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Author's Accepted Manuscript: Food Bioscience
Author's Accepted Manuscript: Food Bioscience
www.elsevier.com/locate/sdj
PII: S2212-4292(17)30845-3
DOI: https://doi.org/10.1016/j.fbio.2018.10.008
Reference: FBIO348
To appear in: Food Bioscience
Received date: 8 November 2017
Revised date: 13 October 2018
Accepted date: 14 October 2018
Cite this article as: Debapriya Mohanty, Snigdha Misra, Swati Mohapatra and
Priyadarshi Soumyaranjan Sahu, Prebiotics and synbiotics: Recent concepts in
nutrition, Food Bioscience, https://doi.org/10.1016/j.fbio.2018.10.008
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Prebiotics and synbiotics: Recent concepts in nutrition
1
Department of Microbiology, Centre for Post Graduate Studies, Orissa University of
Agriculture and Technology, Bhubaneswar, Odisha 751003, India
2
Division of Nutrition and Dietetics, School of Health Sciences, International Medical
University, 57000, Kuala Lumpur, Malaysia
3
Department of Biotechnology, Amity University (AIMT), Noida, 201313
Uttar Pradesh, India.
4
Division of Pathology, School of Medicine, International Medical University, 57000, Kuala
Lumpur, Malaysia
Abstract
Gut flora have a crucial role in metabolizing various nutritional substrates to maintain human
health. Several studies on prebiotics and symbiotic have reported to be clinically effective in
maintaining the balance of gastrointestinal microbiota to improve health conditions. Therefore,
an optimum balance is required in the intestinal microflora of the host. Under certain stress
conditions, it may be altered which manifests as gut disorders. Prebiotics from food are the
fermentable fiber which selectively feed beneficial bacteria in the intestinal microbiota, to
maintain a healthy microbiome environment. Probiotic foods are supplements with live
microbes, showing immune-supportive effects in the gastrointestinal tract. However, both pre-
and probiotics have been reported to work best in combination. This combined effect of both,
1
results in synbiotics. Prebiotic foodstuff remains unaltered in the gastrointestinal tract, as gastric
enzymes cannot act on them. They reach the large intestine intact and are selectively fermented
to give beneficial effects. This review focusses on prebiotic foods, their nutritional value,
characteristics, safe consumption, therapeutic effects and mechanism of action and their role in
synbiotics.
1. Introduction
There has been a paradigm shift in food culture across the globe. Modernization has led
to transitions in food habits. With an increased consumption of fast foods with decreased
physical activity, there has been a sudden surge in the rise of non-communicable diseases (NCD)
(Prescott, 2014). Particular attention must be drawn to the composition and safety of processed
foods that contribute to NCD. The introduction of prebiotics in processed foods may be a
possible solution. The International Scientific Association for Probiotics and Prebiotics (ISAPP)
defines a prebiotic as “a substrate that is selectively utilized by host microorganisms conferring a
health benefit”. This definition expands the concept of prebiotics to include non-carbohydrate
substances, applications to body sites other than the gastrointestinal tract, and diverse categories
other than food. The consensus definition also applies to prebiotics for use by animals, in which
microbiota-focused strategies to maintain health and prevent disease is equally relevant as
humans (Gibson et al., 2017). Prebiotics are non-active food constituents that moves to the colon
and are selectively fermented. They are colonic foods that enter the large intestine (colon) and
serve as substrates for endogenous colonic bacteria; mostly bifidogenic and lactic acid bacteria in
the gastrointestinal (GI) tract to provide the host with essential nutrients and energy (Gourineni
et al., 2011; Salvini et al., 2011). Prebiotics are often, relatively short chained, low molecular
weight carbohydrates that are not digestible by digestive enzymes in humans; and beneficially
manipulated in the composition and/or activity of colonic microflora. They improve the host’s
health and are antagonistic to pathogenic organisms limiting their proliferation. Thus, the
prebiotic approach uses the administration of non-viable entities. Prebiotics have the ability to
2
improve the survival, growth, metabolism and beneficial health activities of probiotics in the
digestive system (Sekhon et al., 2010).
