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Prebiotics are a group of nutrients that are degraded by gut microbiota. Their relationship with human overall health has been an area of increasing interest in recent years. They can feed the intestinal microbiota, and their degradation products are short-chain fatty acids that are released into blood circulation, consequently, affecting not only the gastrointestinal tracts but also other distant organs. Fructo-oligosaccharides and galacto-oligosaccharides are the two important groups of prebiotics with beneficial effects on human health. Since low quantities of fructo-oligosaccharides and galacto-oligosaccharides naturally exist in foods, scientists are attempting to produce prebiotics on an industrial scale. Considering the health benefits of prebiotics and their safety, as well as their production and storage advantages compared to probiotics, they seem to be fascinating candidates for promoting human health condition as a replacement or in association with probiotics. This review discusses different aspects of prebiotics, including their crucial role in human well-being.
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Prebiotics: Definition, Types, Sources, Mechanisms,
and Clinical Applications
Dorna Davani-Davari 1, Manica Negahdaripour 2,3, Iman Karimzadeh 4, Mostafa Seifan 5, *,
Milad Mohkam 6, Seyed Jalil Masoumi 7, Aydin Berenjian 5and Younes Ghasemi 2,3,7,8,*
1Pharmaceutical Biotechnology Incubator, School of Pharmacy, Shiraz University of Medical Sciences,
Shiraz 71348, Iran;
2Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences,
Shiraz 71348, Iran;
3Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 71348, Iran
4Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences,
Shiraz 71348, Iran;
5Faculty of Science and Engineering, University of Waikato, Hamilton 3216, New Zealand;
6Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz 71348, Iran;
7Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences,
Shiraz University of Medical Sciences, Shiraz 71348, Iran;
8Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies,
Shiraz University of Medical Sciences, Shiraz 71348, Iran
*Correspondence: (M.S.); (Y.G.);
Tel.: +64-07-838-4173 (M.S.); +98-71-324-26729 (Y.G.)
Received: 27 February 2019; Accepted: 5 March 2019; Published: 9 March 2019
Prebiotics are a group of nutrients that are degraded by gut microbiota. Their relationship
with human overall health has been an area of increasing interest in recent years. They can feed the
intestinal microbiota, and their degradation products are short-chain fatty acids that are released
into blood circulation, consequently, affecting not only the gastrointestinal tracts but also other
distant organs. Fructo-oligosaccharides and galacto-oligosaccharides are the two important groups
of prebiotics with beneficial effects on human health. Since low quantities of fructo-oligosaccharides
and galacto-oligosaccharides naturally exist in foods, scientists are attempting to produce prebiotics
on an industrial scale. Considering the health benefits of prebiotics and their safety, as well as their
production and storage advantages compared to probiotics, they seem to be fascinating candidates
for promoting human health condition as a replacement or in association with probiotics. This review
discusses different aspects of prebiotics, including their crucial role in human well-being.
prebiotics; gut microbiota; short-chain fatty acids; fructo-oligosaccharides;
1. Introduction
Various types of microorganisms, known as gut microbiota, are inhabitants of the human
gastrointestinal tract. It has been reported that there are 10
live microorganisms per gram
in the human colon [
]. The resident microbial groups in the stomach, small, and large intestine are
crucial for human health. The majority of these microorganisms, which are mostly anaerobes, live in
the large intestine [2].
Although some endogenous factors, such as mucin secretions, can affect the microbial balance,
human diet is the chief source of energy for their growth. Particularly, non-digestible carbohydrates
Foods 2019,8, 92; doi:10.3390/foods8030092
Foods 2019,8, 92 2 of 27
can highly modify the composition and function of gut microbiota [
]. Beneficial intestinal microbes
ferment these non-digestible dietary substances called prebiotics and obtain their survival energy
from degrading indigestible binds of prebiotics [
]. As a result of this, prebiotics can selectively
influence gut microbiota [
]. On the other hand, the gut microbiota affects intestinal functions,
such as metabolism and integrity of the intestine. Moreover, they can suppress pathogens in healthy
individuals through induction of some immunomodulatory molecules with antagonistic effects against
pathogens by lactic acid that is produced by Bifidobacterium and Lactobacillus genera [811].
Various compounds have been tested to determine their function as prebiotics.
Fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), and trans-galacto-oligosaccharides
(TOS) are the most common prebiotics. Fermentation of prebiotics by gut microbiota produces
short-chain fatty acids (SCFAs), including lactic acid, butyric acid, and propionic acid. These products
can have multiple effects on the body. As an example, propionate affects T helper 2 in the airways
and macrophages, as well as dendritic cells in the bone marrows [
]. SCFAs decrease the pH
of colon [
]. Peptidoglycan is another prebiotics fermentation product that can stimulate the
innate immune system against pathogenic microorganisms [
]. The structure of prebiotics and the
bacterial composition of gut determine the fermentation products [
]. The effects of prebiotics on
human health are mediated through their degradation products by microorganisms. For example,
butyrate influences intestinal epithelial development [
]. Since SCFAs can diffuse to blood circulation
through enterocytes, prebiotics have the ability to affect not only the gastrointestinal tract but also
distant site organs [18].
In this review, we critically elaborate on different aspects of prebiotics, including their definition,
types, sources, mechanisms, and clinical applications.
2. Definition
The prebiotics concept was introduced for the first time in 1995 by Glenn Gibson and Marcel
Roberfroid [
]. Prebiotic was described as “a non-digestible food ingredient that beneficially affects
the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria
in the colon, and thus improves host health”. This definition was almost unchanged for more than
15 years. According to this definition, only a few compounds of the carbohydrate group, such as
short and long chain
-fructans [FOS and inulin], lactulose, and GOS, can be classified as prebiotics.
In 2008, the 6th Meeting of the International Scientific Association of Probiotics and Prebiotics (ISAPP)
defined “dietary prebiotics” as “a selectively fermented ingredient that results in specific changes in
the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host
health” [19].
The following criteria are used to classify a compound as a prebiotic: (i) it should be resistant to
acidic pH of stomach, cannot be hydrolyzed by mammalian enzymes, and also should not be absorbed
in the gastrointestinal tract, (ii) it can be fermented by intestinal microbiota, and (iii) the growth and/or
activity of the intestinal bacteria can be selectively stimulated by this compound and this process
improves host’s health [19].
Although not all the prebiotics are carbohydrates, the following two criteria can be exploited
to distinguish fiber from carbohydrate-derived prebiotics: (i) fibers are carbohydrates with a degree
of polymerization (DP) equal or higher than 3 and (ii) endogenous enzymes in the small intestine
cannot hydrolyze them. It should be taken into account that the fiber solubility or fermentability is not
crucial [20,21].
There are also some revised definitions for prebiotics published in the scientific literature [
However, the above-mentioned definition, which was given in 2008, has been accepted in recent years.
Despite the absence of a consensus definition, the important part of the original and other definitions
is that the consumption of prebiotics is associated with human well-being. The word “selectivity”,
or the potency of a prebiotic to stimulate a specific gut microbiota, was another key element of the
original definition; however, this concept has been questioned recently [
]. In 2013, Scott et al. [
Foods 2019,8, 92 3 of 27
reported that the prebiotic effect was enhanced by cross-feeding, defined as the product of one species
which can be consumed by another one. This implication raises doubt for utilizing the “selectivity”
term in the prebiotics definition. A review on the evolution of prebiotics concept through history can
be found in a previous publication [23], and the debate on their definition is still ongoing [25].
3. Types of Prebiotics
There are many types of prebiotics. The majority of them are a subset of carbohydrate groups and
are mostly oligosaccharide carbohydrates (OSCs). The relevant articles are mainly on OSCs, but there
are also some pieces of evidence proving that prebiotics are not only carbohydrates.
3.1. Fructans
This category consists of inulin and fructo-oligosaccharide or oligofructose. Their structure is a
linear chain of fructose with
1) linkage. They usually have terminal glucose units with
linkage. Inulin has DP of up to 60, while the DP of FOS is less than 10 [2].
Previously, some studies implicated that fructans can stimulate lactic acid bacteria selectively.
However, over recent years, there are some investigations showing that the chain length of fructans is
an important criterion to determine which bacteria can ferment them [
]. Therefore, other bacterial
species can also be promoted directly or indirectly by fructans.
3.2. Galacto-Oligosaccharides
Galacto-oligosaccharides (GOS), the product of lactose extension, are classified into two subgroups:
(i) the GOS with excess galactose at C
, C
or C
and (ii) the GOS manufactured from lactose
through enzymatic trans-glycosylation. The end product of this reaction is mainly a mixture of
tri- to pentasaccharides with galactose in
3), and
4) linkages. This type of GOS is
also termed as trans-galacto-oligosaccharides or TOS [19,27].
GOSs can greatly stimulate Bifidobacteria and Lactobacilli.Bifidobacteria in infants have shown high
incorporation with GOS. Enterobacteria,Bacteroidetes, and Firmicutes are also stimulated by GOS, but to
a lesser extent than Bifidobacteria [2].
There are some GOSs derived from lactulose, the isomer of lactose. This lactulose-derived GOSs
are also considered as prebiotics [
]. Besides these types of GOS, the other types are based on sucrose
extension named raffinose family oligosaccharides (RFO). The effect of RFO on gut microbiota has not
been elucidated yet [28,29].
3.3. Starch and Glucose-Derived Oligosaccharides
There is a kind of starch that is resistant to the upper gut digestion known as resistant starch
(RS). RS can promote health by producing a high level of butyrate; so it has been suggested to be
classified as a prebiotic [
]. Various groups of Firmicutes show the highest incorporation with a high
amount of RS [
]. An
in vitro
study demonstrated that RS could also be degraded by Ruminococcus
bromii, and Bifidobacterium adolescentis, and also to a lesser extent by Eubacterium rectale and Bacteroides
thetaiotaomicron. However, in the mixed bacterial and fecal incubations, RS degradation is impossible
in the absence of R. bromii [31].
