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Dietary fibers, prebiotics, and exopolysaccharides produced by

lactic acid bacteria: potential health benefits with special regard

Food & Function Accepted Manuscript

Received 19th January 2018,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
to cholesterol-lowering effects
E. Korcz,ab Z. Kerényib and L. Vargaa
The gastrointestinal (GIT) microbiota, which plays a crucial role in human health, is influenced by a number of factors
including diet. Consumption of specific dietary ingredients, such as dietary fibers and prebiotics, is an avenue by which the
microbiota can be positively modulated. These substances may also reduce serum cholesterol levels through various
mechanisms. Interest has increased in methods of reducing blood cholesterol level, because dyslipidemia is recognized as
a contributory risk factor for the development of cardiovascular diseases. Several drugs have been developed for the
treatment of hypercholesterolemia; however, undesirable side effects were observed, which have caused concerns about
their long-term therapeutic use. Alternatively, many nonpharmacological approaches were tested to reduce elevated
serum cholesterol levels. Dietary fibers and prebiotics have particularly beneficial effects on the GIT microbiome, and can
also reduce serum cholesterol level through various mechanisms. Lactic acid bacteria (LAB) are potentially capable of
synthesizing various polysaccharides, e.g. exopolysaccharides (EPS), which may play a role as prebiotics. LAB-based EPS
have the potential to affect the gastrointestinal microbiome and reduce cholesterol. However, as dietary fibers comprise a
complex group of substances with remarkably diverse structures, properties, and impacts, EPS also differ greatly and show
a multitude of beneficial health effects. This review discusses the current knowledge related to the effects of dietary fibers
and prebiotics on the human GIT microbiome, the prebiotic properties of EPS produced by LAB, and the health-promoting
benefits of these polymers with special emphasis being given to cholesterol lowering.

Introduction
The human gastrointestinal (GIT) microbiome is one of the
most densely populated microbial communities on earth. It
contains highly diverse microbial populations that provide
metabolic, immunologic, and protective functions, thus playing
an essential role in human health. The GIT microbiota is
influenced by a number of factors including genetics, host
physiology, and environmental factors, i.e. living conditions,
1,2
use of medications, or diet. Diet is recognized as a
determinative environmental factor that modulates the
3 secreted or attached to the bacterial cell wall and can affect
composition and metabolic activity of the GIT microbiota.
Consumption of specific dietary ingredients, such as dietary
fibers and prebiotics is an avenue by which the microbiome
can be modified substantially.
Dietary fibers are resistant to digestion and absorption in
the human small intestine, and are subjected to bacterial
fermentation in the GIT tract. Thus, dietary fibers may
influence microbial metabolic activities, including the
formation of fermentative end products, and they may modify
the composition of bacterial communities. Some dietary fibers
4
are classified as prebiotics, which are defined as
“nondigestible food ingredients that beneficially affect the
host by selectively stimulating the growth and/or activity of
one or a limited number of bacteria in the colon, and thus
5
improve host health”.
Most lactic acid bacteria (LAB) species are food-grade
organisms, which are generally recognized as safe (GRAS) for
human consumption. They are potentially capable of
synthesizing various classes of polysaccharides, e.g.
exopolysaccharides (EPS), which may play a role as
6,7
prebiotics. EPS are extracellular polysaccharides that are
adhesion by shielding cell surface adhesins or acting as
8
ligands. Due to claims of human health benefits, the EPS
produced by LAB are receiving a renewed interest from the
scientific community. It follows from the above that LAB-based
EPS have a great versatility for food and pharmaceutical
9,10
purposes.
In this paper, we examine current knowledge related to the
effects of dietary fibers and prebiotics on the GIT microbiome,
the prebiotic properties of EPS produced by LAB, and the
health-promoting benefits of these polymers (Fig. 1.).

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Figure 1 Dietary fibers, prebiotics, and exopolysaccharides (EPS) produced by
lactic acid bacteria: possible relationships and potential prebiotic properties
Dietary fibers and short-chain fatty acids
The term “dietary fiber” comprises a complex group of
substances with largely diverse chemical and morphological
structures, properties, and impacts. In general, dietary fibers
are primarily the storage and cell wall polysaccharides of
plants that cannot be digested by the endogenous enzymes of
the human digestive tract.11 Dietary fibers usually consist of
insoluble and soluble carbohydrates including cellulose, lignin,
and nonstarch polysaccharides such as hemicelluloses, pectins,
and arabinoxylan oligosaccharides.12 Other dietary fiber
components include nondigestible oligosaccharides, e.g. inulin
and oligofructose, as well as resistant starch, which is defined
as “the sum of starch and products of starch degradation not
absorbed in the small intestine of healthy individuals”.13,14
Dietary fibers demonstrate resistance to digestion in the
human small intestine, enabling passage in a largely intact
form into the colon where they increase viscosity and bulking
of the fecal matter.15 Dietary carbohydrates that escape
digestion undergo bacterial fermentation in the colon, thereby
affecting GIT microbial ecology and influencing gut
physiological processes.16
In diets, which contain few processed foods, much of the
dietary fibers are derived from the cell walls of plants and
plant products. These cell walls are all constructed similarly,
but vary considerably in their proportions and composition
depending on plant species and cell types. Pectins and
hemicelluloses as non-cellulosic polysaccharides also have a
variety of different structures.17
In the cell walls of most fruits and vegetables the matrix
polymers are mainly pectins, with smaller proportions of the
hemicellulose xyloglucan.18 By contrast, in the cell walls of
cereal grains hemicelluloses are predominant. The
hemicellulose arabinoxylan, which consists of β-1,4 linked
xyloses with branches of arabinose, predominates in wheat;
whereas 1,3;1,4-β-glucan, which is a linear polymer of β-
glucosyl units containing both 1,3- and 1,4-links and may
represent key determinants of wall plasticity and other
19
properties, usually predominates in oat and barley. In
addition, lignin present in the cell walls of food plants is also
included in the definition of dietary fiber. Lignin is not a
polysaccharide but an aromatic, hydrophobic polymer formed
by the coupling of hydroxycinnamyl alcohol monomers. It
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often crosslinks cell wall polysaccharides and inhibits their
20
enzymatic degradation.
Dietary intervention studies indicate that supplementation
with dietary fibers can beneficially alter the microbiota.
Although not degraded in the small intestine, dietary fiber
carbohydrates may be degraded in the colon by bacterial
enzymes, and the products thus formed are fermented by
bacteria to produce short-chain fatty acids (SCFAs), i.e.
acetate, propionate, and butyrate, and gases (carbon dioxide,
hydrogen, methane) and water. SCFAs are an important
indicator of bacterial fermentation in the colon, and serve as
Food & Function Accepted Manuscript
fuels in different tissues and may play a role in the regulation
of cellular processes.21
The concentration of SCFAs changes along the GIT tract
with the highest concentrations in the proximal colon and
declines progressively toward the distal colon, the region of
the GIT tract with the greatest density of microbes.22 SCFAs,
primarily butyrate, act as carbon and energy sources for
colonocytes, the endothelial cells of the large intestine, and
enterocytes, the epithelial cells of the small intestine.23,24
Propionate can also be utilized locally through conversion into
glucose by intestinal gluconeogenesis25 or diffuse into the
portal vein to be utilized as a substrate for hepatic
gluconeogenesis.22 Acetate is the most abundant SCFA found in
circulation, and has been shown to transport through the
blood–brain barrier.26,27
SCFAs also appear to influence the integrity of the GIT
epithelial barrier, glucose homeostasis, reduce inflammation
and regulate metabolism, energy balance, and appetite.28 They
have also been shown to reduce plasma concentrations of
cholesterol in rodents and humans through lowering
cholesterol synthesis rates.29 Moreover, there is a significant
correlation between SCFA levels and composition of the
microbiota because high SCFA concentrations in the gut lumen
lower the colonic pH (5.5–6.5 in the proximal colon where
fermentation is highest, compared to the distal colon with its
considerably higher pH levels of 6.5–7.0), thereby inhibiting
the growth of Gram-negative Enterobacteriaceae including
Salmonella spp. and Escherichia coli.30,31 Regarding allergic
diseases, the increased circulating levels of fiber-derived SCFAs
have been found to provide protection against inflammation in
the lung of mice. However, SCFA levels have been decreased
by a low-fiber diet, resulting in an increase in allergic airway
diseases (Fig. 2.).32
Figure 2 Bacterial production of short-chain fatty acids (SCFAs) and their functions
Overview of prebiotics
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The prebiotic effects of dietary oligosaccharides, i.e. inulin-
type fructans, fructooligosaccharides (FOS) and
galactooligosaccharides (GOS), have been extensively studied
33
in vivo. However, the categorization of fibers according to
their prebiotic properties requires further clarification, and
reliable methods to document whether a fiber is deemed a
prebiotic are still developing.