The synergistic combination of prebiotics and probiotics found in products such as foods,
drugs, and supplements is known as “Synbiotics” (live cells of the useful microbes/probiotics
and a selective substrate/prebiotic). In other words, synbiotics is defined as “a combination of
probiotics and prebiotics that beneficially affects the host by improving the survival and
implementation of live microbial dietary supplements in the GI tract”. Synbiotics have a greater
efficacy, as compared to either probiotic or prebiotic used in isolation. Functional petit-Suisse
cheese and ice creams supplemented with L. casei and 2.5% inulin are effective synbiotic
products (Criscio et al., 2010). Various combinations of synbiotics show therapeutic effects
against diseases, like gastrointestinal diseases, respiratory infections, hypercholesterolemia,
atopic dermatitis, allergy, diabetes, liver diseases and cancer (Ogawa et al., 2006; Passeron et al.,
2006; Cazzola et al., 2010; Ooi et al., 2010; Rayes et al., 2012; Dinleyici et al., 2013).
2. Sources of prebiotics
Legumes, fruits and vegetables, such as wheat, oatmeal, barley, navy beans, white beans,
black beans, lentils, kidney beans, chickpeas, tomatoes, onions, garlic, chicory, greens, leeks,
shallots, asparagus, spinach, Jerusalem artichokes, bananas and berries are rich in prebiotic
fibers. (Crittenden and Payne, 2008). Generally, the beneficial prebiotic agents are categorized as
polyols (sugar alcohols), oligosaccharides and soluble fiber (Table 1).
2.1. Polyols
Xylitol, sorbitol, mannitol, lactulose and lactilol are widely used prebiotic polyols (Venter, 2007;
Spindler-Vesel et al., 2007).
2.2. Oligosaccharides
Oligosaccharides are the combinations of sugars with a different degree of polymerization and
considered as major sources of prebiotics. They are non-digestible; hence, are available for
hydrolysis by hydrolytic enzymes in the colon and favor the growth of beneficial bacteria over
that of harmful ones. Examples of prebiotic oligosaccharides are; fructo-oligosaccharides
(FOS), galacto-oligosaccharides (GOS), soy-oligosaccharides (SOS), isomalto-oligosaccharides
(IMO), oligosaccharides (OS), transgalacto-oligosaccharides, xylo-oligosaccharides (XOS),
inulins, raffinose lactosucrose, palatinose, oligofructose (OF), galactosyl lactose and
3
pyrodextrins (Venter, 2007; Spindler-Vesel et al., 2007; Al-Sheraji et al., 2013). FOS are found
in plants such as onion, garlic, asparagus, chicory, sugar beet, tomatoes, banana, Jerusalem
artichoke, honey, wheat, oat, barley and soybean asparagus whereas human milk and cow’s milk
are the major sources of GOS (Alander et al., 2001). XOS are found in fermented foods such as
fruits, vegetables, milk, honey and wheat bran. Additionally, miso, soy, sauce, sake, sugarcane
juice and honey are foods containing IMO and isomaltulose in abundance. Inulin is a blend of
fructan chains widely distributed in various plant species, e.g., garlic, onion, asparagus, chicory,
artichoke and wheat. The majority of inulin commercially available today is extracted from
chicory roots. Inulin and OF have a specific chemical structure which is metabolized as dietary
fibers in the human body showing the same beneficial dietary fiber effects (Al-Sheraji et al.,
2013).
2.3. Fibers
Although all prebiotics are fiber, not all fibers are prebiotics. The grains, legumes, flours,
potatoes, vegetables and fruits are the most popular sources of dietary fiber. Dietary fibers are
non-digestible carbohydrates, mainly, several non-starch polysaccharides such as cellulose,
dextrins, pectins, beta-glucans, waxes, and lignin. They show similar physiological effects on
human health as that of inulin-type fructans (Slavin, 2008; Napolitano et al., 2009). Therefore,
dietary fibers are a good source of prebiotics. The classification of the dietary fibers is presented
in Table 2.
2.4. Other food supplements with prebiotic properties
Some novel sources of food supplements are capable of stimulating the growth of beneficial
microflora in the GIT and as effective prebiotic sources. Examples of the novel sources of
prebiotics, in the microbiome environment in human intestines are: Lupin kernel fiber, a
legume-derived food (Smith et al., 2006); aqueous extracts of blueberry, selenium-containing
green tea (SGT) and China green tea (CGT) (Molan et al., 2009a; 2009b); Indian mulberry
(Yang et al., 2011b); mushrooms (Synytsya et al., 2009); dragon fruit (Wichienchot et al., 2010)
and Yacon root (Ojansivu et al., 2011). Lupin kernel fiber enhances the growth of
Bifidobacterium spp. by suppressing the levels of the Clostridia, e.g., C. ramosum, C. spiroforme
and C. cocleatum (Smith et al., 2006). The aqueous extract of blueberry and SGT modulated the
activity L. rhamnosus and Bifidobacterium breve in addition to having higher DPPH free-radical
scavenging activity (Molan et al., 2009a; 2009b).