Polydextrose is a glucose-derived oligosaccharide. It consists of glucan with a lot of branches
and glycosidic linkages. There is some evidence that it can stimulate Bifidobacteria, but it has not been
confirmed yet [32].
3.4. Other Oligosaccharides
Some oligosaccharides are originated from a polysaccharide known as pectin. This type
of oligosaccharide is called pectic oligosaccharide (POS). They are based on the extension of
galacturonic acid (homogalacturonan) or rhamnose (rhamnogalacturonan I). The carboxyl groups may
Foods 2019,8, 92 4 of 27
be substituted with methyl esterification, and the structure can be acetylated at C
or C
. Various
types of sugars (e.g., arabinose, galactose, and xylose) or ferulic acid are linked to the side chains [
Their structures vary significantly depending on the sources of POSs [34].
3.5. Non-Carbohydrate Oligosaccharides
Although carbohydrates are more likely to meet the criteria of prebiotics definition, there are some
compounds that are not classified as carbohydrates but are recommended to be classified as prebiotics,
such as cocoa-derived flavanols.
In vivo
in vitro
experiments demonstrate that flavanols can
stimulate lactic acid bacteria [35].
4. Production of Prebiotics
Prebiotics play an important role in human health. They naturally exist in different dietary
food products, including asparagus, sugar beet, garlic, chicory, onion, Jerusalem artichoke, wheat,
honey, banana, barley, tomato, rye, soybean, human’s and cow’s milk, peas, beans, etc., and recently,
seaweeds and microalgae [
]. Because of their low concentration in foods, they are manufactured on
industrial large scales. Some of the prebiotics are produced by using lactose, sucrose, and starch as
raw material [
]. Since most prebiotics are classified as GOS and FOS regarding industrial scale
(Figure 1), there are many relevant studies on their production.
Foods 2019, 8, x FOR PEER REVIEW 4 of 27
types of sugars (e.g., arabinose, galactose, and xylose) or ferulic acid are linked to the side chains [33].
Their structures vary significantly depending on the sources of POSs [34].
3.5. Non-Carbohydrate Oligosaccharides
Although carbohydrates are more likely to meet the criteria of prebiotics definition, there are
some compounds that are not classified as carbohydrates but are recommended to be classified as
prebiotics, such as cocoa-derived flavanols. In vivo and in vitro experiments demonstrate that
flavanols can stimulate lactic acid bacteria [35].
4. Production of Prebiotics
Prebiotics play an important role in human health. They naturally exist in different dietary food
products, including asparagus, sugar beet, garlic, chicory, onion, Jerusalem artichoke, wheat, honey,
banana, barley, tomato, rye, soybean, human’s and cow’s milk, peas, beans, etc., and recently,
seaweeds and microalgae [36]. Because of their low concentration in foods, they are manufactured
on industrial large scales. Some of the prebiotics are produced by using lactose, sucrose, and starch
as raw material [37,38]. Since most prebiotics are classified as GOS and FOS regarding industrial scale
(Figure 1), there are many relevant studies on their production.
Figure 1. Sources and production of major prebiotics, including fructo-oligosaccharides (FOS) and
galacto-oligosaccharides (GOS). Prebiotics exist in human diets in small concentration. Since they
have crucial roles in health maintenance, they are manufactured on industrial large scales.
4.1. FOS
FOS exists in about 36,000 plants [39]; however, the concentration of FOS in these sources is not
enough to have prebiotics effects. Therefore, FOS should be synthesized. There are various FOS
production methods, which have been explained by several authors [40,41]. FOS can be synthesized
chemically by using glycosidase and glycosyl-transferase [42]. The compounds that are used in these
reactions are hazardous and costly, and the concentration of the end product (FOS) is very low. Thus,
it cannot be produced on an industrial scale [43]. Fructosyl-transferase (FTase) is a key enzyme in
Figure 1.
Sources and production of major prebiotics, including fructo-oligosaccharides (FOS) and
galacto-oligosaccharides (GOS). Prebiotics exist in human diets in small concentration. Since they have
crucial roles in health maintenance, they are manufactured on industrial large scales.
4.1. FOS
FOS exists in about 36,000 plants [
]; however, the concentration of FOS in these sources is
not enough to have prebiotics effects. Therefore, FOS should be synthesized. There are various FOS
production methods, which have been explained by several authors [
]. FOS can be synthesized
chemically by using glycosidase and glycosyl-transferase [
]. The compounds that are used in these
reactions are hazardous and costly, and the concentration of the end product (FOS) is very low. Thus,
it cannot be produced on an industrial scale [
]. Fructosyl-transferase (FTase) is a key enzyme in
Foods 2019,8, 92 5 of 27
producing FOS. FTase produces FOS from sucrose by transferring one to three molecules of fructose.
Several microorganisms have FTase, such as Fusarium sp., Aspergillus sp., Aureobasidium sp., Penicillium
sp., Arthrobacter sp., Zymomonas mobilis,Bacillus macerans,Candida, Kluyveromyces, and Saccharomyces
cerevisiae [
]. Among these microorganisms, Aspergillus niger and Aureobasidium pullulans are
mostly used in the industry [49].
For FOS production, the whole cell of a microorganism or free enzyme can be used [
There are different factors that can affect the concentration of produced FOS. The maximum amount
of FOS produced by FTases depends on the initial concentration of sucrose (theoretically around
55–60%). Glucose, which is a co-product of fermentation, inhibits trans-glycosylation [
]. Therefore,
removing glucose and sucrose residues is a critical step to achieving higher yields of FOS fermentation.
Some scientists claimed to utilize glucose oxidase and
-fructofuranosidase to enhance the yield of
FOS production [
-fructofuranosidase is capable of converting sucrose to FOS. The glucose
produced during FOS fermentation is converted to gluconic acid by glucose oxidase. Unlike glucose,
gluconic acid is able to be removed by ion-exchange resins or by coagulation with calcium carbonate
) [
]. Thus, the utilization of both enzymes increases the yield of FOS formation up to 98% [
-fructofuranosidase and glucose oxidase can be derived from Apostichopus japonicus and A. niger,
respectively [
]. Glucose can be separated from FOS through nanofiltration methods. This process
increases FOS production by up to 90% [55].
S. cerevisiae and Zymomonas mobilis are able to eliminate small saccharides, such as glucose,
fructose, and sucrose, by converting saccharides to carbon dioxide and ethanol. S. cerevisiae cannot
ferment oligosaccharides with four or more monosaccharide units. Sorbitol and FOS are also produced
in small amounts during fermentation of sucrose by Z. mobilis [5659].
4.2. GOS
GOSs were first chemically synthesized by nucleophilic and electrophilic displacement, but this
method is currently deemed to be uneconomical at the industrial scale [
]. The key enzymes for
GOS formation are galactosyl-transferase and galactosidase. Galactosyl-transferase is a stereoselective
enzyme that can produce GOS in high quantities [
]. Nevertheless, the bio-catalysis of GOS via
galactosyl-transferase is so costly, because this reaction needs nucleotide sugars as a donor. There are
some approaches to decrease the cost of this reaction, such as globotriose production [60,62] or using
human milk oligosaccharides [63,64].
Formation of GOS by means of galactosidase is much cheaper than galactosyl-transferases.
However, galactosidase produces GOS in lower quantities, and this enzyme is less stereospecific than
galactosyl-transferase. The amount of GOS produced by galactosidase can be improved in different
ways: (i) increasing the concentration of donors and acceptors in the reaction, (ii) lowering water
activity of the reaction, (iii) shifting the reaction equilibrium to the end product direction by the product
elimination in the medium, and (iv) altering the synthesis conditions [60,65].
-Galactosidases come from different sources, such as Aspergillus oryzae,Sterigmatomyces elviae,
Bifidobacteria, and Lactobacilli. Different sources of
-galactosidases cause various types of GOS that
differ in the amount, DP, and glycosidic linkages [
]. Various sources of
-galactosidases need
different conditions for optimizing GOS production. For example, fungal and bacterial, as well as
yeast sources, require acidic and neutral pH, respectively. Furthermore, high temperature necessitates
for thermophilic sources. These conditions have been optimized in various studies [66,7073].
For GOS bio-catalysis, the whole cell or just the free form of
-galactosidase can be used.
The recombinant form of this enzyme is also available. The whole cell is exploited when the
-galactosidase isolation process is uneconomical [
]. The utilization of the whole cell is also much
cheaper due to co-factors that naturally exist in the cell and cell membrane [
], but it is not very
crucial for GOS synthesis because β-galactosidase uses metal ions as co-factors.
There are some by-products, such as glucose and galactose, which do not have prebiotic effects and
may decrease GOS synthesis yield. When the whole cell is used, these by-products can be removed by
Foods 2019,8, 92 6 of 27
other metabolic processes. For instance, Sirobasidium magnum,S. elviae, and Rasopone minuta consume
glucose as a carbon source when cultured on lactose medium for GOS synthesis [
]. As another
example, galactose can induce the expression of
-galactosidase, and glucose is utilized as a carbon
source in yeast cells [
]. However, some metabolic end products, including ethanol, lactic acid,
and acetic acid, are produced, when viable whole cells are used, which can affect GOS production.
Therefore, other methods are required to remove these metabolic products. Apart from the interference
of metabolic end products with GOS production, the temperature is another unfavorable factor when
using the whole cell. Temperature often increases the yield of GOS synthesis, which is undesirable
and even fatal for non-thermophilic cells. In some studies, non-viable and resting cells are exploited.