As was mentioned above, prebiotics have been defined as
“nondigestible but fermentable food ingredients that
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beneficially affect the host by selectively stimulating the
growth and/or activity of one or a limited number of bacteria
5
in the colon, and thus improve host health”. The following
three criteria are used to recognize a compound as prebiotic:
“(i) resistance to gastric acidity, to hydrolysis by mammalian
enzymes, and to GIT absorption, (ii) fermentation by intestinal
microflora, and (iii) selective stimulation of the growth and/or
activity of those intestinal bacteria that contribute to health
33
and well-being”. Prebiotics are metabolized by health-
promoting bacteria, primarily Bifidobacterium and/or
Lactobacillus spp., acting as carbon sources and improving host
34,35
immunity to fight against pathogenic organisms.
Oligosaccharides are the most commonly used prebiotic
34,36-38
food ingredients. Some prebiotics are low-digestible
carbohydrates and are associated with impaired GIT tolerance,
39,40
especially when consumed in large doses, whereas other
prebiotic fibers (e.g. wheat dextrin and polydextrose) show no
41
laxative effect up to 45 g/day.
Among prebiotics, inulin-type fructans have been most
extensively studied and have therefore acquired the status of
model prebiotics. Consumption of inulin-type fructans and
other prebiotics has been linked with significant health
benefits, including improvement of gut balance and transit,
enhancement in gut mucosal barrier integrity and function,
increased host mucosal immunity, increased SCFA production
and an associated reduction in mucosal interaction of
opportunistic enteric pathogens, and improvement in lipid
33,42
metabolism. Moreover, prebiotics have putative anti-
cancer properties by supporting the inhibition of the growth of
adenomas and carcinomas in the gut, and reducing the risk
43
factors involved in colorectal diseases, thus enhancing
44
gastrointestinal persistence and immune systems. In
addition, prebiotics have been shown to positively influence
mineral absorption, bone mineral content, and bone structure.
Even though dietary fibers and prebiotics are considered to
decrease mineral absorption, they actually increase the
45,46
absorption of calcium and magnesium. However, the
amount and type of prebiotics have a deep impact on the
composition and activity of the beneficial microbial
47
community.
Influence of dietary fibers on gastrointestinal
microbiome
With increasing recognition that gut microbiota plays an
essential role in health, interest has increased in methods of
modulating its composition and metabolic function. The
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capacity of diet to modify the GIT microbiota of humans and
other mammals has been thoroughly studied. The results
indicated that composition of the diet, habitual dietary
pattern, and acute dietary alteration all impact the microbial
48,49
communities within the gut. It was also shown that
significant changes in the levels of macronutrients and dietary
fibers, especially prebiotic dietary fibers, can rapidly induce
50
this mechanism.
Increasing evidence indicates that the bacteria residing
within the colon mucus layer strongly influence whether host
cellular homeostasis is reserved or inflammatory mechanisms
Food & Function Accepted Manuscript
are triggered. These effects may either occur through direct
interactions with host cells by immunomodulation or indirectly
17
with the production of bacterial metabolites, such as SCFAs.
Early studies of the effects of diet on the GIT microbiome
were typically performed using germ-free rodents inoculated
with fecal microbiota from human donors, which then
developed a microbiome similar to that of a mature human
51
adult. In a study by Kleessen et al., wherein germ-free rats
were inoculated with a human fecal flora and were fed on
different diets, bifidogenic effects (specific growth
enhancement of intestinal bifidobacteria) were observed in
the colon of rats fed oligofructose alone and in the caecum of
animals fed a diet supplemented with both oligofructose and
52
inulin. Compared with human flora-associated rats fed a
standard diet, these animals also exhibited higher caeco-
colonic numbers of lactobacilli (ܲ < 0.05) and significantly
reduced numbers of caecal, colonic, and fecal bacteria
52
belonging to possibly pathogenic clostridia.
Intervention studies in humans have shown that whole
53,54
grain and cereal fiber intakes increase microbiota diversity,
whereas low level of fiber consumption is purported to be a
driver in the depletion of the human GIT microbiota and later
increases in chronic diseases, such as obesity, type 2 diabetes,
3,11,55,56
cardiovascular disease, and colon cancer. Similarly,
cross-sectional studies of human populations have revealed an
association between greater dietary fiber intakes and
57
increased GIT microbial diversity. Definite shifts in bacterial
diversity and generation of fecal fermentation end products
have been demonstrated in humans 24 h after switching from
a diet rich in fiber (> 30 g/day) to a meat-based diet essentially
58
devoid of fiber.
Additionally, even though the results are not conclusive,
the administration of nondigestible dietary fibers appears to
have promising effects (i.e. prevention or alleviation of
antibiotic-associated diarrhea) on the GIT microbiome during
59
antibiotic treatment.
It is important to note that the various types of dietary
fibers have different properties and may have different effects
on health, especially in inflammatory bowel diseases (IBD), e.g.
60
Crohn’s disease and ulcerative colitis. Wong et al. have
proposed that, based on the results of clinical trials involving
the use of specific dietary fibers, it may be assessed whether
the consumption of a particular kind of dietary fiber offers a
17
potentially efficient treatment for an IBD patient.
In summary, there is a large number of putative
advantageous effects attributed to consumption of dietary
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fibers and prebiotics, which are primarily due to the selective against antimicrobial factors such as bacteriophages,
65,71
stimulation of the intestinal microbiota. These physiological phagocytosis, or predation by protozoa.
processes have been directed mainly toward the colon and These high molecular weight polymers with diverse
may also have local and systemic health benefits. However, in physicochemical properties have shown a multitude of
considering the effects it has to be taken into account that the beneficial health effects in a variety of commercial
consumed diet probably contains different types of fibers and applications. Thus, microbial EPS are widely exploited
prebiotics at different doses. industrially, especially in food and cosmetic products,
agronomy, pharmaceutical industries, and medical
6,72
products. LAB-based fermented foods, due in part to their
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Exopolysaccharides produced by lactic acid EPS content, display a high level of hygienic safety, storage
73,74
bacteria stability, and attractive sensory properties.

Food & Function Accepted Manuscript

From a technological perspective, EPS-producing LAB may
A wide range of bacteria are surrounded by carbohydrate
greatly contribute to the texture, rheology, and mouthfeel of
polymers termed as exopolysaccharides (EPS). Thus, certain
cultured dairy foods. Because of their pseudo-plastic
LAB strains belonging to Lactococcus, Leuconostoc,
rheological behavior and water-binding capacity, microbial EPS
Lactobacillus, Pediococcus, Weissella, and Streptococcus spp.
have found industrial applications as texturizing, viscosifying,
are capable of producing a variety of EPS and then export 75,76
emulsifying, and syneresis-lowering agents. The rheological
them into the extracellular environment, e.g. milk.61,62 It must
and textural properties of EPS depend on their chemical
also be noted that most LAB are able to produce EPS, 77,78
composition and structural characteristics.
but―despite the many listed species―over-production is not
Currently, EPS are widely used in the manufacture of
common. Moreover, the molecular characteristics of EPS and
fermented dairy products such as conventional yogurt,
their effects on microbial functions or host health can be diverse
drinking yoghurt, milk-based desserts, cheese, and other types
between species and strains.63 62,79-81
of fermented milks.