4
3. Characteristics of beneficial prebiotics
The prebiotic activity reflects the ability of a given substrate to support the growth of
probiotics. Both in vitro and in vivo methods are available to show this resistance in the
candidate prebiotic. Thus, stimulation of probiotic activities has been identified as one of the
characteristics of beneficial prebiotic selection (Seifert and Watzl, 2007; Wang, 2009). The
characteristics of beneficial prebiotics are summarized in Table 3.
5
for cardiovascular health. Replacement of sheep milk fat by prebiotics to manufacture sheep milk
ice cream can be an effective alternative to improve the nutritional and physiological aspects due
to its low caloric value and functionality provided by prebiotics (Balthazar et al., 2017). Thus,
the demand for functional dairy products has led to the reduction and replacement of fat content
by prebiotic fibers in the formulations. The supplementation with prebiotic dietary OS can add
value to the product by providing a functional appeal.
Prebiotin, a prebiotic fiber powder is rich in OF and inulin. It stimulates the growth of
beneficial bacteria throughout the colon. MSPrebiotic® is 70% dietary fiber, which is a simple
and easy solution to bridge the fiber gap. It promotes regularity, maintains heart health, and
reduces inflammation.
Buckwheat diet (Prestamo et al., 2003), a cake containing barley β-glucan (Mitsou et al., 2010),
peach-flavored yogurt containing a prebiotic (Gonzalez et al., 2011), drinkable yogurt with
6
prebiotics, e.g., soluble corn fiber, polydextrose and chicory inulin (Allgeyer et al., 2010)
showed beneficial health effects. Some other examples are shown in Table 4.
7
flora (Bodera, 2008). Passariello et al (2011) evaluated the efficacy of zinc and prebiotics (FOS
and XOS) fortified oral rehydration solutions (ORS) for treatment of diarrhea among children
over 72 h. They reported that a zinc and prebiotic combination reduced the duration of diarrhea
in patients by stimulating water and electrolyte re-absorption across gut mucosa and inhibited the
pathogens.
7.2. Antipathogenic effect
The potential use of prebiotics has been reported in experimental and animal studies, with
respect to gastrointestinal infections. They have an ability to protect against a variety of potential
pathogenic bacteria, such as Salmonella enterica serovar typhimurium (S. Typhimurium) ,
Listeria monocytogenes and Escherichia coli by following several mechanisms such as
production of inhibitory factors (bacteriocin, short chain fatty acid (SCFA)), colonization
resistance and competitive exclusion (Vamanu and Vamanu, 2010; Licht et al., 2012; Patel and
Goyal, 2012).
Vamanu and Vamanu (2010) studied the effect of prebiotics, e.g., inulin from chicory and
dahlia, raffinose and lactulose on the synthesis of bacteriocins from Lactobacillus paracasei
CMGB16 strain. They observed a significant increase of the activity of the bacteriocin when the
media was supplemented with inulin, lactulose and raffinose (after 25 - 96 h). Prebiotic sorbitol
has a positive influence on bacteriocin production from Pediococcus acidilactici LAB 5 isolated
from meat (Mandal et al., 2009).
Prebiotics improve the growth and functions of colonic microbiota during their
fermentation. Lactates, SCFA such as acetate, propionate and butyrate are the end products of
metabolized prebiotics. SCFA have an important role in the mechanism responsible for
inhibiting enteropathogens by lowering the pH of GI tract. This low pH may reduce the peptide
degradation. The toxic compounds like ammonia, amines, and phenolic compounds are acted
upon by bacterial enzymes to prevent their harmful effects. SCFA stimulates the growth of
colonic crypt cells, decreases the risk of mutations in the intestine, helps in protein synthesis
resulting in increased microbial biomass (Fooks and Gibson 2002; Cavaglieri et al., 2003; Coles
et al., 2005). SCFAs can bind G-protein coupled receptor 41 (Gpr41), a strong regulator of host
energy balance whose effects are dependent upon the gut microbiota (Samuel et al., 2008).