These kinds of cells do not have the drawbacks of viable cells, and their GOS production yields are
much higher [57,66,83].
-galactosidases have more advantages than native
-galactosidases, such as
high production yield, easy purification, and improved enzyme stability, as well as an activity
through molecular approaches [
]. Escherichia coli and Bacillus subtilis are mostly used for producing
-galactosidases. E. coli has some disadvantages, such as endotoxins production, difficulty
in disulfide bonds expression, and acetate formation, which has toxic effects [
]. In contrast,
the engineered
B. subtilis does not produce any endo- or exo-toxins. But this bacterium has also some
disadvantages, including producing proteases in high quantities (which are able to degrade proteins)
and plasmid instability [86,87].
Some yeasts, such as S. cerevisiae and Pichiapastoris, have been used for producing recombinant
forms of
-galactosidase. Yeast has some advantages as compared to bacteria, including (i) higher
range of productivity, (ii) disulfide bond production, and (iii) better protein folding [86,88,89].
5. Prebiotics Mechanisms for Alteration of Gut Microbiota
By the provision of energy sources for gut microbiota, prebiotics are able to modulate the
composition and the function of these microorganisms [
]. Distant bacterial species in phylogeny
share their skills to consume a specific prebiotic regularly [
]. It has also been recently reported by a
functional metagenomics technique. In this method, genes from a human microbiota metagenomic
library are identified for the breakdown of several prebiotics in a heterologous host, such as E. Coli [
Clones from various species, such as Actinobacteria,Bacteroidetes, and Firmicutes, can ferment FOS, GOS,
and xylooligosaccharides (XOS). In contrast, some other studies report that specific species can degrade
a given prebiotic. Fermentation of starch [
] and fructans [
] by Bifidobacterium sp. are examples
in this regard. Another important factor for distinguishing species that are capable of fermenting a
specific prebiotic is their chain length. For example, inulin (with DP of
60) can be fermented only
by a few species, whereas a large number of microorganisms are able to degrade FOS (with DP of
10) [26].
Sometimes, a by-product of a complex prebiotic’s fermentation is a substrate for another
microorganism, called cross-feeding [
]. For example, Ruminococcus bromii can degrade resistant
starches, and several species can utilize the fermentation products of this reaction [
]. At the same
time, some products may have antagonistic effects on other species.
Prebiotics are also able to modify the environment of the gut. As mentioned before, fermentation
products of prebiotics are mostly acids, which decrease the gut pH. It has been shown that one unit
alteration in the gut pH from 6.5 to 5.5 can contribute to a change in the composition and population
of the gut microbiota [
]. The pH alteration can change the population of acid-sensitive species,
such as Bacteroids, and promote butyrate formation by Firmicutes. This process is called butyrogenic
effect [96].
6. Prebiotics Mechanisms for Health Maintenance and Protection against Disorders
As it was mentioned earlier, the products of prebiotics degradation are mainly SCFAs. These
molecules are small enough to diffuse through gut enterocytes and enter blood circulation. Therefore,
Foods 2019,8, 92 7 of 27
prebiotics are able to affect not only the gastrointestinal track but also other distant site organs and
systems [18] (Figure 2).
Foods 2019, 8, x FOR PEER REVIEW 7 of 27
Figure 2. Prebiotics effects for health maintenance and protection against disorders. Prebiotics not
only have protective effects on the gastrointestinal system but also on other parts of the body, such as
the central nervous system, immune system, and cardiovascular system. TAG: triacylglycerol; LDL:
low-density lipoprotein; IBS: irritable bowel syndrome; IL-4: interleukin 4; IL-8: interleukin 8; IL-10:
interleukin 10; NK cells function: natural killer cells function.
6.1. Prebiotics and Gastrointestinal Disorders
6.1.1. Irritable Bowel Syndrome and Crohn’s Disease
There are a few studies about the effects of prebiotics on irritable bowel syndrome (IBS) and
Crohn’s disease. IBS is a gastrointestinal syndrome characterized by chronic abdominal pain and
altered bowel habits in the absence of any organic cause. Crohn's disease is a type of chronic,
relapsing inflammatory bowel disease (IBD), which can involve any part of the gastrointestinal tract
from the mouth to the anus. It has been reported that in both IBS and Crohn’s disease, the
Bifidobacteria and Faecalibacterium prausnitzii population along with Bacteroides to Firmicutes ratio were
decreased [29,98].
A double-blind cross-over study demonstrated that the administration of oligofructose at the
dose of 6 g/day for 4 weeks had no therapeutic effects on patients suffering from IBS [99]. Similarly,
another randomized, double-blind, placebo-controlled trial published in 2000 implicated that 20
g/day FOS supplementation failed to improve IBS [100]. In contrast, two more recent randomized,
double-blind, clinical trials have shown IBS symptoms improvement after consuming 5 g/day FOS
for 6 weeks [101] or 3.5 g/day GOS for 12 weeks [102].
A group study in 2006 reported that supplementation with 15 g/day FOS for 3 weeks elevated
Bifidobacteria population in the feces and improved Crohn’s disease [103]. However, the other
randomized, double-blind, and placebo-controlled trials demonstrated no clinical benefits after
administrating 15 g/day FOS in patients with active Crohn’s disease [104] and 20 g/day oligofructose-
Figure 2.
Prebiotics effects for health maintenance and protection against disorders. Prebiotics not
only have protective effects on the gastrointestinal system but also on other parts of the body, such as
the central nervous system, immune system, and cardiovascular system. TAG: triacylglycerol; LDL:
low-density lipoprotein; IBS: irritable bowel syndrome; IL-4: interleukin 4; IL-8: interleukin 8; IL-10:
interleukin 10; NK cells function: natural killer cells function.
6.1. Prebiotics and Gastrointestinal Disorders
6.1.1. Irritable Bowel Syndrome and Crohn’s Disease
There are a few studies about the effects of prebiotics on irritable bowel syndrome (IBS) and
Crohn’s disease. IBS is a gastrointestinal syndrome characterized by chronic abdominal pain and
altered bowel habits in the absence of any organic cause. Crohn’s disease is a type of chronic, relapsing
inflammatory bowel disease (IBD), which can involve any part of the gastrointestinal tract from the
mouth to the anus. It has been reported that in both IBS and Crohn’s disease, the Bifidobacteria and
Faecalibacterium prausnitzii population along with Bacteroides to Firmicutes ratio were decreased [
A double-blind cross-over study demonstrated that the administration of oligofructose at the dose
of 6 g/day for 4 weeks had no therapeutic effects on patients suffering from IBS [
]. Similarly, another
randomized, double-blind, placebo-controlled trial published in 2000 implicated that 20 g/day FOS
supplementation failed to improve IBS [
]. In contrast, two more recent randomized, double-blind,
clinical trials have shown IBS symptoms improvement after consuming 5 g/day FOS for 6 weeks [
or 3.5 g/day GOS for 12 weeks [102].
A group study in 2006 reported that supplementation with 15 g/day FOS for 3 weeks
elevated Bifidobacteria population in the feces and improved Crohn’s disease [
]. However,
the other randomized, double-blind, and placebo-controlled trials demonstrated no clinical benefits
Foods 2019,8, 92 8 of 27
after administrating 15 g/day FOS in patients with active Crohn’s disease [
] and 20 g/day
oligofructose-enriched inulin in patients with inactive or mild-to-moderately active Crohn’s
disease [105] for a duration of 4 weeks.
6.1.2. Colorectal Cancer
Colorectal cancer, ranked as the third most common malignancy worldwide, is a multi-step
disease from genetic mutation to adenomatous polyps, which then leads to invasive and metastatic
cancer [
]. It has been demonstrated that prebiotics fermentation products, such as butyrate, could
have protective effects against the risk of colorectal cancer, as well as its progression, via inducing
apoptosis [
]. In addition, a clinical trial demonstrated that symbiotic therapy (Lactobacillus
rhamnosus and Bifidobacterium Lactis plus inulin) could reduce the risk of colorectal cancer by reducing
the proliferation rate in colorectal, inducing colonic cells necrosis, which leads to improving the
integrity and function of epithelial barrier [106,109,110].
6.1.3. Necrotizing Enterocolitis
Necrotizing enterocolitis (NEC) is a gastrointestinal emergency condition primarily in premature
neonates, in which portions of the bowel undergo necrosis. It can lead to high morbidity and mortality
rates [
]. Since prebiotics, such as FOS and GOS, can stimulate the growth of gut microbiota (e.g.,
Bifidobacteria) and reduce the pathogenic bacteria in preterm infants [
], it is claimed that they
can prevent NEC [
]. Moreover, SCFAs can improve feeding tolerance by enhancing both gastric
emptying and bowel motility [
]. A meta-analysis of four randomized controlled trials showed
that FOS, GOS or their mixture could elevate the concentration of fecal Bifidobacteria, but had no
significant effect on risk reduction and progression of NEC [
] (Table 1). Therefore, more clinical
trials need to be done to elucidate the definite effects of prebiotics on NEC.
Table 1. Studies showing the effect of prebiotics on the gastrointestinal tract.
Prebiotic Dose Subjects Main Results Reference
6 g/day for 4 weeks Patients with IBS No therapeutic effect. [99]
20 g/day for 12 weeks Patients with IBS No therapeutic effect. [100]
5 g/day for 6 weeks Patients with IBS
Improvement in IBS syndromes.