EPS from LAB are high molecular weight sugar polymers
There is an ever increasing consumer demand for low- or
encompassing two groups, i.e. homopolysaccharides (HoPS)
reduced-fat, low-sugar, and low-calorie foods containing no or
and heteropolysaccharides (HePS).64 HoPS are synthesized by
largely reduced levels of additives. LAB-based EPS as
extracellular or cell wall-anchored glycansucrases that use
biothickeners offer a natural alternative to commercial food
sucrose as substrate and are composed of a single type of
additives without negatively affecting the textural attributes of
monosaccharide, either glucose (α-D-glucans) or fructose (β-D- 73,80,82,83
the final products. As has already been mentioned,
fructans). HePS are polymers of a repeating unit (an
these extracellular polysaccharides are particularly important
oligosaccharide containing 3–8 monosaccharides) that is
in fermented dairy products; however, a few studies have
synthesized out of sugar nucleotide precursors and
investigated EPS for application in the cereal and bakery
polymerized extracellularly.6,61 However, variations in sugar 84
industries, and mainly in gluten-free products.
composition, chain length, degree of branching, and sugar
There is an immune-mediated disorder called coeliac
linkages in EPS produced by different LAB have been observed
disease, which is triggered by gluten exposure, and its only
as leading factors determining the rheological and health-
effective treatment is lifelong adherence to a gluten-free
promoting potential of EPS.65 85
diet. The global prevalence of coeliac disease is about 1–2%,
As far as phenotype is concerned, two groups of EPS- 86
and it appears to be increasing. However, gluten
producing LAB strains are often distinguished as follows: (i)
replacement in gluten-free bakery products is a technological
“ropy” phenotypes form long filaments when touched with an
challenge, because it has unique viscoelastic properties, such
inoculation loop and then slowly withdrawn and (ii) “mucoid”
as roles in water holding capacity of the dough and in gas
or “non-ropy” phenotype strains appear as glistening, smooth 87
retention during fermentation.
colonies growing on suitable agar plates and are unable to
Several studies have shown the potential of LAB-based EPS
produce strands.66,67
both for enhancing the quality of gluten-free bakery products,
The physiological roles of EPS in microbe–host interactions
thereby offering an alternative to commercially employed
are not yet completely understood and are largely strain- 88
hydrocolloids , and for improving wheat sourdough bread
dependent.63 They are not used as energy sources by the 89
qualities. It should be noted that individuals who have
producer microorganism but are involved in the protection of
coeliac disease and, therefore, require a gluten-free diet may
microbial cell integrity in an ecosystem against harsh 90
also suffer from lactose intolerance or milk protein allergy. In
conditions, i.e. dehydration, osmotic stress, pathogenic
their case, the use of milk or milk powders to stimulate EPS
microbes, and in the colonization of natural habitats by the
production by LAB during sourdough making must be avoided.
EPS-producing bacteria.61,65,68
In situ EPS production by LAB is a better approach than
EPS may physically protect cell walls from toxic compounds
supplementation with food additives, including the addition of
(e.g. metal ions or ethanol), nisin, lysozyme, cleaning agents,
EPS as bioingredients, to improve rheological characteristics of
and antibiotics.69,70 Furthermore, they are thought to play a 91
yogurts. Moreover, the EPS produced in situ need not be
role in cellular recognition, biofilm formation, quorum-sensing
indicated in the list of ingredients on the product label. The
control, exchange of genetic information, and protection
application of LAB-derived EPS can be economically feasible if

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production parameters are optimized, i.e. inexpensive
substrates and cost-effective fermentation conditions are
79,92,93
used.
Finally, it is worth mentioning that the effects of EPS on the
physiological properties of dough, breads, or dairy products
mainly depend on their monosaccharide composition,
94
molecular mass, linkages, and degree of branching.
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Prebiotic properties of exopolysaccharides
Although dietary fibers and prebiotics are usually of plant
origin, there is growing evidence that microbial EPS have
analogue structures that can potentially exert similar
93,95-97
physiological effects.
There are varying reports in the literature on the abilities of
EPS to show resistance to biodegradation when passing
through the human GIT tract. Some EPS have been found to be
readily degraded, whereas others retain integrity during
98
gastric transit. As the structural complexity of extracellular
polymers varies, biodegradability and prebiotic properties can
6,65,99
also differ greatly. Nevertheless, once the EPS reach the
colonic lumen, they must have the ability to selectively
stimulate the growth of colonic bacteria species, which will in
turn exert a beneficial effect on the host.
Hongpattarakere et al. reported that EPS isolated from a
Lactobacillus plantarum strain exhibited considerable prebiotic
potential by showing a high resistance to simulated gastric and
intestinal digestion and a selective enhancement of beneficial
100
gut bacteria, particularly bifidobacteria. EPS from Lb.
plantarum showed low digestibility by artificial gastric juice
and also displayed in vitro prebiotic activities in another study.
These polymers increased the growth of probiotic
Bifidobacterium infantis and Lb. acidophilus; however, did not
101
support the growth of non-probiotic Enterobacteriaceae. In
another experiment by Tsuda and Miyamoto, the EPS
produced by a mutant Lb. plantarum strain achieved higher
prebiotic scores for seven out of eight LAB strains in
102
comparison with GOS and inulin.
Dal Bello et al. studied the prebiotic properties of levan-
type EPS from Lb. sanfranciscensis and confirmed the
103
bifidogenic effect. Baruah et al. reported that EPS from
Weissella cibaria showed significantly reduced digestibility
compared to commercial inulin, and its fermentability by
probiotic intestinal microbiota proved its effectiveness as an
104
efficient soluble prebiotic.
According to Russo et al., the EPS produced by Pediococcus
parvulus may positively modulate the growth of probiotic
105
microorganisms. In contrast, Lindström et al. reported that
purified EPS from Pc. parvulus failed to elicit prebiotic effects
in a mouse model, although consumption of viable EPS-
producing bacteria antagonized Enterobacteriaceae without
93
disturbing the homeostasis of the microbiota.
The aforementioned findings suggest that LAB-produced
EPS, which are resistant to the harsh conditions of the human
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GIT system, are potentially capable of positively influencing
35,64,99,106
the probiotic microbiota of the host organism.
However, no human intervention trials have been carried out
to demonstrate the prebiotic properties of these bacterial
biopolymers and, therefore, it requires further investigations
to confirm or refute the capability of bacterial EPS to act as
modulators of the beneficial colonic microbiota and to
associate this modulation with a healthy effect for the host.
Health-promoting benefits of exopolysaccharides
Food & Function Accepted Manuscript
In addition to their ecological functions and technological
usefulness, the EPS produced by LAB have been claimed to
exert health benefits. Through their prebiotic properties, LAB-
based EPS may confer cardioprotective effects and control the
98,106
abnormalities occurring in metabolic syndrome. The
potential role of EPS in cholesterol lowering will be detailed in
a separate chapter.
Furthermore, EPS may induce positive physiological
9,107 108-110
responses including antiulcer and antioxidant effects.
Rodríguez et al. demonstrated that the purified EPS from
Streptococcus thermophilus CRL 1190 was capable of
111
preventing chronic gastritis.
LAB-derived EPS were reported to play an important role
112,113
as anti-inflammatory and antitumor agents. They may
also enhance immunological functions such as proliferation of
T-lymphocytes, activation of macrophages, induction of
cytokines (interferon-g, interleukin-1,a), and may have the
capacity to modify some macrophage and splenocyte
114
functions. The study of de Paiva et al. suggested that the
purified α-glucan-type EPS of Lb. kefiranofaciens and Lb.
satsumensis had significant effects on the intestinal IgA-
producing cells; however, they did not influence the
expression of proinflammatory and regulatory cytokines in the
115
intestine of mice. Matsuzaki et al. demonstrated that
Leuconostoc mesenteroides NTM048 was capable of secreting
116
EPS that showed high IgA-inducing ability.
Many LAB EPS have the potential to exert beneficial effects
on the innate and adaptive immunity of the intestine.