Generally, butyrate is an energy source for colonocytes and can also maintain a normal
8
colonocyte population, preventing mutations. Thus, it functions as a primary protective factor
against colonic disorders (Vernazza et al., 2006).
Some prebiotics (GOS) showed an anti-adhesive effect on harmful microbes in the GI
tract. OS acts as a molecular receptor decoy that can competitively inhibit bacterial adhesion and
also as a repressor of virulence factors by repressing the gene expression in some
enteropathogens. They can adhere to the binding sites of bacteria on the enterocyte surface
resulting in blocking the adhesion of pathogenic bacteria to intestinal epithelial cells (Shoaf et
al., 2006). Certain milk-derived OS structurally resemble the saccharide containing glycoproteins
that many pathogens bind to, in the intestinal cells. These may act as a receptor analogue and
thereby inhibit infection, if the pathogenic cell binds to the oligosaccharides rather than to host
cell receptors. Several studies with different preparations of GOS consistently show that, in vitro,
the prebiotic has the potential to reduce adherence of enteropathogenic E. coli, as well as
Salmonella to epithelial cell lines. Also non-milk derived prebiotics have been shown to inhibit
infection though direct interaction with the pathogen. Pectins and pectic OS were reported to
reduce the activity of shiga like toxins produced by E. coli O157:H7, likely by inhibiting binding
of the toxin (Licht et al., 2012). Evidence shows an improved efficacy of zinc and prebiotics
(FOS and XOS) fortified ORS for treatment of diarrhea in children (Passariello et al., 2011).
FOS is reported to be effective in preventing relapse of C. diffecile associated diarrhea (Saad et
al., 2013). Earlier studies have demonstrated that prebiotics also exert their effect beyond the GI
tract (Lenoir-Wijnkoop et al., 2007).
7.3. Anti-cancerous effect
Prebiotics have a protective effect against carcinogens involved in colon cancer (Hsu et al.,
2004). SCFA, such as propionate, has an anti-inflammatory effect on colon cancer cells. Butyrate
obtained from fermentation of GOS regulates the apoptosis and reduces metastasis in colon cell
lines. It also protects the body from carcinogens by enhancing expression of enzymes involved in
detoxification (Nurmi et al., 2005; Pool-Zobel, 2005; 2007). Butyrate suppressed the expression
of transcription factor NF-jB in HT-29 cell lines, whereas acetate increased the peripheral blood
antibody production and natural killer cells (NK) activity in cancer patients (Macfarlane et al.,
2008; Patel and Goyal, 2012).
9
7.4. Immune-modulatory effect
Prebiotics have an important role in modulating the immune system and enhancing host defences
(Lomax and Calder, 2008; Macfarlane et al., 2008). Vos et al. (2010) studied the immune-
modulatory effect of specific prebiotic OS, e.g., GOS, FOS and pectin-derived acidic OS. The
administration of prebiotics enhanced the production of anti-inflammatory cytokines by
suppressing pro-inflammatory cytokines that led to a decrease in overall gut inflammation
(Schiffrin et al., 2007; Vulevic et al., 2008; Patel and Goyal, 2012).
10
prebiotic carbohydrates on infectious diseases in human subjects. Some of these studies are
summarized in Table 6.
The action of prebiotics improved in the presence of probiotics. Probiotics are live
microorganisms when administered in adequate amount and have conferred health benefits.
Hence, both probiotics and the prebiotics work together to prevent any altered health condition.
Synbiotics
Synbiotics are essentially a synergistic combination of probiotics and prebiotics, with
therapeutic effects. Prebiotics promote the growth of probiotics in the colon. Hence, synbiotics
are essential for good colonic health, prevention of disease, and/or as alternatives for reducing
the risk associated with diseases.
11
of the products. GBF is an alternative ingredient in fermented milk formulations, contributing as
a functional food, particularly as a synbiotic product (Batista et al 2017).
12
A combination of Bifidobacterium lactis HN019 and prebiotic oligosaccharide reduced
the incidences of dysentery episodes, pneumonia, and respiratory infection in lowering childhood
morbidities (Sazawal et al., 2010). Progressive studies in the field of synbiotics established that
the use of a combined supplement of Lactobacillus plantarum299 and fiber prevents bacterial
infections after liver transplantation and enhanced liver function capacity (Rayes et al., 2012).
