Fructooligosaccharides - type prebiotic : A Review

Abstract

The main advantage of prebiotic oligosaccharides is that they are natural functional ingredients. Prebiotics are being used in the food industry as functional ingredients in beverages, milk products, probiotic yogurts and symbiotic products. Fructooligosaccharides (FOS) are oligosaccharides that occur naturally in Medicinal plants such as onion, chicory, garlic, asparagus, banana, artichoke, among many others. FOS are not digested by the human gastrointestinal tract, and when they reach the colon, they beneficially stimulate the growth and strengthening of specific bacteria in the intestine. Several studies have demonstrated the functional properties of FOS, such as the reduction of cholesterol levels and blood glucose levels, lowering of blood pressure, better absorption of calcium and magnesium and to inhibit production of the reductase enzymes that can contribute to cancer. Currently FOS are increasingly included in food products and infant formulas due to their prebiotic effect stimulate the growth of nonpathogenic (bifidobacteria) intestinal microflora and decreases growth of potentially pathogenic bugs and enhances the immune system.

Full text

Journal of Pharmacy Research Vol.8 Issue 3.March 2014
V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330
321-330
Review Article
ISSN: 0974-6943 Available online through
www.jpronline.info
*Corresponding author.
Dr. M. Satish Kumar,
Associate Professor,
Vidya Vikas Institute of Engineering and Technology,
Visvesvaraya Technological University,
Alanahalli,
Mysore – 570028. Karnataka. ,India.
Fructooligosaccharides - type prebiotic : A Review
V. Sridevi+, V. Sumathi#, M. Guru Prasad*§ and Satish Kumar.M. *§¶
+ Department of Biotechnology, Sri Venkateswara University,Tirupati - 517 502, A.P,India.
# Department of Biotechnology, Sri Padmavati Mahila Visva Vidyalayam,Tirupati - 517 502, A.P,India.
* Department of Biochemistry, Bharathiyar University, Coimbatore - 641046, T.N. ,India.
§ Vidya Vikas Institute of Engineering & Technology, Alanahalli, Mysore 570028. Karnataka. ,India.
¶ Department of Chemistry, P.E.S.College Of Engineering, Mandya - 571401, Karnataka. ,India.
Received on:12-01-2014; Revised on: 06-02-2014; Accepted on:18-02-2014
ABSTRACT
The main advantage of prebiotic oligosaccharides is that they are natural functional ingredients. Prebiotics are being used in the food
industry as functional ingredients in beverages, milk products, probiotic yogurts and symbiotic products. Fructooligosaccharides (FOS) are
oligosaccharides that occur naturally in Medicinal plants such as onion, chicory, garlic, asparagus, banana, artichoke, among many others.
FOS are not digested by the human gastrointestinal tract, and when they reach the colon, they beneficially stimulate the growth and
strengthening of specific bacteria in the intestine. Several studies have demonstrated the functional properties of FOS, such as the reduction
of cholesterol levels and blood glucose levels, lowering of blood pressure, better absorption of calcium and magnesium and to inhibit
production of the reductase enzymes that can contribute to cancer. Currently FOS are increasingly included in food products and infant
formulas due to their prebiotic effect stimulate the growth of nonpathogenic (bifidobacteria) intestinal microflora and decreases growth of
potentially pathogenic bugs and enhances the immune system.
Key words: Biomedical and industrial importance, Fructooligosaccharides, Prebiotics
INTRODUCTION:
Prebiotics are generally defined as non-digestible polysaccharides
and oligosaccharides (NDO), which promote the growth of beneficial
lactic acid bacteria in the colon and exert antagonism to Salmonella
sp. or Escherichia coli, limiting their proliferation. The term prebiotics
was coined by Gibson and Roberfroid1. Gibson et al.,2 elaborated the
prebiotics concept by certain criteria viz. resistance to gastric acidity,
hydrolysis by mammalian enzymes and gastrointestinal absorption;
fermentation by intestinal microflora and selective stimulation of the
growth, and/or activity of intestinal bacteria associated with health
and wellbeing. There exists an array of prebiotics with various origin
and chemical properties. In particular, many food oligosaccharides
and polysaccharides (including dietary fiber) have been claimed to
have prebiotic activity, but not all dietary carbohydrates are prebiotics.
Gibson and colleagues2 have reviewed their original prebiotic con-
cept in the light of much research that has been published in the past
decade, and in particular the three key aspects of their definition: (1)
resistance to digestion; (2) fermentation by the intestinal microflora;
and (3) a selective effect on the flora that promote health. Their up-
dated definition is: “A prebiotic is a selectively fermented ingredient
that allows specific changes, both in the composition and/or activity
in the gastrointestinal microflora that confers benefits upon host well-
being and health”. The key words in both definitions are “selective”
and “benefit/improve...host...health”. Therefore, a prebiotic substrate
must be particularly readily available to some groups of bacteria of
which lactobacilli and bifidobacteria are considered indicator organ-
The principal concept associated with both of these definitions is
that the prebiotic has a selective effect on the intestinal microbiota
which results in an improvement in health of the host. The definitions
arose from observations that particular dietary prebiotics as func-
tional ingredients bring about a specific modulation of the GI ecosys-
tem, particularly increased numbers of beneficial bacteria, and de-
creased numbers of potential pathogenic species, which associated
with improved host health. These are not absorbed in small intestine
isms that are beneficial to intestinal health, but less available to po-
tentially pathogenic bacteria, such as toxin-producing Clostridia,
proteolytic Bacteroides and toxygenic E. coli3. In this manner, a
“healthier” microbiota composition is obtained whereby the
bifidobacteria and/or lactobacilli become predominant in the intestine
and exert possible health promoting effects.