Therefore, these could be exploited as biopolymers to help
reduce intestinal inflammation associated with chronic
117
diseases and reduce colitis. EPS were also reported to
positively influence the passage of LAB through the intestine
99,118,119
and aid in LAB colonization of the gut. Depending on
type and dose, EPS can modulate LAB’s efficiency of adhesion
120
to intestinal epithelial cells in vitro.
Despite the previously outlined benefits (Fig. 3.), no health
claims on LAB EPS have so far been approved by either the
European Food Safety Authority or the US Food and Drug
Administration. The safety and health-promoting efficacy of
EPS need to be demonstrated in human clinical trials to obtain
legal approval.
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Figure 3 Beneficial effects of lactic acid bacteria (LAB)-based exopolysaccharides
(EPS) on human health
Cholesterol-lowering effect of dietary fibers and
prebiotics
The risk of heart attack is three times higher in individuals with
hypercholesterolemia compared to those who have normal
blood lipid profiles. The American Heart Association has
predicted that 40.5% of the US population would have some
form of cardiovascular disease (CVD) by 2030, and this disease
will remain the leading cause of death, affecting approximately
121,122
23.6 million people globally. It was proved that even 1%
reduction in serum low-density lipoprotein (LDL) cholesterol
decreases the risk of coronary heart disease by up to 3% over a
123
lifetime. Furthermore, hypercholesterolemia is a risk factor
of type 2 diabetes mellitus and metabolic syndrome.
124
The cholesterol-lowering effect of probiotics has been
extensively documented, and prebiotics have also gained
increased attention in cholesterol studies. Epidemiological
researches suggest that adequate dietary fiber intake
consistently reduces the risk of CVD, mainly through a
4
reduction in cholesterol levels. As for dietary fiber types, the
majority of studies have been done with FOS, GOS, inulin, and
oligofructose. Various in vivo randomized, double-blind,
placebo-controlled and crossover trials were designed to prove
the administration of these polysaccharides to be effective in
improving lipid profiles, including reductions in serum or
plasma total cholesterol, LDL cholesterol, and total
triglycerides, or an increase in high-density lipoprotein (HDL)
cholesterol.
106
In a study using hypercholesterolemic subjects to assess
the effects of inulin on blood cholesterol level, it was found
that a daily consumption of 20 g of inulin for a 3-week period
125
significantly reduced (ܲ < 0.05) serum triglycerides.
Similarly, a daily intake of 10 g of inulin resulted in a significant
decrease (ܲ < 0.05) in plasma triglyceride levels compared to
126
the placebo treatment. Moreover, Brighenti et al. found that
9 g/day of inulin significantly reduced (ܲ < 0.05) plasma total
cholesterol and triglycerides by 7.9% (± 5.4) and 21.2% (± 7.8),
respectively, compared to control in a randomized, double-
blind, placebo-controlled and parallel design trial wherein
127
twelve healthy men were involved.
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Food & Function
Fructan was also reported to significantly reduce blood
cholesterol by 29.7% (ܲ < 0.001), LDL cholesterol
concentration by 25.8% (ܲ < 0.01), intermediate-density
lipoprotein (IDL) cholesterol level by 39.4% (ܲ < 0.001), and
very-low-density lipoprotein (VLDL) cholesterol concentration
by 37.3% (ܲ < 0.05). In this 16-week-long study, male mice
were fed a purified diet which contained 10% of long-chain
128
fructan.
Other indigestible and fermentable compounds (e.g.
oligodextrans and resistant starch) were also found to exert
hypocholesterolemic effects. In a randomized, placebo-
Food & Function Accepted Manuscript
controlled and parallel designed experiment, 10 g of resistant
starch was fed to male guinea pigs for 4 weeks. The results
indicated that the resistant starch tested significantly reduced
(ܲ < 0.01) plasma cholesterol by 27.3% and LDL cholesterol by
28.0%.129 Hypercholesterolemic male rats fed on starch for 8
weeks were reported to have significantly decreased (ܲ < 0.05)
plasma total cholesterol, LDL cholesterol and triglyceride
levels.130
Guo et al. conducted a randomized, placebo-controlled
study involving rats which were fed experimental diets
containing 10% of oat flour for 30 days.131 Significantly reduced
plasma total cholesterol concentrations were observed.
Dietary oat improved hypercholesterolemia by enhancing the
excretion of fecal bile acids. It should be noted, however, that
these improvements were not only related to the presence of
β-glucan, but also to that of lipids and proteins.131
The ability of soluble dietary fibers to lower plasma
cholesterol levels appears to be due to three different
biological mechanisms as follows132 (Fig. 4.):
i) Prevention of bile salt reabsorption from the small
intestine into the enterohepatic circulation, leading to an
excess bile salt excretion in feces. This process causes a
depletion of bile salts in the liver and, consequently,
cholesterol is rapidly catabolized in the hepatocytes to
replenish the bile salt pool.133
It is known that liver hepatocytes produce bile salts which
promote dietary lipid and cholesterol absorption as well as
transport throughout the intestinal epithelium. The synthesis
of bile salts de novo involves the formation of primary bile
acids from cholesterol and conjugation with glycine (to form
glycocholic acid) or taurine (to form taurocholic acid) in the
liver. More than 95% of bile salts are reabsorbed by the
enterohepatic circulation to the liver,134 and are taken up by
hepatocytes, reconjugated and resecreted, into bile. Because
most bile acids are reabsorbed, there is no need to de novo
synthesis from cholesterol, and it can lead to the accumulation
of cholesterol in the host body. However, several dietary fibers
and prebiotics are capable of interacting with bile acids in the
small intestine, resulting in an increase in the fecal loss of free
bile acids. This may stimulate the liver to synthesize new bile
salts from the available cholesterol, which obviously reduces
hepatic free cholesterol levels.135
ii) Increased SCFA production in the caecum and colon,
due to microbial fermentation of soluble fibers, can alter
hepatic lipogenesis and significantly promote fecal excretion of
136,137
bile acids.
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Bacterial fermentation of fibers generates SCFAs, which are
associated with a range of beneficial health outcomes, as was
mentioned above, including hypolipidemic effects. All four
common SCFAs can decrease plasma cholesterol levels, but
propionate has been suggested to directly inhibit hepatic
cholesterol synthesis, whereas acetate stimulates
136-138
lipogenesis. Moreover, propionate is an inhibitory
molecule that might use acetate as a precursor for the
139-141
transport into hepatocytes.
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iii) Reduced glycemic response by delayed absorption of
macronutrients, resulting in an increased insulin sensitivity
and a lowered insulin stimulation of hepatic cholesterol
synthesis. Because insulin is capable of activating HMG-
CoA reductase, which promotes hepatic cholesterol
synthesis, a decline in insulin level inhibits this enzyme,
leading to a drop in hepatic cholesterol synthesis rates.142-
144
Butyrate may also inhibit HMG-CoA reductase activity,
thus preventing cholesterol absorption.145
Figure 4 Possible biological pathways linked to hypocholesterolemic effects of
prebiotics on host health
However, some studies have raised controversies about
the hypocholesterolemic properties of prebiotics. In a
randomized, placebo-controlled, double-blind, and crossover
study, diets containing inulin and wheat fiber at 3–4 g/100 g
were given to eight volunteers but the results showed no
significant changes in their lipid profiles.146 In another
randomized, placebo-controlled, double-blind, and crossover
study, 10 diabetic patients (6 men, 4 women) received 20
g/day of FOS for 4 weeks; however, FOS had no effect on their
plasma glucose and insulin concentrations, basal hepatic
glucose production, and lipid profiles.147
Although in vivo experiments utilize real-life models with
true representation of the biological and pathological systems,
these studies are also easily affected by external factors, such
as different types of prebiotics, inaccurate administration
dosage or clinical characteristics of subjects, short treatment
duration, unequal sample sizes, lack of suitable controls or
placebo groups, or even analytical inaccuracy of lipid analyses.
Even though many trials were performed, the results are at
times contradictory and, therefore, prebiotics
supplementation and its relationship with blood lipid levels
warrant further research.