15 g/day for 3 weeks Patients with active
ileocolonic Crohn’s disease Crohn’s disease improvement. [103]
15 g/day for 4 weeks Patients with Crohn’s disease No clinical improvement in
Crohn’s disease. [104]
GOS 3.5 g/day for 12 weeks Patients with IBS
Improvement in IBS syndromes.
Mixture of FOS
and GOS
0.8 g/dL of a mixture of GOS
and FOS, ratio 9:1 for 30 days Healthy newborns Improvement in gastric
emptying and bowel motility. [115]
0.8 g/dL of a mixture of GOS
and FOS, ratio 9:1 for 15 days Healthy newborns Improvement in gastric
emptying and bowel motility. [116]
20 g/day for 4 weeks
Patients with inactive and
mild to moderately active
Crohn’s disease
No clinical Improvement in
Crohn’s disease. [105]
Raftilose®Synergy 1 +
Bifidobacterium lactis Bb12,
Lactobacillus rhamnosus GG
HT29 or CaCo-2 cells
Cell growth inhibition. As a
result, this mixture can decrease
the progression of colorectal
Different doses Rats with colon carcinogen
Long-chain inulin effects are
dose-dependent on colorectal
Synergy 1 + Bifidobacterium
lactis Bb12, Lactobacillus
rhamnosus GG
Colon cancer patients and
polypectomized patients
Decrease in the progression of
colorectal cancer. [110]
Lactose 25 g daily for 15 days Lactose malabsorbers Improvement in lactose
digestion. [117]
FOS: Fructo-oligosaccharides; IBS: irritable bowel syndrome; and GOS: Galacto-oligosaccharides.
Foods 2019,8, 92 9 of 27
6.2. Prebiotics and the Immune System
Consuming prebiotics can improve immunity functions by increasing the population of protective
microorganisms. Animal and human studies have shown that prebiotics can decrease the population
of harmful bacteria by Lactobacilli and Bifidobacteria [
]. For example, mannose can reduce
colonization of pathogens by promoting mannose adhesion to Salmonella. Mannose binds to Salmonella
via type 1 fimbriae (finger-like projections) [
]. In addition, pathogens are not able to bind to the
epithelium in the presence of OSCs. Prebiotics can also induce the expression of immunity molecules,
especially cytokines (Table 2).
Interestingly, maternal prebiotics metabolites are able to cross the placenta and can affect the
development of the fetal immune system [
]. In 2010, Fugiwara et al. [
] reported that FOS
administration in a pregnant mouse model modified offspring microbiota, and consequently, their skin
inflammation was attenuated. In contrast, Shadid et al. [
] in a placebo-controlled, randomized, and
double-blinded study demonstrated that bifidogenic effects of prebiotics supplementation in humans
could not be transferred to the next generation. The details of well-known prebiotic effects on the
immune systems are discussed below:
Oligofructose and inulin mixture: The mixture of oligofructans and inulin can improve antibody
responses toward viral vaccines, such as influenza and measles [129].
FOS: Studies have shown the improvement of antibody response to influenza vaccine following
FOS consumption. Moreover, the side effects of the influenza vaccine are reduced [
Diarrhea-associated fever in infants is also reduced by this category of prebiotics. Apart from
these, it can decrease the use of antibiotics, duration of disease, and the incidence of febrile
seizures in infants [
1) fructans can up-regulate the level of interleukin 4 (IL-4)
in serum, CD282+/TLR2+ myeloid dendritic cells, and a toll-like receptor 2-mediated immune
response in healthy volunteers [
]. In contrast, another study demonstrated that the salivary
immunoglobulin A (IgA), immune cells in serum, and activation and proliferation of T cells
and natural killer (NK) cells were not changed after consuming
1) fructans [
]. It has
been noted that FOS reduces the risk of some immune diseases in infants, such as atopic
. This type of prebiotic decreases the expression of IL-6 and phagocytosis in
monocytes and granulocytes [138].
GOS: Studies showed that GOS increased the blood level of interleukin 8 (IL-8), interleukin 10
(IL-10), and C-reactive protein in adults, but decreased IL-1
. It has been found that the function
of NK cells improves by consuming GOS [
]. In infants, GOS reduces the risk of atopic
dermatitis and eczema [136,137,141].
AOS (acidic oligosaccharides): The possibility of atopic dermatitis is reduced by AOS in low-risk
infants [136].
Foods 2019,8, 92 10 of 27
Table 2. Studies showing the effect of prebiotics on the immune system.
Prebiotic Dose Subjects Main Results Reference
8 oz/day of an experimental formula containing
FOS for 183 days Adults aged 65 and older
Antibody responses toward viral vaccines
Hospitalization due to influenza and side
effects of influenza vaccines decreased.
8 g/day Orafti®Synergy1 for 8 weeks Adults aged 45–63 years Immune responses toward influenza vaccines
improved. [135]
0.55 g FOS per 15 g of cereal for 6 months Non-breast-feeding infants aged
4–24 months
Diarrhea associated fever, febrile seizure
incident, antibiotics usage, and duration of
infectious disease decreased.
3×5 g/day FOS consisted of two 28 day
treatments separated by a 14-day washout Healthy volunteers
IL-4 in serum, CD282+/TLR2+ myeloid
dendritic cells, and toll-like receptor
2-mediated immune response were
Not exactly defined Infants Risk of some immune diseases, such as atopic
dermatitis, reduced. [136,137]
2×4 g/day for 3 weeks Elderly nursing home patients
IL-6 expression and phagocytosis in monocytes
and granulocytes decreased. [138]
8 g/day Orafti®Synergy1 for 4 weeks Adults aged 45–65 years
Salivary IgA, immune cells in serum,
activation, and proliferation of T and NK cell
not changed.
5.5 g/day for 10 weeks Elderly subjects
Phagocytosis, NK cell activity, and IL-10 (an
anti-inflammatory cytokine) level increased.
Pro-inflammatory cytokines, such as IL-6,
IL-1β, and tumor necrosis factor-α, levels
5.5 g/day consisted of two 10 weeks of treatment
separated by 4 weeks of washout Elderly subjects
IL-10, IL-8, C-reactive protein, and NK cell
activity elevated.
IL-1βlevel decreased.
Not exactly defined Infants
Risk of some immune diseases, such as atopic
dermatitis, reduced.
0.8 g/100 mL Infants [137]
0.8 g/day for 6 months Newborn infants [141]
AOS Not exactly defined Infants Atopic dermatitis in low-risk infants reduced. [136]
Oligofructose and inulin
Oligofructose (70%) and inulin (30%) with a
concentration of 1 g per 25 g of dry weight cereal
during 4 weeks prior to measles vaccination
Infants aged 7–9 months Antibody responses toward viral vaccines
improved. [129]
FOS: Fructo-oligosaccharides; IBS: irritable bowel syndrome; GOS: Galacto-oligosaccharides; AOS: acidic oligosaccharides; NK cell: natural killer cell; IL-4: interleukin 4; IL-10: interleukin
10, IL-8: interleukin 8; and IL-6: interleukin 6.
Foods 2019,8, 92 11 of 27
6.3. Prebiotics and the Nervous System
The gastrointestinal tract is connected to the central nervous system through the “gut-brain
axis” [
]. For instance, administration of prebiotics in piglets decreases the gray matter in order
to improve neural pruning [
]. But the regulatory effects of prebiotics on the human brain have
not been completely defined. Gut microbiota affects the brain through three routes, including neural,
endocrine, and immune pathways [142,144,145].
Neural Pathway: The products of prebiotics fermentation can affect the brain by the vagus
nerve [
]. Some prebiotics, such as FOS and GOS, have regulatory effects on brain-derived
neurotrophic factors, neurotransmitters (e.g., d-serine), and synaptic proteins (e.g., synaptophysin
and N-methyl-D-aspartate or NMDA receptor subunits) [147,148].
Endocrine Pathway: Hypothalamic-pituitary-adrenal axis is a neuroendocrine pathway.
The microbiome growth in mice can induce corticosterone and adrenocorticotropic hormone in
an appropriate way [
]. In addition, prebiotics act as a regulator of other hormones, such as
plasma peptide YY [147].
Immune Pathway: As discussed before, prebiotics can affect different aspects of the immune
system. Beside neurological functions, prebiotics are also capable of influencing mood, memory,
learning, and some psychiatry disorders by changing the activity and/or composition of gut
microbiota [145] (Table 3).
IV- Mood: Stress hormones are able to affect anxiety-related behaviors [
]. It was demonstrated
that the level of stress hormones (adrenocorticotropic hormone (ACTH) and corticosterone)
increased in germ-free mice following exposure to controlled stress. After administrating
Bifidobacterium infantis, corticosterone and ACTH reached normal levels [149].
Memory, concentration, and learning: Recently, a number of studies have shown the relation between
memory and administration of fermentable compounds in both animals and humans [
Investigations on a different kind of prebiotics have implicated memory improvement in
middle-aged adults [
]. Some prebiotics, such as arabinoxylan and arabinose, can enhance
general cognition and attenuate the accumulation process of dementia-related glial fibrillary acidic
protein in mice [
]. Prebiotics may be more efficient in preserving recall and learning rather
than the development process. In 2015, a randomized, double-blind, and placebo-controlled
study was performed to examine the effects of FOS and GOS daily consumption for three weeks
on the level of salivary cortisol and emotional alteration regarding this hormone. FOS had no
significant effect, but 5.5 g GOS intake increased the level of cortisol in saliva and enhanced the
concentration in adults [
]. A randomized, double-blind, placebo-controlled trial demonstrated
that administration of non-starch polysaccharides (3.6 g per day) for twelve weeks enhanced
recall and memory processes in the middle-aged adult [
]. In contrast, the mixture of FOS,
GOS, and AOS could not enhance the development of the nervous system in preterm infants after
24 months [
]. In two other clinical investigations, Smith et al. observed that administration
of inulin-enriched oligofructose might enhance mood, recognition, immediate memory, and
recall (after 4 hours). However, this prebiotic failed to recover long-term memory (after
43 days) [
]. In another study, administration of polydextrose and GOS mixture decreased
anxiety-like behavior in male piglets and promoted positive social interactions in rats [
Furthermore, the consumption of this mixture boosted their cognition memory [160,161].
