruminant herbivores that rely heavily on microbial fermentation for energy, with more than half of their maintenance energy requirement coming from microbial fermentation occurring in their enlarged caecum and colon As their typical diet is high in roughage and feedstuffs that are consumed throughout the day, prebiotic interventions might help improve effectiveness of fermentation , , Developing a consensus definition of prebiotic is useful for many stakeholders Fig.

Agreement on this definition will reduce misinformation and confusion among consumers and health-care providers, facilitate sensible regulatory approaches, and provide common terminology and scope for future prebiotic research.

This consensus definition should enable consumers to understand the terms used on product labels. Proper use of the terms by all stakeholders will help avoid misleading messaging. Although consumers might not be expected to understand the mechanistic details for how prebiotics function to improve health, our proposed definition should be readily appreciated.

Individuals can respond variably due to their habitual diets, host microbiota, host genetics to different prebiotics. This aspect dovetails with the concept of individualized nutrition, which should be understood by consumers. Media and publishers of scientific papers. The media press, TV, web-based and others should avoid use of headlines that misrepresent results.

Presentation of association studies as if they contribute to an understanding of causality can be especially misleading. When discussing results of a single study, how that study fits into the totality of evidence for that topic should be reported, including null results. The media should use the term prebiotic consistent with this proposed definition.

Regulators have primary responsibility for ensuring safety of marketed products and protecting consumers from fraudulent marketing. To accomplish these goals, they are bound by statutes and regulations adopted in their respective regions.

Acceptance by regulators of the consensus definition of prebiotic would make it clear what can be expected of these substances from a scientific basis, and whether the term is being used appropriately.

For example, most prebiotics for the gut require an oral dose of upwards of 3 g per day to elicit an effect Products containing doses lower than this level should not be called prebiotics, unless such a low dose has been proven to elicit selective effects upon the microbiota and concomitant health aspects.

Incorporating a health benefit in the definition gives a tangible end point for producers and regulators alike to use in their assessment of whether a novel product fulfils the criteria. Scientists have the responsibility of considering all aspects of research on prebiotics structural biochemistry, clinically relevant end points, effective dose, mechanisms of action, analytical methods and consolidating findings such that a clear description of outcomes can be attained.

Future prebiotic research should strive to confirm causality between an observed health benefit and microbiota-mediated mechanisms. This confirmation of causality has been challenging to achieve and some assumptions might be necessary, as is the case for most pharmaceutical interventions.

To this end, well-controlled, placebo, blinded in vivo studies that exploit the latest multi-omic technologies are necessary. For example, in the case of a dietary prebiotic for humans, a full assessment of gut microbiota changes using robust molecular procedures that are fully and accurately quantifiable is required, such that selective substrate use can be ascertained.

This analysis would be coupled with metabolic assessments of functionality for example, metabonomics applied to blood, urine and faeces. In patients, symptomology should be determined, and in healthy or 'at-risk' populations reliable biomarkers of beneficial effects must be identified and measured.

These biomarkers could include immunological changes, inflammatory mediators, serum lipid levels, genotoxicity, toxicity and cognitive function, among others, as appropriate to the study population.

The study population must be reflective of the condition being researched, and an appropriate power calculation used to determine volunteer numbers.

An effective prebiotic dose and duration must be established to compare effects. The test delivery vehicle for example, foods such as cereal, bread or juices should be considered such that prebiotic potential is not compromised.

Exclusion and inclusion criteria are applied to control for fluctuations in diet and other major lifestyle changes. Following that, if the only discernible correlation is an improvement in health indices with selective microbiota changes composition and function then it could be assumed that two are inter-related and driven by the prebiotic.

When communicating results, scientists should be careful to present data in a manner that does not mislead readers. Suppliers or manufacturers of prebiotics. Suppliers and manufacturers have the responsibility to accurately characterize the identity of their prebiotics and conduct research to evaluate health benefits and safety.

They should be committed to high-quality, controlled, non-biased studies that assess effects on clinically relevant outcomes with associated peer-reviewed publication of the findings.

They need to provide accurate technical information to end-product manufacturers. End-product manufacturers. Producers of consumer products have a special responsibility to formulate and label prebiotic products in a manner that is true to the definition proposed herein, does not overstate the strength of evidence for health benefits and is consistent with dose and form used in efficacy studies.

Producers can contribute by sponsoring research on health benefits of their final products. Advertising must be consistent with scientific definitions, not overstate the strength of evidence for health benefits and adhere to regulatory standards.

Health-care providers and standards or recommendation-setting organizations. By providing compelling data that prebiotics can improve health, it is hoped that clinical organizations will accept and use the new definition, review the data in totality and develop evidence-based recommendations.

This approach will help health-care providers to make decisions about clinical use in the absence of formal recommendations based upon their own risk—benefit analysis. We anticipate that future prebiotic products will expand current applications, include products administered to many body sites and be developed as non-conventional or novel foods, pharmaceuticals or other categories.

In this section further insights into regulatory considerations in two jurisdictions are provided as examples, but the way that prebiotics are regulated will differ in other countries. European Union. In the European Union EU , any health message carried by food requires assessment of the science by the European Food Safety Authority EFSA and authorization by the European Commission.

Some prebiotic health claims have been approved, for example chicory inulin Inulin, FOS and GOS were used in the EU before and are considered safe food ingredients. However, prebiotic substances created after are considered novel and require safety clearance, a designation given, for example, to specific HMOs.