Synbiotic 2000, L. rhamnosus GG and Bifidobacteria subsp. lactis and OF-enriched inulin are
efficient synbiotics against colon cancer (Cazzola et al., 2010) whereas L. acidophilus CHO-220
and inulin together show advantageous health effects on hyperlipidaemia (Ooi et al., 2010).
Conclusion
This review presents the therapeutic properties of prebiotics and synbiotics, showing their
efficacy in the systemic health, metabolism and immune system. Identification of the prebiotic
coupled with the potent probiotic will result in effective synbiotics. Potential advantages of using
prebiotics and synbiotics from a health standpoint, includes partial replacement of antibiotic
growth promoters. Prebiotics, especially inulin-type fructans (also synbiotics) are good
candidates to be classified as functional food ingredients. However, to affirm the findings of this
review more clinical trials are suggested.
Conflicts of interest and financial disclosures: The authors declare no conflict of interest.
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Table 1 Source and classification of prebiotics
Class of prebiotic Types of prebiotics Food sources
1. Polyols (sugar alcohols) Lactulose Lactose (milk)
Soy-oligosaccharides Soybean
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galactosyl lactose and
pyrodextrinsare
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Table 2 Classification of dietary fibers
Category Examples
Dietary fiber Lignin, cellulose, β-glucans, hemicelluloses, pectins and gums
Functional fiber Fructooligosaccharides polydextrose, isolated gums
Soluble fibers Pectin, β –glucans, gums, wheat dextrin and psyllium
Insoluble fibers Cellulose, lignin
Fermentable fibers Pectin, inulin, β –glucans
Non-fermentable Cellulose, lignin
fibers
Viscous fibers Pectins, β-glucans, psyllium, glucomannan
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Table 3 Characteristics of beneficial prebiotics
Criteria
1. Must be edible parts of plants
2. Should be carbohydrates comprising of a mixture of oligosaccharides/ and
polysaccharides
3. Must be resistant to gastric acidity and hydrolysis by mammalian digestive enzymes
4. Should not get absorbed in the upper part of the gastrointestinal tract
5. Must encourage beneficial luminal/systemic effects within the host by fermentation
6. Should not be metabolized by the host
7. Should selectively stimulate the growth and/or activity of health promoting intestinal
bacteria and probiotic strains to become metabolically active
8. Must be beneficial to the host health
9. Must be excreted as such in the urine
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Table 4 Examples of commercially available prebiotic supplements
31
weight
32
(FOS) pathogens by following
competitive exclusion
B. Increases SCFA such as
acetate, propionate and butyrate in
the large bowel
C. Reduces damage of ulcerative
colitis
33
oligosaccharides health
34
treatment period
Mice Candida Inulin 6 wk Lowered densities of C.
albicans
or before challenge albicans in the small intestine
L.
monocytogenes, FOS in intervention groups
S.Typhimurium
Lowered mortality from L.
monocytogenes in mice fed
FOS and especially inulin
Lowered mortality from S.
typhimurium in mice fed
inulin
Rats S. enteritidis FOS , 2 wk Enhanced translocation
lactulose, before challenge of Salmonella
resistant
starch, wheat
fibers or
cellulose
Rats S. enteritidis FOS 2 weeks Increased translocation of
before challenge Salmonella
Guine L. Either XOS, 3 weeks Lowered prevalence of
monocytogenes
a pigs GOS before Listeria in intestinal samples
(mix of 3
strains), challenge and in liver, spleen and
oral infection
mesenteric lymph nodes
(Source: Licht et al., 2012)
b. Human studies
Type of Challenge Prebiotic Treatment Effects
study treatment period
Prospective, Infants with Mixture of short- First 6 Reduced in number of
parental
randomized, chained GOS months infectious episodes and
history of atopy
double- and long-chained of life in the incidence of
35
blind, FOS recurring infections
placebo- during first 6 months of
controlled life
study
Double- Healthy infants FOS In diet for Decreased in pathogenic
aged
blind 21 days clostridia and lower
7-19
placebo incidence of diarrhea
controlled during supplementation
36
study
37
Figure 1 Legend: Schematic representation of direct and indirect mechanism of action by the
prebiotics on host health
38