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major determining factor in whether to purchase a food item. The
food industry has invested in some great innovations, mainly in the
formulation of ingredients and additives, functional foods, transgenic
foods and packaging22. The increased demand for functional foods in
recent years is closely related to the growing concern of society with
health and quality of life. Moreover, consumers are more informed
and aware about the foods that can benefit health. Prebiotic are in-
creasingly added to foods for their health benefits. Several industrial
products containing added prebiotics can be found in the consumer
market: dairy products, breads, fruit juices, margarine, pasta, dairy
desserts, ice creams, cereals, milk, yogurt, biscuits, soft drinks in
general, isotonic drinks, liquid sugar and modified sugar, chocolates
and candies in general.
In prebiotic studies, fructooligosaccharides -type prebiotics have
been studied as an isolated intervention in field of health concern.
This review focuses on the beneficial effect on human concern; how-
ever, a summary fructooligosaccharides prebiotic research is pro-
vided.
Fructooligosaccharides (FOS)
Several studies have demonstrated the functional properties of
fructooligosaccharides (FOS), such as the reduction of cholesterol
levels and blood glucose levels, lowering of blood pressure, better
absorption of calcium and magnesium and to inhibit production of
the reductase enzymes that can contribute to cancer23,24. FOS are not
digested by the human gastrointestinal tract, and when they reach
the colon, they beneficially stimulate the growth and strengthening
of specific bacteria in the intestine12. The bifidobacteria secrete ß-
fructosidase, which would be the enzyme responsible for FOS hy-
drolysis25. The average counts of bifidobacteria increased, whereas
there were significant reductions in Bacteroides, Fusobacteriumand
Clostridium sp.
Structure:
Their chemical structure consists of a chain of fructose units with
a terminal glucose unit linked by ß(3-(2-1) glycosidic bonds, which
means they cannot be hydrolysed by human digestive enzymes
which are specific for a glycosidic bonds. The length of the chain
ranges from 2 m 60. There are three categories of FOS, each of which
is structurally distinct: inulin, has a polymerization degree of 2 to
about 60 monomers of fructose, with an average of 12 units (57):
oligofrumose is produced by the enzymatic hydrolysis of inulin
and is defined as a fraction of oligosaccharides with degree of poly-
merization lower than 20, although commercial products tend to
have a mean value of 9; these FOS are produced by the enzymatic
hydrolysis of inulin and consists of frucrosyl chains of different
lengths, with glucose and fructose terminals. Finally, scFOS (short
chain fructooligosaccharides) are specifically defined as mixed chains
of fructosyl with a glucose terminal unit; they have a maximum of 5
units and are derived from sugar through natural fermentation pro-
cesses, producing 1-kestose (CF 2), nistose (CF 3) and 1-fructosyl
- nistose (GF 4) in which the fructosyl units (F) are linked at ß-(2-1)
position of sucrose (Fig1).
of healthy individuals but later are fermented by natural microflora of
the colon to produce short-chain fatty acids (SCHFA)4. The main
advantage of prebiotic oligosaccharides is that they are natural func-
tional ingredients. Their incorporation in the diet does not require
particular precautions, and their authorization as food/feed additives
may be more easily obtained, in spite of some concerns about their
safety and efficacy5. Stowell6 reviewed the existing prebiotics and
classified them based on a set of common criteria. Inulin,
fructooligosaccharides (FOS), galactooligosaccharides (GOS),
lactulose and polydextose are recognized as the established
prebiotics, whereas isomaltooligosaccharides (IMO),
xylooligosaccahrides (XOS), and lactitol are categorized as emerging
prebiotics. Chicory root inulin-derived (FOS), wheat bran-derived
arabinoxylooligosaccharides (AXOS) and xylooligosaccharides (XOS)
proved to have huge applications7-9. Prebiotics can be found in some
vegetables, such as leeks, onions, chicory, tomatoes, asparagus, arti-
chokes, bananas, and alfalfa. It can also be added to industrial prod-
ucts such as foods for children, dairy and confectionery products,
beverages, light mayonnaise and low-fat cheese, and they can be
used as dietary supplements10,11.
Prebiotics are being used in the food industry as functional ingredi-
ents in beverages (fruit juices, coffee, cocoa, tea, soft drinks and
alcoholic beverages), milk products (fermented milk, milk powder and
ice cream), probiotic yogurts and symbiotic products12,13 . Other ap-
plications include desserts (e.g., jellies, puddings, fruit-flavored ice
cream), confectionery items (e.g., sweets), biscuits, breakfast cereals,
chocolates, breads and pastas, meat products (e.g., fish paste) and
tofu. Prebiotics can also be used in cosmetics, pharmaceuticals and
products for people with diabetes13.
Prebiotics may exhibit the following properties:
•Maintenance of intestinal flora and stimulation of intestinal
transit11;
•Change in colonic microflora, contributing to normal stool
consistency, preventing diarrhea and constipation14-16;
•Elimination of excess substances such as glucose and cho-
lesterol, favoring only the absorption of substances
needed17;
•Stimulation of the growth of bifidobacteria18;
•Stimulation of the absorption and production of B vitamins
(B1, B2, B3, B6, B9, B12)19;
•Support of the immune system20;
•Contribution to the control of obesity21; and
•Contribution to the decrease of the risk of osteoporosis17
Due to poor nutrition, tobacco and alcohol consumption, the past
few decades have seen alarming increase in morbidity and mortality.
With instances of chronic obesity, gastrointestinal disorders, diabe-
tes, coronary diseases, cancers, and degenerative diseases on the
rise, growing numbers of consumers are looking up to companies
manufacturing prebiotics. Cashing in on the consumer craze for low-
carbohydrate high-fiber diet, nutraceutical market is being dominated
by a wide range of prebiotic products. The health effect of food is a