Autism: 70% of people with autism are suffering from concomitant gastrointestinal disorders
compared to 9% of healthy individuals. Chronic constipation (and other diseases as a result
of constipation), abdominal pain with or without diarrhea, gastroesophageal reflux disease,
abdominal bloating, disaccharide deficiencies, gastrointestinal tract inflammation, and enteric
nervous system abnormalities are examples of gastrointestinal symptoms and signs that are
reported for patients with autism spectrum disorders [
]. The severity of autism is shown to be
correlated to higher gastrointestinal disorders [
]. Interestingly, a review article published in
Foods 2019,8, 92 12 of 27
2016 confirmed these statements [
]. The composition of gut microbiota is changed in patients
with autism disorders. Some studies have shown high levels of Clostridium and depleted
Bifidobacterium in feces. In children with autism, gut metabolites are different from healthy
individuals. For example, the amount of SCFAs in children with autism is lower than healthy
ones [
]. Various prebiotics, such as wheat fiber, may have therapeutic effects on patients
with autism by decreasing the population of Clostridium perfringens and increasing the rate of
Bifidobacteria [
]. Catecholamines, which are a category of neurotransmitters, are increased
in individuals with autism. These neurotransmitters are produced by tyrosine hydroxylase.
in vitro
study in a rat adrenal medulla cell line demonstrated that SCFAs, the products of
prebiotic fermentation, could induce the expression of tyrosine hydroxylase [
]. However,
further investigations are required to understand which prebiotics have therapeutic effects on
human autism.
Hepatic encephalopathy: Hepatic encephalopathy happens when the liver does not function
properly. The main reason for hepatic encephalopathy is the increases in the level of blood
ammonia. This condition causes numerous psychiatric and neurologic complications, including
personality, speech, and movement disorders, as well as cognition impairment, and may
eventually result in coma and death. In 1966, it was demonstrated that lactulose could effectively
treat hepatic encephalopathy by decreasing the level of ammonia in the gut. Lactulose can
improve the life quality of people suffering from hepatic encephalopathy. This prebiotic also
has preventive effects on hepatic encephalopathy [
]. Lactulose exerts its beneficial
effects on hepatic encephalopathy through different pathways. First, the product of lactulose
fermentation is lactic acid, which is able to reduce the colonic lumen pH by releasing H
The ammonia in the gut reacts with proton and produces ammonium. This conversion develops
a concentration gradient that increases the amount of ammonia reuptake from the blood into
the gastrointestinal tract [
]. Second, in the presence of lactulose in the gastrointestinal tract,
the bacteria utilize the energy of lactulose fermentation instead of the conversion of amino acids
to ammonia energy. Third, lactulose can inhibit glutaminase and prevent the production of
ammonia from glutamine [
]. Finally, lactulose shortens the colonic transit time. Thus, it can
reduce the level of ammonia in the gastrointestinal tract. Other compounds, such as lactitol,
may also be as effective as lactulose in the treatment of hepatic encephalopathy. Interestingly,
the side effects of lactitol are much fewer than lactulose (e.g., flatulence and nausea) [172174].
Foods 2019,8, 92 13 of 27
Table 3. Studies showing the effect of prebiotics on the nervous system.
Prebiotic Dose Subjects Main Results Reference
Non-starch polysaccharides (NSPs) 4 g of NSPs (Ambrotose®)Middle-aged healthy adults Recognition and working memory
performance improved. [153]
3.6 g/day for 12 weeks Middle-aged healthy adults Cognitive function and well-being optimized. [154]
Mixture of FOS, GOS, and AOS
Supplementation between day 3 and 30 of life, and
the results measured during 24 months Preterm infants Neurodevelopment did not improve
significantly. [157]
Inulin-enriched oligofructose
5 g, the results measured after 4 h 19–30 years old healthy individuals Mood, recognition, immediate memory, and
recall enhanced. [158]
10 g/day of Synergy
1, the results measured after
43 days 19–64 years old healthy individuals Long-term memory did not change
significantly. [159]
Mixture of GOS and polydextrose
2.4 and 7 g/L of polydextrose and GOS Male piglets They may have neurodevelopment effect in
human infants. [143]
7 g/kg prebiotics mixture Rats Memory and social behaviors improved, and
anxiety-like behaviors reduced. [160]
15 g/kg prebiotics mixture Mice
Water extract of Triticum aestivum
composed of arabinoxylan, β-glucan,
and arabinose
- Rats
Arabinoxylan, β-glucan, and arabinose had
preserved cognition effects against vascular
GOS 5.5 g/day for 3 weeks 18–45 years old healthy volunteers
Salivary cortisol awakening response was
decreased, attentional vigilance to negative
versus positive information reduced, and the
concentration improved.
Lactoferrin (0.6 g/L) and Milk fat globule
membrane (MFGM) (5.0 g/L) Male piglets
Lactulose appeared to have neurodevelopment
effect in human infants. [143]
Duphalac®90–150 mL/d Patients with chronic portal-systemic
encephalopathy (PSE) Blood ammonia levels decreased. [168]
30–60 mL of lactulose in 2 or 3 divided doses for
3 months Patients with cirrhosis Cognitive function and health-related quality
of life improved. [169]
Meta-analysis Patients with subclinical hepatic
Lactulose had the most beneficial influence
among prebiotics and probiotics. [170]
67 mg/day for long-term therapy (1 to 10 months)
Patients with chronic PSE The lower intestinal tract was acidified, and
lactulose had a beneficial effect on chronic PSE.
NSPs: non-starch polysaccharides; FOS: Fructo-oligosaccharides; GOS: Galacto-oligosaccharides; and AOS: acidic oligosaccharides.
Foods 2019,8, 92 14 of 27
6.4. Prebiotics and Skin
As mentioned in the previous sections, the consumption of prebiotics was shown to decrease the
risk of development, as well as the severity of allergic skin diseases, such as atopic dermatitis [
In hairless mice exposed to the UV, the consumption of GOS for 12 weeks enhanced water retention
and also prevented the development of erythema [
]. On the other hand, GOS can improve skin
barrier by increasing dermal expression of cell adhesion and matrix formation markers (e.g., CD44
and collagen type 1). Upon metabolizing aromatic amino acids by gut microbes, some compounds,
such as phenols, may be produced. These compounds are transferred into the skin. Phenols, such as
p-cresol, may be toxic for patients with underlying kidney diseases [
]. In women, consumption of
GOS with or without probiotics, such as Bifidobacterium breve, can abolish the reduction of water and
keratin caused by phenols [177180] (Table 4).
Table 4. Studies showing the effect of prebiotics on the skin.
Prebiotic Dose Subjects Main Results Reference
AOS Not exactly defined Infants
Formula supplementation
with a specific mixture of
oligosaccharides was effective
in preventing atopic
dermatitis in low-risk infants.
Not exactly defined Infants
Risk of some immune diseases,
such as atopic dermatitis,
0.8 g/100 mL Infants [137]
0.8 g/day for 6 months Newborn infants [141]
GOS with or
without probiotics
100 mg of GOS daily for
12 weeks
Hairless mice exposed to
the UV
Water retention enhanced, and
erythema reduced. [175]
600 mg of GOS for 4 weeks Adult healthy women Water and keratin reduction
caused by phenols decreased. [177]
6.5. Prebiotics and Cardiovascular System
According to the statistics, 30% of the deaths in the United States in 2013 were caused by
cardiovascular diseases (CVD). The main reason for this growing trend is the alteration of people’s
lifestyles and eating habits [
]. Therefore, many researchers have studied the influence of fibers
and prebiotics consumption on CVD. However, the direct beneficial functions of prebiotics in this
regard have not been demonstrated yet. In this section, we summarized some of the indirect effects of
prebiotics on CVD.
Prebiotics are able to lower the risk of CVD by reducing the inflammatory elements. Several
investigations demonstrated an improvement in the lipid profile by consuming prebiotics. In a
randomized, double-blind, and placebo-controlled crossover clinical trial, Letexier et al. [182] treated
healthy individuals with 10 g/day inulin for three weeks. They observed that this regimen decreased
blood triacylglycerol (TAG) and liver lipogenesis, but it had no statistically significant effect on the
cholesterol level.
In line with these findings, in a randomized and double-blinded cross-over trial, Russo et
al. [
] demonstrated that the consumption of inulin-enriched pasta with a formulation of 86%
semolina, 11% inulin, and 3% durum wheat vital gluten decreased both TAG and lipogenesis in
healthy individuals, rather than cholesterol level. In contrast, Frochen and Beylot [
] reported
that the consumption of 10 g/day inulin-type fructans for six months had no significant effects on
lipogenesis in the liver of healthy subjects.
To assess the effects of oral L-rhamnose and lactulose on lipid profile in a partially randomized
crossover study, Vogt et al. [
] administered 25 g/day of these two prebiotics for four weeks in
healthy individuals. They observed a significant reduction in the synthesis and level of TAG but not
cholesterol. Opposed to that, the results of another investigation in 1991 suggested that lactulose
increased blood cholesterol (up to 10%) and B-apolipoprotein (up to 19%) [186].