Potential cholesterol-lowering effect of
exopolysaccharides
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DOI: 10.1039/C8FO00118A
REVIEW
Some EPS, mainly HoPS, have structures, chemical
composition, and linkage types similar to those of dietary
fibers, especially inulin and FOS, which are the best studied
prebiotics. The most noticeable difference among these
molecules is their size and degree of polymerization. FOS and
inulin are short oligosaccharides with an estimated molecular
weight of 5 kDa, whereas HoPS are branched polymers of high
35
molecular weight, approximately 1000 kDa.
Several studies indicated the beneficial effects of EPS on
modulation of the gut microbiota. They can increase the
caecum contents, demonstrating a bulking effect commonly
Food & Function Accepted Manuscript
148
seen with prebiotics. Because LAB-based EPS appear to
behave like prebiotics, they can also reduce the potential risks
associated with elevated plasma lipid levels, thus showing
promise in CVD prevention.149 For example, the EPS produced
by Lb. kefiranofaciens, kefiran, was reported to reduce serum
cholesterol levels and suppress the increase in blood pressure
in rats consuming excessive amounts of cholesterol.150
London et al. demonstrated the potential of EPS-producing
Lactobacillus strains in hypocholesterolemic therapies. The
EPS-producing lactobacilli were found to have a positive effect
on lipid metabolism by decreasing serum triglycerides, total
serum and liver cholesterol in mice fed a high-fat, high-
cholesterol diet.151
The study of Ghoneim et al. has suggested that EPS from
Bacillus subtilis sp. suppress improves dyslipidemia,
hyperglycemia, and cardiovascular disease risk in diabetic rats.
The isolated polymer was shown to reduce total serum
cholesterol, LDL, VLDL, and triglycerides, whereas it proved to
elevate HDL. The polysaccharide also decreased atherogenic
and coronary risk indices, as confirmed by histopathology.110
Tok and Aslim reported that out of five Lb. delbrueckii
subsp. bulgaricus strains three were capable of producing high
amounts of EPS, and these removed more cholesterol from the
growth medium than did the low EPS-producing strains.
Immobilized cells were much more effective in cholesterol
removal than free cells.152
EPS from both Lb. plantarum BR2153 and Enterococcus
faecium K1154 were reported to lower cholesterol
concentrations by approximately 50% in in vitro assays as
compared to control media. In contrast, Lindström et al. stated
that EPS excreted by Pc. parvulus 2.6 had no effect on plasma
cholesterol and triglyceride levels of mice on the experimental
diets compared to the control group.93
Furthermore, although kefiran produced by Lb.
kefiranofaciens was shown to prevent the development of
atherosclerosis in hypercholesterolemic rabbits, through anti-
inflammatory and antioxidant actions, it caused no significant
difference in cholesterol or triglyceride levels of serum and
lipoprotein fractions between the two groups tested, i.e. male
rabbits fed a 0.5% cholesterol diet with or without kefiran for 8
weeks.155
All things considered, many experimental studies have
demonstrated that EPS produced by LAB strains may lower
blood cholesterol level and potentially offer a natural
alternative for the treatment of hypercholesterolemia;
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REVIEW
however, the results are at times contradictory. The exact
mechanism of cholesterol lowering is not completely
understood, and it is important to note that although
convincing lipid-lowering effects have been observed in
animals, few such reports exist for humans.
Conclusions
The human microbiome contributes fundamental
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functionalities to human physiology and is considered essential
for the maintenance of health. Consumption of specific dietary
ingredients, such as dietary fibers and prebiotics, is a potential
way by which the microbiota can be modulated and even a
reduction in serum cholesterol levels may thus be expected.
Numerous LAB species have the ability to synthesize
polysaccharides, especially EPS, which are used as functional
ingredients in various food products. EPS have the prebiotic
potential to positively affect the GIT microbiome and
presumably reduce cholesterol, which is a promising avenue
for future investigations because currently only limited data
are available from in vivo studies in humans and animal
models and from in vitro trials. However, as dietary fibers
comprise a complex group of substances with very diverse
structures, properties, and impacts, EPS also differ greatly and
show a multitude of beneficial health effects. Therefore,
further experiments are clearly needed in this area. Moreover,
the efficacy of LAB-based EPS should be demonstrated through
well-designed, double-blind, placebo-controlled human clinical
trials to obtain legal approval from relevant authorities.
Conflicts of interest
There are no conflicts to declare.
Acknowledgments
This work was financially supported by the ÚNKP-17-3 New
National Excellence Program of the Ministry of Human
Capacities, Hungary.
References
1 R. Jumpertz, D. S. Le, P. J. Turnbaugh, C. Trinidad, C.
Bogardus, J. I. Gordon and J. Krakoff, Am. J. Clin. Nutr., 2011,
94, 58–65.
2 J. R. Goldsmith and R. B. Sartor, J. Gastroenterol., 2014, 49,
785–798.
3 J. L. Sonnenburg and F. Bäckhed, Nature, 2016, 535, 56–64.
4 J. Slavin, Nutrients, 2013, 5, 1417–1435.
5 G. R. Gibson and M. B. Roberfroid, J. Nutr., 1995, 125, 1401–
1412.
6 V. K. Bajpai, I. A. Rather, R. Majumder, S. Shukla, A. Aeron, K.
Kim, S. C. Kang, R. C. Dubey, D. K. Maheshwari, J. Lim and Y.
H. Park, Bangladesh J. Pharmacol., 2016, 11, 1–23.
7 V. Vendramin, L. Treu, S. Campanaro, A. Lombardi, V. Corich
and A. Giacomini, Food Microbiol., 2017, 63, 47–57.
8 A. M. Barnett, N. C. Roy, W. C. McNabb and A. L. Cookson,
Food Funct., 2012, 3, 690–699.
8 | Food Funct, 2018, 00, 1-10
Please do not adjust margins
Page 8 of 11
View Article Online
DOI: 10.1039/C8FO00118A
Food & Function
9 S. Badel, T. Bernardi and P. Michaud, Biotechnol. Adv., 2011,
29, 54–66.
10 P. S. Botelho, M. I. S. Maciel, L. A. Bueno, M. F. F. Marques,
D. N. Marques and T. M. Sarmento Silva, Carbohydr. Polym.,
2014, 107, 1–6.
11 H. D. Holscher, Gut Microbes, 2017, 8, 172–184.
12 S. C. Fry, New Phytol., 2004, 161, 641–675.
13 H. N. Englyst, S. M. Kingman and J. H. Cummings, Eur. J. Clin.
Nutr., 1992, 46, S33–S50.
14 C. Chassard and C. Lacroix, Curr. Opin. Clin. Nutr. Metab.
Care, 2013, 16, 453–460.
15 J. M. Lattimer and M. D. Haub, Nutrients, 2010, 2, 1266–
1289.
Food & Function Accepted Manuscript
16 M. A. J. Hullar, A. N. Burnett-Hartman and J. W. Lampe,
Cancer Treat. Res., 2014, 159, 377–399.
17 C. Wong, P. J. Harris and L. R. Ferguson, Int. J. Mol. Sci., 2016,
17, 919.
18 M. M. L. Grundy, C. H. Edwards, A. R. Mackie, M. J. Gidley, P.
J. Butterworth and P. R. Ellis, Br. J. Nutr., 2016, 116, 816-833.
19 R. A. Burton and G. B. Fincher, Front. Plant Sci., 2014, 5, 456.
20 Z. Merali, S. R. A. Collins, A. Elliston, D. R. Wilson, A. Käsper
and K. W. Waldron, Biotechnol. Biofuels, 2015, 8, 23.
21 H. L. Simpson and B. J. Campbell, Aliment. Pharmacol. Ther.,
2015, 42, 158–179.
22 J. H. Cummings, E. W. Pomare, W. J. Branch, C. P. E. Naylor
and G. T. Macfarlane, Gut, 1987, 28, 1221–1227.
23 H. J. Flint, E. A. Bayer, M. T. Rincon, R. Lamed and B. A.
White, Nat. Rev. Microbiol., 2008, 6, 121–131.