Additional product approvals hopefully will be forthcoming, once relevant evidence is available, aided by the contents of this consensus document. When prebiotics are considered to be novel foods, challenges arise to assessments as a food or individual ingredient.

The EU considers HMOs added to a food as novel food ingredients, a legal construct determined by law A FOS or GOS with a markedly altered DP or with a different source or production method might be regarded as a novel food.

An additional factor in the EU is the new consideration of safe history of use in countries outside the EU Prebiotics is not yet a term recognized by the FDA. Prebiotics are regulated based on the category of product their intent and design dictates. Most prebiotics are sold as ingredients for foods including infant formula or are dietary ingredients in dietary supplements.

The FDA issued an updated guidance to industry on the new dietary ingredient notification process in Ref. Other regulatory categories that might apply to prebiotics are medical foods, drugs, cosmetics or devices developed for humans or animals.

Changes to fibre labelling regulations in the USA in in part owing to the different methods of analysis of fibre worldwide will probably affect carbohydrate-based prebiotics In the past, various analytical methods determined fibre levels in foods.

Prebiotics, detected as soluble fibre, could be listed as fibre on the nutrition facts label. Under the new regulations, this listing will not be allowed. Fibre has been redefined to be soluble and insoluble non-digestible carbohydrates with three or more monomeric units and lignin that are intrinsic and intact in plants, and certain isolated and synthetic non-digestible carbohydrates with three or more monomeric units.

Some prebiotics, such as inulin, fall under the latter category, but even so were not granted status as a fibre by the FDA. The new rules require that for a prebiotic to be listed as fibre, it must confer a beneficial physiological effect and this evidence must be submitted to the FDA either though the citizen petition process or the health claims petition process for the FDA to authorize the health claim.

The FDA has promised further guidance on this topic. This paper describes conclusions of a consensus panel of experts regarding a definition of prebiotic and the rationale for that definition. It is hoped that this new definition and explanation will clarify what is required to call a substance a 'prebiotic'.

Given that differences exist across animal species, prebiotic efficacy, safety and appropriate dosing should be demonstrated for the specific target host. In conclusion, prebiotics have the potential to improve human and animal health and reduce risk of diseases mediated by microbiota aberrations.

The field would greatly benefit from research focused on mechanisms of action, characterizing responders or non-responders, understanding how structure relates to function of prebiotic substances and correlating that function to health outputs. The use of prebiotics to improve health cannot be, and should not be, viewed in isolation, and will be part of a wider approach for healthy nutrition and lifestyle.

The capacity exists for prebiotics to be used therapeutically in the management of disease and to preventively promote health. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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PLoS ONE 3 , e Paulino, L. Molecular analysis of fungal microbiota in samples from healthy human skin and psoriatic lesions. Campananti, A. Maintaining good gut health is important, and probiotics, prebiotics, and synbiotics can play a crucial role in achieving this. For people with certain digestive conditions or taking antibiotics, adding probiotic supplements to their diet may help alleviate related symptoms.

However, it is important to be aware that probiotic supplements also carry potential risks. They can cause allergic reactions and may lead to digestive issues such as bloating, gas, diarrhea, or constipation, especially for those with preexisting immune system or health concerns.

Follow her on Instagram for more nutrition tidbits. Nirali is a Program Assistant with Nutrition Services at the Department of Recreational Sports. She is a 3 rd -year dietetics major with a minor in health promotion.

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Probiotics — The Beneficial Bacteria Probiotics are live microorganisms that provide health benefits to their host when consumed in adequate amounts.

Health Benefits of Probiotics Probiotics have been associated with a range of health benefits, including improved digestion, a strengthened immune system, and potential mental health benefits Ansari et al.

Prebiotics — The Nourishment for Good Bacteria Prebiotics are non-digestible fibers and compounds that selectively serve as food for probiotics and other beneficial gut bacteria. Health Benefits of Prebiotics Prebiotics have been linked to improved gut health, enhanced mineral absorption, and a reduced risk of certain chronic diseases.

Synbiotics — The Dynamic Duo Synbiotics are a combination of probiotics and prebiotics designed to work together synergistically. So, What Now?

MSU researchers Prebiotics and reduced risk of disease discovered reducef the use of a prebiotic Prebiotice help reduce the occurrence of certain kinds of cancer. Researchers at Michigan State University MSU have Muscle recovery support that a disdase may Oxygenation supplements for athletes the diseasw natural killer dissase fight bacterial infection and reduce inflammation, greatly decreasing the risk of Prdbiotics cancer. Prebiotics and reduced risk of disease are fiber supplements that serve as food African mango extract for immune support the trillions of tiny bacteria living in the gut. When taken, they can stimulate the growth of good bacteria. The evolution of prebiotic supplements as well as probiotics, which are actual bacteria ingested into the system provide new therapeutic avenues for researchers and physicians. In research published in the April edition of the Journal of NutritionMSU AgBioResearch scientist Jenifer Fenton reports that mice given the prebiotic galacto-oligosaccharide, or GOS, saw the severity of their colitis one of the main forms of inflammatory bowel disease significantly reduced. In fact, the mice fed GOS — a synthetic compound that is known to stimulate beneficial bacteria and is found in foods such as biscuits and infant formula — saw a 50 percent reduction in colitis. Prebiotics and reduced risk of disease

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