In a double-blind, randomized, placebo-controlled, crossover study on overweight subjects with
3 risk factors of metabolic syndrome, Bimuno
Galacto-oligosaccharides (B-GOS) administration for
Foods 2019,8, 92 15 of 27
12 weeks decreased circulating cholesterol, TAG, and total:HDL (high-density lipoprotein) cholesterol
ratio [
]. However, in the elderly, this prebiotic had no significant effect on the total:HDL cholesterol
ratio [
]. The effect of
-glucan intake on lipid profile was measured in a meta-analysis study (from
1990 through Dec. 2009). It was implicated that
-glucan consumption could reduce the level of total
cholesterol and LDL [
]. Finally, a meta-analysis of relevant randomized controlled clinical trials
published between 1995 and 2005 implicated that FOS could reduce TAG level with an average rate of
7.5% [189].
Paradoxically, prebiotics may have a detrimental effect on lipid profile through producing some
SCFAs, such as acetate. Acetate can be converted to acetyl-CoA, which is a substrate to synthesize fatty
acids in hepatocytes [
]. This can justify the increase in the blood concentration of cholesterol and
triglycerides after rectal infusion of acetate [
]. However, some other SCFAs, such as propionate
and butyrate, may improve lipid profile. Propionate can inhibit lipid synthesis from acetate [
Therefore, prebiotics, such as FOS and L-rhamnose, may have lipogenic effects by producing acetate,
butyrate, and propionate [
]. Hence, it is crucial to determine the end products of prebiotics
to select the appropriate one for this purpose. Although prebiotics are claimed to be beneficial for
obesity-related diseases, such as fatty liver disease, particularly, non-alcoholic fatty liver issue in one
study [194], there is at least another clinical trial that refuted this opinion [195] (Table 5).
Table 5. Studies showing the effect of prebiotics on the cardiovascular system.
Prebiotic Dose Subjects Main Results Reference
2-weeks run-in period, a
baseline assessment, two
5-weeks study periods (11%
inulin-enriched or control
Healthy individuals
HDL-cholesterol level elevated; total
cholesterol/HDL-cholesterol ratio,
triglycerides, and lipoprotein A levels
Inulin 10 g/day for 3 weeks Healthy individuals Hepatic lipogenesis and plasma
triacylglycerol concentrations reduced. [182]
Mixture of inulin
and oligofructose 10 g/day for 6 months Healthy individuals
Plasma triacylglycerol concentrations
and hepatic lipogenesis were not
changed. A non-significant decreasing
trend in plasma total and low-density
lipoprotein cholesterol levels were
observed, and high-density lipoprotein
cholesterol concentration increased.
L-rhamnose 25 g/day for 4 weeks Healthy adults
Triacylglycerol (TAG) and net TAG-fatty
acid (TAGFA) synthesis decreased. [185]
Lactulose 25 g/day for 4 weeks Healthy adults
Triacylglycerol (TAG) and net TAG-fatty
acid (TAGFA) synthesis decreased. [185]
18–25 g/day for 2 weeks Healthy individuals
Free fatty acid concentrations were
reduced by increasing the absorbed
acetate from the colon.
GOS Administrating Bi2muno
(B-GOS) for 2 six weeks
Overweight subjects
with 3 risk factors of
metabolic syndrome
Circulating cholesterol, TAG, and
total:HDL cholesterol ratio decreased. [187]
6.6. Prebiotics and Calcium Absorption
Statistics have shown that more than 28 million people in the United States have osteoporosis or
low bone mass, and in European Union, one out of eight citizens over 50 years old have spinal fracture
each year [
]. There are clinical trials on the impact of prebiotics dietary fibers on the absorption of
minerals, such as calcium, but the results are conflicting. Some studies have shown that consumption
of lactulose, TOS or inulin + oligofructose in doses ranged between 5 to 20 g/day significantly absorb
calcium absorption. In contrast, such a phenomenon is not observed for GOS or FOS (Table 6) [197].
Foods 2019,8, 92 16 of 27
Table 6. Studies showing the effect of prebiotics on mineral absorption.
Prebiotic Dose Subjects Main Results Reference
Inulin or oligofructose
17 g of inulin or oligofructose
and 7 g for three experimental
periods of three days each.
Patients with
conventional ileostomy
because of ulcerative
No significant effect on
calcium, magnesium, zinc,
and iron absorption.
FOS or GOS 15 g/day for 3 weeks Healthy, nonanemic,
No significant effect on
calcium and iron
Short chain FOS 10 g/day for 5 weeks Healthy,
postmenopausal women
No significant effect on
calcium absorption. [200]
FOS enriched milk
5 g FOS/L with light breakfast
Healthy adults No significant effect on
calcium absorption. [201]
5 or 10 g per day for two 9
days with 19-day washout in
Calcium absorption
increased in a
dose-response way.
Trans-galacto-oligosaccharides 20 g for two 9 days with
19-day washout in between
Calcium absorption
increased. [203]
A mixed short and long
degree of polymerized
inulin-type fructan product
8 g/day for 8 weeks or 1 year Calcium absorption
increased significantly. [204]
The mixture of inulin +
8 g/day for two 3 weeks,
separated by a 2-week
washout period
Girls at or near
Calcium absorption
increased. [205]
7. Prebiotics Safety
Prebiotics are assumed to lack life-threatening or severe side effects. Intestinal enzymes cannot
break down oligosaccharides and polysaccharides. They are transported to the colon to be fermented
by the gut microbiota. Therefore, the side effects of prebiotics are mostly the result of their osmotic
functions. In this regard, osmotic diarrhea, bloating, cramping, and flatulence could be experienced in
prebiotic recipients. The prebiotics chain length is an influential parameter for the development of their
side effects. Interestingly, prebiotics with shorter chain length may have more side effects. The possible
explanation for this phenomenon is that shorter inulin molecules are metabolized primarily in the
proximal colon and are more rapidly fermented; whereas, longer chain ones are fermented later
and slower in the distal colon. Beside chain length, the prebiotic dose can affect its safety profile.
For example
, low (2.5–10 g/day) and high (40–50 g/day) doses of prebiotics can cause flatulence and
osmotic diarrhea, respectively. Noting that, a daily dose of 2.5–10 g prebiotics is required to exert their
beneficial functions on human health. This means that prebiotics within their therapeutic doses can
cause mild to moderate side effects. Most products of prebiotics in the market have doses of 1.5–5 g
per portion [206].
As potential alternatives or adjunctive therapies (synbiotics) to probiotics [
], prebiotics may
have similar safety concerns. The major safety issue of probiotics includes the risk of bacteremia, sepsis
or endocarditis, especially in patients with prominent immuno-deficiency (e.g., HIV, cancer, transplant),
severe malnutrition or incompetent intestinal epithelial barrier (e.g., severe diarrhea, NEC) [
]. It is
noteworthy that these potential complications have not been considered or at least reported in relevant
clinical studies exclusively for prebiotics.
8. Conclusions
Prebiotics exert a remarkable influence on human health, which makes them alluring attractive
agents to improve the quality of human life against cancer, vascular diseases, obesity, and mental
disorders. There are many studies on the positive effects of prebiotics on human health; however,
accurately designed long-term clinical trials and genomics investigations are needed to confirm the
health claims.
By determining the fundamental mechanisms of prebiotics, scientists would be able to formulate
enhanced food supplements to ameliorate human health. The ability to normalize the composition of
Foods 2019,8, 92 17 of 27
the gut microbiota by prebiotic dietary substances is an appealing procedure in the control and healing
of some foremost disorders. In other words, the gut microbiota, as a major body organ, can be fed
properly with prebiotics to become stronger and healthier, which, in turn, can impact the overall health.
Considering the diversity of the gut microbiota in various populations and countries, and even
in different individuals, based on the variety of dietary regimens, developing effective and diverse
probiotics for the modification of the microbiota hemostasis seems not to be very feasible. On the
other hand, prebiotics seem to be a more convenient option in this regard, especially due to a much
easier production and formulation process, as well as lack of need for cold chain in transportation and
storage. The negligible side effects of prebiotics are also an important advantage.
Therefore, designing particular, population-specific prebiotics with regard to the resident gut
microbiota specific to each community may ultimately contribute to the reduction of certain disorders
in each society as a standardized approach. This concept provides the potential to stop the huge
prebiotic controversies and can be recommended in future guidelines from the FAO and/or the WHO
on prebiotics.
Author Contributions: All authors have contributed to the manuscript preparation, review, and editing.
Funding: This study was supported by a Grant from Shiraz University of Medical Sciences, Shiraz, Iran.
Conflicts of Interest: The authors declare no conflict of interest.
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2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
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... Prebiotics are defined by the International Scientific Association for Probiotics and Prebiotics as "substrates that are selectively utilized by host microorganisms to confer health benefits to the host" (155). The two important groups of prebiotics are fructooligosaccharides (FOS) and galacto-oligosaccharides (GOS) (156). FOS is naturally present in asparagus, bananas, chicory root, garlic, and onion, as well as synthesized commercially (155,157); GOS is produced commercially from lactose by Bgalactosidase (156). ...
... The two important groups of prebiotics are fructooligosaccharides (FOS) and galacto-oligosaccharides (GOS) (156). FOS is naturally present in asparagus, bananas, chicory root, garlic, and onion, as well as synthesized commercially (155,157); GOS is produced commercially from lactose by Bgalactosidase (156). The effect of FOS and GOS on gut microbiota modulation has been shown previously (157). ...