24 H. M. Hamer, D. Jonkers, K. Venema, S. Vanhoutvin, F. J.
Troost and R. J. Brummer, Aliment. Pharmacol. Ther., 2008,
27, 104–119.
25 F. De Vadder, P. Kovatcheva-Datchary, D. Goncalves, J.
Vinera, C. Zitoun, A. Duchampt, F. Bäckhed and G. Mithieux,
Cell, 2014, 156, 84–96.
26 G. Frost, M. L. Sleeth, M. Sahuri-Arisoylu, B. Lizarbe, S.
Cerdan, L. Brody, J. Anastasovska, S. Ghourab, M. Hankir, S.
Zhang, D. Carling, J. R. Swann, G. Gibson, A. Viardot, D.
Morrison, E. L. Thomas and J. D. Bell, Nat. Commun., 2014, 5,
3611.
27 R. J. Perry, L. Peng, N. A. Barry, G. W. Cline, D. Zhang, R. L.
Cardone, K. F. Petersen, R. G. Kibbey, A. L. Goodman and G. I.
Shulman, Nature, 2016, 534, 213–217.
28 A. Koh, F. De Vadder, P. Kovatcheva-Datchary and F.
Bäckhed, Cell, 2016, 165, 1332–1345.
29 T. Fushimi, K. Suruga, Y. Oshima, M. Fukiharu, Y. Tsukamoto
and T. Goda, Br. J. Nutr., 2006, 95, 916–924.
30 K. P. Scott, S. H. Duncan and H. J. Flint, Nutr. Bull., 2008, 33,
201–211.
31 S. H. Duncan, P. Louis, J. M. Thomson and H. J. Flint, Environ.
Microbiol., 2009, 11, 2112–2122.
32 A. Trompette, E. S. Gollwitzer, K. Yadava, A. K. Sichelstiel, N.
Sprenger, C. Ngom-Bru, C. Blanchard, T. Junt, L. P. Nicod, N.
L. Harris and B. J. Marsland, Nat. Med., 2014, 20, 159–166.
33 M. Roberfroid, J. Nutr ., 2007, 137, 830S–837S.
34 S. Macfarlane, G. T. Macfarlane and J. H. Cummings, Aliment.
Pharmacol. Ther., 2006, 24, 701–714.
35 N. Salazar, M. Gueimonde, C. G. de Los Reyes-Gavilán and P.
Ruas-Madiedo, Crit. Rev. Food Sci. Nutr., 2016, 56, 1440–
1453.
36 L. Varga, J. Szigeti and É. Csengeri, Milchwissenschaft, 2003,
58, 55–58.
37 L. De Vuyst, L. Avonts and E. Makras, in Functional Foods,
Ageing and Degenerative Disease, eds. C. Remacle and B.
Reusens, Woodhead Publishing Ltd., Cambridge, United
Kingdom, 2004, 17, 416–482.
38 L. Varga, J. Szigeti and B. Gyenis, Ann. Microbiol., 2006, 56,
139–141.
This journal is © The Royal Society of Chemistry 2018
 Page 9 of 11 PleaseFood & Function
do not adjust margins
Food & Function
39 G. A. Lied, K. Lillestøl, R. Lind, J. Valeur, M. H. Morken, K.
Vaali, K. Gregersen, E. Florvaag, T. Tangen and A. Berstad,
Scand. J. Gastroenterol., 2011, 46, 1169–1178.
40 H. A. Grabitske and J. L. Slavin, Crit. Rev. Food Sci. Nutr.,
2009, 49, 327–360.
41 W. Pasman, D. Wils, M. H. Saniez and A. Kardinaal, Eur. J.
Clin. Nutr ., 2006, 60, 1024–1034.
42 D. Bosscher, J. Van Loo and A. Franck, Nutr. Res. Rev., 2006,
19, 216–226.
43 M. T. Liong, Int. J. Mol. Sci., 2008, 9, 854–863.
44 H. Hardy, J. Harris, E. Lyon, J. Beal and A. D. Foey, Nutrients,
Published on 18 May 2018. Downloaded by Kaohsiung Medical University on 18/05/2018 14:39:35.
2013, 5, 1869–1912.
45 K. E. Scholz-Ahrens, P. Ade, B. Marten, P. Weber, W. Timm,
Y. Açil, C. C. Glüer and J. Schrezenmeir, J. Nutr ., 2007, 137,
838S–846S.
46 S. H. Al-Sheraji, A. Ismail, M. Y. Manap, S. Mustafa, R. M.
Yusof and F. A. Hassan, J. Func. Food, 2013, 5, 1542–1553.
47 H. J. Flint, Nutr. Rev., 2012, 70, S10–S13.
48 B. D. Muegge, J. Kuczynski, D. Knights, J. C. Clemente, A.
González, L. Fontana, B. Henrissat, R. Knight and J. I. Gordon,
Science, 2011, 332, 970–974.
49 S. Kuo, Adv. Nutr., 2013, 4, 16–28.
50 G. D. Wu, J. Chen, C. Hoffmann, K. Bittinger, Y. Y. Chen, S. A.
Keilbaugh, M. Bewtra, D. Knights, W. A. Walters, R. Knight, R.
Sinha, E. Gilroy, K. Gupta, R. Baldassano, L. Nessel, H. Li, F. D.
Bushman and J. D. Lewis, Science, 2011, 334, 105–108.
51 P. Van den Abbeele, P. Gérard, S. Rabot, A. Bruneau, S. El
Aidy, M. Derrien, M. Kleerebezem, E. G. Zoetendal, H. Smidt,
W. Verstraete, T. Van de Wiele and S. Possemiers, Environ.
Microbiol., 2011, 13, 2667–2680.
52 B. Kleessen, L. Hartmann and M. Blaut, Br. J. Nutr ., 2001, 86,
291–300.
53 I. Martínez, J. M. Lattimer, K. L. Hubach, J. A. Case, J. Yang, C.
G. Weber, J. A. Louk, D. J. Rose, G. Kyureghian, D. A.
Peterson, M. D. Haub and J. Walter, ISME J., 2013, 7, 269–
280.
54 J. Tap, J. P. Furet, M. Bensaada, C. Philippe, H. Roth, S. Rabot,
O. Lakhdari, V. Lombard, B. Henrissat, G. Corthier, E.
Fontaine, J. Doré and M. Leclerc, Environ. Microbiol., 2015,
17, 4954–4964.
55 K. Y. Hur and M. S. Lee, Diabetes Metab. J., 2015, 39, 198–
203.
56 E. C. Deehan and J. Walter, Trends Endocrinol. Metab., 2016,
27, 239–242.
57 N. Segata, Curr. Biol., 2015, 25, R611–R613.
58 L. A. David, C. F. Maurice, R. N. Carmody, D. B. Gootenberg, J.
E. Button, B. E. Wolfe, A. V. Ling, A. S. Devlin, Y. Varma, M. A.
Fischbach, S. B. Biddinger, R. J. Dutton and P. J. Turnbaugh,
Nature, 2014, 505, 559–563.
59 J. H. Moore, C. C. D. Pinheiro, E. I. Zaenker, D. T. Bolick, G. L.
Kolling, E. van Opstal, F. J. D. Noronha, P. H. Q. S. De
Medeiros, R. S. Rodriguez, A. A. Lima, R. L. Guerrant and C. A.
Warren, PLoS One, 2015, 10, e.0131829.
60 J. Barouei, Z. Bendiks, A. Martinic, D. Mishchuk, D. Heeney, Y.
H. Hsieh, D. Kieffer, J. Zaragoza, R. Martin, C. Slupsky and M.
L. Marco, Mol. Nutr. Food Res., 2017, 61, 1700184. DOI:
10.1002/mnfr.201700184.
61 L. De Vuyst and B. Degeest, FEMS Microbiol. Rev., 1999, 23,
153–177.
62 P. V. Behare, R. Singh, M. Kumar, J. B. Prajapati and R. P.
Singh, J. Food Sci. Technol., 2009, 46, 1–11.