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The gut microbiota is composed of a large number of microorganisms with a complex structure. It participates in the decomposition, digestion, and absorption of nutrients; promotes the development of the immune system; inhibits the colonization of pathogens; and thus modulates human health. In particular, the relationship between gut microbiota and gastrointestinal tumor progression has attracted widespread concern. It was found that the gut microbiota can influence gastrointestinal tumor progression in independent ways. Here, we focused on the distribution of gut microbiota in gastrointestinal tumors and further elaborated on the impact of gut microbiota metabolites, especially short-chain fatty acids, on colorectal cancer progression. Additionally, the effects of gut microbiota on gastrointestinal tumor therapy are outlined. Finally, we put forward the possible problems in gut microbiota and the gastrointestinal oncology field and the efforts we need to make.
... Prebiotics, a group of nutrients that can be degraded by gut microbiota, have been found to benefit probiotics and influence probiotics-related regulation [24]. As the products of prebiotics fermentation by gut microbiota were mainly acids, especially SCFAs, prebiotics could promote secretion of GLP-1 [25,26]. Moreover, the combination of probiotics and prebiotics has been demonstrated to have a better performance than probiotics or prebiotics alone on improving energy metabolism, immunity, and so on [27,28]. ...
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Type 2 diabetes (T2D) is a disease of global concern characterized by hyperglycemia and insulin resistance. Many studies found that glucagonlike peptide-1 (GLP-1) is an incretin hormone that can alleviate hyperglycemia and T2D. Recently, probiotics and their combination with prebiotics have been found to show great potentials of blood glucose regulation and T2D alleviation. Given the important role of GLP-1 in T2D, screening probiotics with the capacity of promoting GLP-1 secretion is of great help for providing a novel application of T2D treatment. In the current study, we evaluated the effects of three probiotics, namely, Lactobacillus paracasei LC-37 (LC-37), Bifidobacterium animals MN-Gup (MN-Gup), and Bifidobacterium longum BBMN68 (BBMN68), and their combination with prebiotics on promoting GLP-1 secretion using NCI-H716 cells. The results showed that LC-37 and MN-Gup could stimulate more GLP-1 secretion in NCI-H716 cells, but BBMN68 had no significant effect. Further evaluation suggested that the two combinations of LC-37 with isomaltooligosaccharide (IMO) and MN-Gup with galactooligosaccharide (GOS) had the best performance on promoting GLP-1 secretion in vitro. Subsequently, the effects of the two combinations on promoting GLP-1 secretion and alleviating T2D were investigated in vivo using high fat diet (HFD) and streptozotocin (STZ) treated rats. The results showed that the two combinations could significantly reduce fasting blood glucose levels, improve insulin resistance, and modulate serum lipid profiles in HFD/STZ-treated rats. These results will help understand the potential of promoting GLP-1 secretion of LC-37 and MN-Gup and provide theoretical basis for their applications in fermented milk or other foods.
... Some prebiotics, including FOS, inulin-type fructans, and galacto-oligosaccharides (GOS) were observed to exert beneficial effects by increasing the proportion of Bifidobacteria in the gut, especially in the context of a detrimental high fat diet that usually reduced the prevalence of these bacteria (Davani-Davari et al., 2019). Other carbohydrates, with prebiotic properties, such as arabinoxylans can also have a similar potential (Reis et al., 2014). ...
The human intestinal microbiota is composed of several types of microorganisms, including bacteria, archaea, fungi, unicellular eukaryotes and viruses. Among them, bacteria are the most diverse and abundant with a gene catalog 150 times larger than the genes present in the human genome, which represents a tremendous metabolic potential. These bacteria actively participate in the maintenance of intestinal homeostasis. Dysbiosis of the gut microbiota could be observed at course of many human pathologies, particularly inflammatory diseases intestinal chronic diseases (IBD), such as Crohn's disease (CD) or Ulcerative colitis (UC). These dysbiosis could contribute to the onset and progression of diseases. For example, gut microbiota transplantation experiments in murine model have allowed to show that a dysbiotic microbiota is sufficient to induce chronic inflammation in the colon and thus lead to the development of a metabolic syndrome or colitis. Different intervention strategies, including fecal transplantation, administration of probiotics or even special nutritional diets have been developed to act on the microbial communities of the digestive tract and to restore homeostasis of host tissues. The success of some interventions like Fecal transplantation represent a proof of concept in humans that acting on the composition of the intestinal microbiota is a strong lever to resolve certain physio pathological situations associated with gut microbiota dysbiosis. Diet is another important method for modulating the gut microbiota since it is the most important factor influencing its composition. In fact, the nutrients ingested can act directly on the composition of the microbiota by serving as substrates for microorganisms and indirectly by modulating intestinal homeostasis and components of the immune system associated, themselves contributing to regulate the composition microbiota. It is expected that ingestion of these beneficial microorga nisms can stimulate the immune system, promote intestinal homeostasis and to some extent contribute to the balance of the microbiota intestinal. The use of probiotic microorganisms is found to be very effective in some studies to treat different physiopathological situations (colitis, metabolic syndrome) in laboratory model organisms (rats, mice), however the use of these same probiotics in humans have given relatively disappointing clinical results, with poorly reproducible results across cohorts of patients. Except for the treatment of antibiotic-associated diarrhea. These discrepancies in results between pre-clinical models and clinical trials encourage better characterization of the molecular mechanisms used by probiotics to exert their beneficial effects and especially better understand the relationship of these probiotic microorganisms with the resident microbiota and diet.Among the different rising intervention strategies practiced nowadays in the purpose to shape the microbiota, a growing interest is given to other dietary interventions, like caloric restriction (CR) which has demonstrated several beneficial effects on various physiological systems, including the gastro-intestinal system, by modulating the innate and adaptative immune responses. In fact, emerging evidence suggests that the immune system function might be heavily influenced by the sensing of nutrient, reinforcing the idea that diet can deeply influence the inflammatory responses.
... However, due to costly pre-treatment technologies, one major constraint is the high cost of production. Bioethanol from first-generation feedstocks, on the other hand, is created from starch-and sugar-based feedstocks such as corn, wheat, and sugarcane, which are commonly used as human and livestock feed [5][6][7]. However, using food crops to produce bioethanol has resulted in an unbridgeable gap between energy and food security [1]. ...
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Concerns about first generation bioethanol's impact on the food chain and biodiversity have shifted research to second generation (2G) bioethanol technologies. The 2G-bioethanol is made from lignocellulosic biomass, which is more sustainable and does not harm food security or the environment. This production process uses non-food crops, food crop residues, wood or food wastes, such as wood chips, skins, or pulp from fruit pressing. The present study examines the bioethanol production potential of three lignocellulosic biomass residues: corn cob, corn husk, and corn stem, as well as their physiochemical and mineral composition before and after fermentation. Before fermentation, the corn waste samples were hydrolyzed into sugar monomer and the hydrolysate was fermented separately to produce bioethanol for five days at 282oC using two Saccharomyces cerevisiae strains: typed yeast ATCC 3585 and Baker's yeast ATCC 204508/S288c. At one-day intervals, the pH, simple sugar and ethanol production were measured. ANOVA was used to find significant differences between the investigated organisms. The results showed that Saccharomyces cerevisiae ATCC 35858 produces more ethanol than the other strain (20.25±0.63). Corn cob also produced more ethanol than stem and husk. During fermentation, the typed yeasts outperformed the Baker's yeast in pH, reducing sugar, and specific gravity. Average dry yeast cell mass (ADM) of Saccharomyces cerevisiae ATCC 35858 and Saccharomyces cerevisiae ATCC 204508/S288c were 1.82±0.07 and 1.98±0.03, respectively. According to proximate composition, fermentation lost over 50% of the corn waste's nutrients (ash), while recovering over 50% of the minerals (nitrogen, phosphorus, and potassium). The ability of the two Saccharomyces cerevisiae strains to produce bioethanol was not significantly different at p value ≤ 0.05.
... Prebiotics are indigestible carbohydrates by the host animal but can be utilized by useful GIT microorganisms (54,(141)(142)(143). Prebiotics are found in different food sources such as oats, barley, dandelion greens, chicory, chia seeds, flax seeds, onion, garlic, almonds, and artichoke (144). Green algae (Chlorophyta) are also considered prebiotic because of the presence of watersoluble sulfated polysaccharides; the perform gut microbiota modulation and immunomodulation, and they have antioxidant, antibacterial, anti-hyperlipidemia, and anti-diabetic properties (145). ...
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This article aimed to describe the current use scenario, alternative feed additives, modes of action and ameliorative effects in broiler production. Alternative feed additives have promising importance in broiler production due to the ban on the use of certain antibiotics. The most used antibiotic alternatives in broiler production are phytogenics, organic acids, prebiotics, probiotics, enzymes, and their derivatives. Antibiotic alternatives have been reported to increase feed intake, stimulate digestion, improve feed efficiency, increase growth performance, and reduce the incidence of diseases by modulating the intestinal microbiota and immune system, inhibiting pathogens, and improving intestinal integrity. Simply, the gut microbiota is the target to raise the health benefits and growth-promoting effects of feed additives on broilers. Therefore, naturally available feed additives are promising antibiotic alternatives for broilers. Then, summarizing the category, mode of action, and ameliorative effects of potential antibiotic alternatives on broiler production may provide more informed decisions for broiler nutritionists, researchers, feed manufacturers, and producers.
... The efficacy of probiotics increases profoundly with the addition of prebiotics to the diet. Prebiotics are the nondigestible fibres that increase the growth of the probiotics or the beneficial microorganisms in the intestine [14]. They remain undigested in the stomach and further move to the intestine where they get fermented or degraded by the probiotics and produce short chain fatty acids (SCFAs) like butyrate, propionate and acetate [15]. ...
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The increasing mortality due to hypertension and hypercholesterolemia is directly linked with type-2 diabetes. This shows the lethality of the disease. Reports suggest that the prebiotics along with probiotics help in lowering the effects of type-2 diabetes. Prebiotic like inulin is best known for its anti-diabetic effect. The current study utilizes jicama extract as prebiotic source of inulin along with the bacterial strains with probiotic properties (Lactiplantibacillus plantarum and Enterococcus faecium) for treating type-2 diabetes in high-fat diet-induced Drosophila melanogaster model. The high-fat diet-induced Drosophila showed deposition of lipid droplets and formation of micronuclei in the gut. The larva and adult treated with probiotics and synbiotic (probiotic + prebiotic- inulin) comparatively reduced the lipid deposition and micronuclei number in the gut. The increased amount of triglyceride in the whole body of the fatty larva and adult indicated the onset of diabetes. The overexpression of insulin-like genes (Dilp 2) and (Dilp 5) confirmed the insulin resistance, whereas the expression was reduced in the larva and adult supplemented with probiotics and synbiotic. The reactive oxygen species level was reduced with the supplementation of probiotics. The weight, larva size, crawling speed and climbing were also altered in high-fat diet-induced Drosophila melanogaster. The study confirmed the effects of probiotics and synbiotic in successfully lowering diabetes in Drosophila. The study also proved the anti-diabetic potential of the probiotics. Further, it was also confirmed that the probiotics work better in the presence of prebiotic. Graphical Abstract
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O CrossFit® é uma modalidade de treino de força que vem ganhando destaque no cenário nacional da Educação Física. O desempenho nos treinamentos depende da adesão e permanência dos participantes, que podem ser determinados por fatores motivacionais. Este estudo objetivou investigar quais são os fatores motivacionais de ingresso e permanência dos praticantes de CrossFi®. A pesquisa trata-se de um estudo de caráter transversal com natureza quantitativa, constituído por uma amostra de 198 (60,1% do sexo feminino) praticantes de CrossFi® dos boxes mais antigos da cidade de Fortaleza. Foi perguntado aos participantes do estudo quais os motivos de ingresso e permanência na prática do CrossFi®. Utilizou-se a estatística descritiva em frequência e percentual para análise dos resultados através do SPSS 21.0. Os resultados indicaram que a saúde é o principal fator de ingresso e permanência no CrossFi®. Concluiu-se que que os resultados aqui evidenciados possam ir além da contribuição científica e profissional, se estendendo para a sociedade, através de um melhor entendimento acerca dos fatores que estão envolvidos na aderência à prática de atividade física.
The health-promoting effects of probiotics include maintenance of normal intestinal microbiota, increased nutritional value of foods, and immune system stimulation. Multi-strain probiotics have recently been proposed as health-enhancing foods and functional food ingredients. Fruit-vegetable powders (FVP), being a kind of prebiotic, are food supplements that are non-digestible by the host, but can improve the host's health by selectively stimulating the growth or activities of gastrointestinal tract bacteria. However, the intestinal efficacy of multi-strain probiotics combined with FVP remains unclear. Therefore, the purpose of the present work was to explore the effect of multi-strain probiotics combined with FVP on intestinal inflammation. Lipopolysaccharide (LPS) was used to treat RAW264.7, which was then co-cultured with Caco-2 cells to mimic the intestinal inflammatory environment. Caco-2 cells were incubated with various probiotics and FVP (0.125 and 0.25 mg/mL). The inflammatory cytokines from the medium were collected for ELISA analysis, and the ZO-1 expression in the Caco-2 cells was examined by fluorescence assay. Probiotics combined with FVP significantly decreased the inflammatory cytokines, IL-6, and TNF-α, and increased ZO-1 expression when compared with the LPS only group. Probiotics combined with FVP could decrease inflammatory cytokines, and protect the intestinal barrier from tight junction dysregulation.
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Inulin is a popular prebiotic that is often used in the production of ice cream, mainly to improve its consistency. It also reduces the hardness of ice cream, as well as improving the ice cream’s organoleptic characteristics. Inulin can also improve the texture of sorbets, which are gaining popularity as an alternative to milk-based ice cream. Sorbets can be an excellent source of natural vitamins and antioxidants. The aim of this study was to evaluate the effect of the addition of inulin on the sensory characteristics and health-promoting value of avocado, kiwi, honey melon, yellow melon and mango sorbets. Three types of sorbets were made—two with inulin (2% and 5% wt.) and the other without—using fresh fruit with the addition of water, sucrose and lemon juice. Both the type of fruit and the addition of inulin influenced the sorbet mixture viscosity, the content of polyphenols, vitamin C, acidity, ability to scavenge free radicals using DPPH reagent, melting resistance, overrun and sensory evaluation of the tested sorbets (all p < 0.05). The addition of inulin had no impact on the color of the tested sorbets, only the type of fruit influenced this feature. In the sensory evaluation, the mango sorbets were rated the best and the avocado sorbets were rated the worst. Sorbets can be a good source of antioxidant compounds. The tested fruits sorbets had different levels of polyphenol content and the ability to scavenge free radicals. Kiwi sorbet had the highest antioxidant potential among the tested fruits. The obtained ability to catch free radicals and the content of polyphenols proved the beneficial effect of sorbets, particularly as a valuable source of antioxidants. The addition of inulin improved the meltability, which may indicate the effect of inulin on the consistency. Further research should focus on making sorbets only from natural ingredients and comparing their health-promoting quality with the ready-made sorbets that are available on the market, which are made from ready-made ice cream mixes.
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Dysbiosis of gut microbiota is closely related to occurrence of many important chronic inflammations-related diseases. So far the traditionally prescribed prebiotics and probiotics do not show significant impact on amelioration of these diseases in general. Thus the development of next generation prebiotics and probiotics designed to target specific diseases is urgently needed. In this review, we first make a brief introduction on current understandings of normal gut microbiota, microbiome, and their roles in homeostasis of mucosal immunity and gut integrity. Then, under the situation of microbiota dysbiosis, development of chronic inflammations in the intestine occurs, leading to leaky gut situation and systematic chronic inflammation in the host. These subsequently resulted in development of many important diseases such as obesity, type 2 diabetes mellitus, liver inflammations, and other diseases such as colorectal cancer (CRC), obesity-induced chronic kidney disease (CKD), the compromised lung immunity, and some on brain/neuro disorders. The strategy used to optimally implant the effective prebiotics, probiotics and the derived postbiotics for amelioration of the diseases is presented. While the effectiveness of these agents seems promising, additional studies are needed to establish recommendations for most clinical settings.
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Prebiotic dietary fibers act as carbon sources for primary and secondary fermentation pathways in the colon, and support digestive health in many ways. Fructooligosaccharides, inulin, and galactooligosaccharides are universally agreed-upon prebiotics. The objective of this paper is to summarize the 8 most prominent health benefits of prebiotic dietary fibers that are due to their fermentability by colonic microbiota, as well as summarize the 8 categories of prebiotic dietary fibers that support these health benefits. Although not all categories exhibit similar effects in human studies, all of these categories promote digestive health due to their fermentability. Scientific and regulatory definitions of prebiotics differ greatly, although health benefits of these compounds are uniformly agreed upon to be due to their fermentability by gut microbiota. Scientific evidence suggests that 8 categories of compounds all exhibit health benefits related to their metabolism by colonic taxa.
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The emergence of antibiotic-resistant and food-spoilage microorganisms has renewed efforts to identify safe and natural alternative agents of antibiotics such as probiotics. The aim of this study was the isolation of lactobacilli as potential probiotics from local dairy products with broad antibacterial and anti-biofilm activities against antibiotic-resistant strains of Pseudomonas aeruginosa and determination of their inhibition mechanism. Antibiotic susceptibility and classification of acquired resistance profiles of 80 P. aeruginosa strains were determined based on Centers for Disease Control and Prevention (CDC) new definition as multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) followed by antibacterial assessment of lactobacilli against them by different methods. Among the 80 P. aeruginosa strains, 1 (1.3%), 50 (62.5%), and 78 (97.5%) were PDR, XDR, and MDR, respectively, and effective antibiotics against them were fosfomycin and polymyxins. Among 57 isolated lactobacillus strains, two strains which were identified as Lactobacillus fermentum using biochemical and 16S rDNA methods showed broad inhibition/killing and anti-biofilm effects against all P. aeruginosa strains. They formed strong biofilms and had bile salts and low pH tolerance. Although investigation of inhibition mechanism of these strains showed no bacteriocin production, results obtained by high-performance liquid chromatography (HPLC) analysis indicated that their inhibitory effect was the result of production of three main organic acids including lactic acid, acetic acid, and formic acid. Considering the broad activity of these two L. fermentum strains, they can potentially be used in bio-control of drug-resistant strains of P. aeruginosa.
In 1995, Gibson and Roberfroid defined a prebiotic as a “nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limitednumber of bacteria in the colon, and thus improves host health.” This definition only considers microbial changes in the human colonic ecosystem. Later, itwas considered timely to extrapolate this into other areas that may benefit from a selective targeting of particular microorganisms and to propose a refined definition of a prebiotic as (Gibson et al. 2004): a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinalmicrofiora that confers benefits.
Fermentation by lactic acid bacteria, molds and yeasts is one of the oldest methods for a safe preservation of foods. Many probiotics are a natural part of the beneficial gut microbiota and have a 'generally recognized as safe' (GRAS) status. Prebiotic carbohydrates such as inulin and fructooligosaccharides (FOS) are natural vegetable components and considered as GRAS. Cases of adverse effects of probiotics are very rare and occur nearly exclusively in severely ill or immune compromised individuals. For prebiotics an eventual inconvenience is gas production in the gut. Possibilities to utilize probiotics to increase the safety in foods and drinking water are addressed.