63 I.-C. Lee, G. Caggianiello, I. I. van Swam, N. Taverne, M.
Meijerink, P. A. Bron, G. Spano and M. Kleerebezem, Appl.
Environ. Microbiol., 2016, 82, 3959–3970.
64 R. Baruah, D. Das and A. Goyal, J. Prob. Health, 2016, 4, 141.
DOI: 10.4172/2329-8901.1000141.
65 P. Ruas-Madiedo, J. Hugenholtz and P. Zoon, Int. Dairy J.,
2002, 12, 163–171.
This journal is © The Royal Society of Chemistry 2018
Please do not adjust margins
View Article Online
DOI: 10.1039/C8FO00118A
REVIEW
66 B. Rühmann, J. Schmid and V. Sieber, Front. Microbiol., 2015,
6, 565.
67 S. Mende, H. Rohm and D. Jaros, Int. Dairy J., 2016, 52, 57–
71.
68 F. Donot, A. Fontana, J. C. Baccou and S. Schorr-Galindo,
Carbohydr. Polym., 2012, 87, 951–962.
69 P. J. Looijesteijn, L. Trapet, E. de Vries, T. Abee and J.
Hugenholtz, Int. J. Food Microbiol., 2001, 64, 71–80.
70 E. Zannini, D. M. Waters, A. Coffey and E. K. Arendt, Appl.
Microbiol. Biotechnol., 2016, 100, 1121–1135.
71 H. C. Flemming and J. Wingender, Nat. Rev. Microbiol., 2010,
8, 623–633.
72 U. Surayot, J. Wang, P. Seesuriyachan, A. Kuntiya, M.
Food & Function Accepted Manuscript
Tabarsa, Y. Lee, J. K. Kim, W. Park and S. You, Int. J. Biol.
Macromol., 2014, 68, 233–240.
73 F. Freitas, V. D. Alves and M. A. M. Reis, Trends Biotechnol.,
2011, 29, 388–398.
74 I. A. Rather, B. J. Seo, V. J. R. Kumar, U. H. Choi, K. H. Choi, J.
Lim and Y. H. Park, Food Sci. Biotechnol., 2014, 23, 195–200.
75 N. Canquil, M. Villarroel, S. Bravo, M. Rubilar and C. Shene,
Carbohydr. Polym., 2007, 68, 270–279.
76 V. P. Kodali, S. Das and R. Sen, Food Res. Int., 2009, 42, 695–
699.
77 M. C. Gentès, S. L. Turgeon and D. St-Gelais, Int. Dairy J.,
2016, 55, 79–86.
78 L. Zhang, D. M. Folkenberg, J. M. Amigo and R. Ipsen, Int.
Dairy J., 2016, 53, 10–19.
79 S. Patel, A. Majumder and A. Goyal, Indian J. Microbiol.,
2012, 52, 3–12.
80 A. Patel and J. B. Prajapati, Adv. Dairy Res., 2013, 1, 107. DOI:
10.4172/2329-888X.1000107.
81 F. Tidona, S. Francolino, H. Zhang, G. Contarini, S. W. Cui, G.
Giraffa and D. Carminati, J. Food Nutr. Res., 2016, 55, 33–39.
82 P. Duboc and B. Mollet, Int. Dairy J., 2001, 11, 759–768.
83 G. Caggieaniello, M. Kleerebezem and G. Spano, Appl.
Microbiol. Biotechnol., 2016, 100, 3877–3886.
84 S. Galle, C. Schwab, F. Dal Bello, A. Coffey, M. G. Gänzle and
E. K. Arendt, Int. J. Food Microbiol., 2012, 155, 105–112.
85 B. Lebwohl, D. S. Sanders and P. H. R. Green, Lancet, 2018,
391, 70–81.
86 J. West, K. M. Fleming, L. J. Tata, T. R. Card and C. J. Crooks,
Am. J. Gastroenterol., 2014, 109, 757–768.
87 E. K. Arendt, L. A. M. Ryan and F. Dal Bello, Food Microbiol.,
2007, 24, 165–174.
88 K. M. Lynch, E. Zannini, A. Coffey and E. K. Arendt, Annu. Rev.
Food Sci. Technol., 2018, 9, 155–176.
89 Y. Zhang, L. Guo, D. Xu, D. Li, N. Yang, F. Chen, Z. Jin and X.
Xu, Food Chem., 2018, 256, 373–379.
90 G. Kristjánsson, P. Venge and R. Hällgren, Clin. Exp.
Immunol., 2007, 147, 449–455.
91 Y. Doleyres, L. Schaub and C. Lacroix, J. Dairy Sci., 2005, 88,
4146–4156.
92 J. I. Sánchez, B. Martínez, R. Guillén, R. Jiménez-Díaz and A.
Rodríguez, Appl. Environ. Microbiol., 2006, 72, 7495–7502.
93 C. Lindström, O. Holst, L. Nilsson, R. Öste and K. E.
Andersson, AMB Express, 2012, 2, 66.
94 M. I. Torino, G. Font de Valdez and F. Mozzi, Front.
Microbiol., 2015, 6, 834. DOI: 10.3389/fmicb.2015.00834.
95 N. Salazar, M. Gueimonde, A. M. Hernández-Barraco, P.
Ruas-Madiedo and C. G. de los Reyes-Gavilán, Appl. Environ.
Microb., 2008, 74, 4737–4745.
96 N. Salazar, P. Ruas-Madiedo, S. Kolida, M. Collins, R. Rastall,
G. Gibson and C. G. de los Reyes-Gavilán, Int. J. Food
Microbiol., 2009, 135, 260–267.
97 M. Candela, S. Maccaferri, S. Turroni, P. Carnevali and P.
Brigidi, Int. J. Food Microbiol., 2010, 140, 93–101.
98 P. M. Ryan, R. P. Ross, G. F. Fitzgerald, N. M. Caplice and C.
Stanton, Food Funct., 2015, 6, 679–693.
Food Funct, 2018, 00, 1-10 | 9
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99 F. Mozzi, E. Gerbino, G. Font de Valdez and M. I. Torino, J. 127 F. Brighenti, M. C. Casiraghi, E. Canzi and A. Ferrari, Eur. J.
Appl. Microbiol., 2009, 107, 56–64. Clin. Nutr., 1999, 53, 726–733.
100 T. Hongpattarakere, N. Cherntong, S. Wichienchot, S. 128 A. Mortensen, M. Poulsen and H. Frandsen, Nutr. Res.,
Kolida and R. A. Rastall, Carbohydr. Polym., 2012, 87, 846– 2002, 22, 473–480.
852. 129 M. L. Fernandez, S. Roy and M. Vergara-Jimenez, Nutr.
101 D. Das, R. Baruah and A. Goyal, Int. J. Biol. Macromol., Res., 2000, 20, 837–849.
2014, 69, 20–26. 130 W. Shujun, Y. Jinglin, L. Hongyan and C. Weiping, Food.
102 H. Tsuda and T. Miyamoto, Food Sci. Technol. Res., 2010, Chem., 2008, 108, 176–181.
16, 87–92. 131 L. Guo, L. T. Tong, L. Liu, K. Zhong, J. Qiu and S. Zhou,
103 F. Dal Bello, J. Walter, C. Hertel and W. P. Hammes, Lipids Health Dis., 2014, 13, 182.
System. Appl. Microbiol., 2001, 24, 232–237. 132 P. Gunness and M. J. Gidley, Food Funct., 2010, 1, 149–
Published on 18 May 2018. Downloaded by Kaohsiung Medical University on 18/05/2018 14:39:35.

104 R. Baruah, H. M. Ndegwa, K. Katina, R. Juvonen and A. 155.

Goyal, Int. J. Food Microbiol., 2017, 242, 124–131. 133 L. Ellegård and H. Andersson, Eur. J. Clin. Nutr., 2007, 61,

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105 P. Russo, P. López, V. Capozzi, P. F. de Palencia, M. T.
Dueñas, G. Spano and D. Fiocco, Int. J. Mol. Sci., 2012, 13,
6026–6039.
106 A. Hashmi, N. Naeem, Z. Farooq, S. Masood, S. Iqbal and
R. Naseer, Probiotics Antimicrob. Prot., 2016, 8, 19–30.
107 M. Nagaoka, S. Hashimoto, T. Watanabe, T. Yokokura and
Y. Mori, Biol. Pharm. Bull., 1994, 17, 1012–1017.
108 J. Y. Li, M. M. Jin, J. Meng, S. M. Gao and R. R. Lu,
Carbohydr. Polym., 2013, 98, 1147–1152.
109 S. V. Dilna, H. Surya, R. G. Aswathy, K. K. Varsha, D. N.
Sakthikumar, A. Pandey and K. M. Nampoothiri, LWT Food
Sci. Technol., 2015, 64, 1179–1186.
110 M. A. M. Ghoneim, A. I. Hassan, M. G. Mahmoud and M.
S. Asker, BMC Complement. Altern. Med., 2016, 16, 112. DOI:
10.1186/s12906-016-1093-1.
111 C. Rodríguez, M. Medici, A. V. Rodríguez, F. Mozzi and G.
Font de Valdez, J. Dairy Sci., 2009, 92, 2423–2434.
112 M. Oda, H. Hasegawa, S. Komatsu, M. Kambe and F.
Tsuchiya, Agric. Biol. Chem., 1983, 47, 1623–1625.
113 K. Wang, W. Li, X. Rui, X. Chen, M. Jiang and M. Dong, Int.
J. Biol. Macromol., 2014, 63, 133–139.
114 C. Hidalgo-Cantabrana, P. López, M. Gueimonde, C. G. de
Los Reyes-Gavilán, A. Suárez, A. Margolles and P. Ruas-
Madiedo, Probiotics Antimicrob. Prot., 2012, 4, 227–237.
115 I. M. de Paiva, R. da S. Steinberg, I. S. Lula, E. M. de
Souza-Fagundes, T. de O. Mendes, M. J. V. Bell, J. R. Nicoli, A.
C. Nunes and E. Neumann, LWT Food Sci. Technol., 2016, 72,
390–398.
116 C. Matsuzaki, K. Kamishima, K. Matsumoto, H. Koga, T.
Katayama, K. Yamamoto and K. Hisa, J. Appl. Microbiol.,
2014, 116, 980–989.
117 N. Şengül, S. Işık, B. Aslım, G. Uçar and A. E. Demirbağ,
Dig. Dis. Sci., 2011, 56, 707–714.
118 P. F. de Palencia, M. L. Werning, E. Sierra-Filardi, M. T.
Dueñas, A. Irastorza, A. L. Corbí and P. López, Appl. Environ.
Microbiol., 2009, 75, 4887–4891.
119 I. M. Sims, S. A. Frese, J. Walter, D. Loach, M. Wilson, K.
Appleyard, J. Eason, M. Livingston, M. Baird, G. Cook and G.
W. Tannock, ISME J., 2011, 5, 1115–1124.
120 P. Ruas-Madiedo, M. Gueimonde, A. Margolles, C. G. de
los Reyes-Gavilán and S. Salminen, J. Food Prot., 2006, 69,
2011–2015.
121 S. Yusuf, S. Reddy, S. Ôunpuu and S. Anand, Circulation,
2001, 104, 2746–2753.
122 American Heart Association, Circulation, 2017, 135, 146–
603.
123 J. E. Manson, H. Tosteson, P. M. Ridker, S. Satterfield, P.
Hebert, G. T. O’Connor, J. E. Buring and C. H. Hennekens, N.
Engl. J. Med., 1992, 326, 1406–1416.
124 S. Gielen and U. Landmesser, Eur. Heart J., 2014, 35,
307–312.
125 J. L. Causey, J. M. Feirtag, D. D. Gallaher, B. C. Tungland
and J. L. Slavin, Nutr. Res., 2000, 20, 191–201.
126 D. Letexier, F. Diraison and M. Beylot, Am. J. Clin. Nutr.,
2003, 77, 559–564.
938–994.
134 B. Staels and V. A. Fonseca, Diab. Care, 2009, 32, S237–
S245.
135 M. L. Jones, C. Tomaro-Duchesneau, C. J. Martoni and S.
Prakash, Expert Opin. Biol. Ther., 2013, 13, 631–642.
136 B. H. Arjmandi, J. Craig, S. Nathani and R. D. Reeves, J.
Nutr., 1992, 122, 1559–1565.
137 M. Beylot, Br. J. Nutr., 2005, 1, 163–168.
138 Y. Zhao, J. Liu, W. Hao, H. Zhu, N. Liang, Z. He, K. Y. Ma
and Z. Y. Chen, J. Agric. Food Chem., 2017, 65, 10984–10992.
139 R. S. Wright, J. W. Anderson and S. R. Bridges, Proc. Soc.
Exp. Biol. Med.,990, 195, 26–29.
140 M. A. Levrat, M. L. Favier, C. Moundras, C. Rémésy, C.
Demigné and C. Morand, J. Nutr., 1994, 124, 531–538.
141 T. Wolever, P. J. Spadafora, S. C. Cunnane and P. B.
Pencharz, Am. J. Clin. Nutr., 1995, 61, 1241–1247.
142 K. S. Juntunen, D. E. Laaksonen, K. Autio, L. K. Niskanen, J.
J. Holst, K. E. Savolainen, K. H. Liukkonen, K. S. Poutanen and
H. M. Mykkanen, Am. J. Clin. Nutr., 2003, 78, 957–964.
143 H. Mäkeläinen, H. Anttila, J. Sihvonen, R-M Hietanen, R.
Tahvonen, E. Salminen, M. Mikola and T. Sontag-Strohm,
Eur. J. Clin. Nutr., 2007, 61, 779–785.
144 E. Theuwissen and R. P. Mensink, Physiol. Behav., 2008,
94, 285–292.
145 V. Marcil, E. Delvin, C. Garofalo and E. Levy, J. Nutr.,
2003, 133, 2180–2183.
146 S. Tarpila, A. Aro, I. Salminen, A. Tarpila, P. Kleemola, J.
Akkila and H. Adlercreutz, Eur. J. Clin. Nutr., 2002, 56, 157–
165.
147 J. Luo, M. Van Yperselle, S. W. Rizkalla, F. Rossi, F. R. J.
Bornet and G. Slama, J. Nutr., 2000, 130, 1572–1577.
148 P. Sanlibaba and G. A. Çakmak, Appl. Microbiol. OA , 2016,
2, 1000115. DOI: 10.4172/2471-9315.1000115.
149 P. M. Ryan, R. P. Ross, G. F. Fitzgerald, N. M. Caplice and
C. Stanton, Curr. Opin. Clin. Nutr. Metab. Care, 2015, 18,
566–571.
150 H. Maeda, Z. Xia and K. Omura, Biofactors, 2004, 22,
197–201.
151 L. E. E. London, A. H. S. Kumar, R. Wall, P. G. Casey, O.
O’Sullivan, F. Shanahan, C. Hill, P. D. Cotter, G. F. Fitzgerald,
R. P. Ross, N. M. Caplice and C. Stanton, J. Nutr., 2014, 144,
1956–1962.
152 E. Tok and B. Aslim, Microbiol. Immunol., 2010, 54, 257–
264.
153 K. Sasikumar, D. K. Vaikkath, L. Devendra and K. M.
Nampoothiri, Bioresour. Technol., 2017, 241, 1152–1156.
154 B. Bhat and B. K. Bajaj, Bioresour. Technol., 2018, 254,
264–267.
155 M. Uchida, I. Ishii, C. Inoue, Y. Akisato, K. Watanabe, S.
Hosoyama, T. Toida, N. Ariyoshi and M. Kitada, J. Atheroscler.
Thromb., 2010, 17, 980–988.

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Lactic acid bacteria (LAB)-based exopolysaccharides (EPS) potentially have prebiotic properties and
could be natural alternatives for the treatment of hypercholesterolemia

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