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Fig.1 Chemical structure of short chain fructooligosaccharides
Fructooligosaccharides (FOS) belong to the group of oligosaccha-
rides and are isolated from plants. In the extraction commercialization
process, FOS can be obtained from inulin by means of the
transfructosylation enzymatic reaction in sucrose residues by the
action of the ß-fructofuranosidase enzyme, with the DP of these prod-
ucts varying between 1 and 7 fructosyl units26.
Requirement:
Flamm et al.,27 have evaluated the caloric value of FOS and found that
the energy yield for the host would be in the range of 1.5 kcal/g to 2.0
kcal/g. By using another method based on lipogenesis balance,
Roberfroid28 stated that the caloric value of FOS is around 1.0 kcal/g
to 1.5 kcal/g. In Holland, it is estimated that the consumption of FOS
is 2 g to 12 g per day. In Japan, the estimate is between 13.7 mg/kg of
body weight per day. However, for the approval of FOS, the Japanese
law established the amount of 0.8 g/kg of body weight per day as an
acceptable daily intake29,30. The average per capita daily consump-
tion of FOS is 2 - 4 g for North Americans and 2 - 12 g for Europeans31.
In Brazil, there are no relevant data regarding the amount consumed
or the dietary recommendations. The law considers FOS as ingredi-
ents of products, not additives. FOS are considered as dietary fiber,
and in the United States, they have a GRAS status (Generally Recog-
nized As Safe). Ingestion may cause flatulence, especially in indi-
viduals who have lactose intolerance, but the severity of this symp-
tom is associated with the amount of FOS consumed: the higher the
quantity, the greater the symptom32. The intake of 20 g to 30 g per day
can promote severe discomfort in an individual, and thus, the optimal
intake level is 10 g per day30. For the promotion of colon floral bal-
ance, the amount of FOS needed has been determined to be 2 g to 2.5
g per day33. The minimum dose of FOS for the induction of diarrhea is
44 g for men and 49 g for women34, 35. For enteral nutrition, several
clinical studies suggest the amount of 5 - 10 g/day for the mainte-
nance of normal flora and from 12.5 g/day to 20.0 g/day for
bifidobacteria recovery36. In vitro and in vivo studies have suggested
the lack of genotoxicity and mutagenicity of FOS. Evaluations con-
ducted in rats showed no adverse effects with quantities lower than
2.17 g/kg/day34, 37.
Source:
FOS are available in some foods such as bananas, garlic, onion, to-
mato, wheat, asparagus, artichoke, leek, honey, rye, brown sugar,
barley, triticale, beer, lettuce, chicory, burdock, beetroot, apples, bulbs
like red lilies, yacon and oats, with onion being the food with the
highest levels of FOS (Table 1).
Table 1. Amount of FOS (%) per 100g raw in some natural foods.
Food Percentage
Chicory root 22.9 g
Jerusalem artichoke 13.5 g
Dandelion greens 10.8 g
Garlic 5 g
Leek 5.2 g
Asparagus 2.5 g
Banana 0.5 g
Production:
After extraction of native inulin, the product then undergoes either
industrial physical separation of long-chain fructans38 or is partially
hydrolyzed by endoinulinase to produce short-chain oligosaccha-
rides, mainly oligofructose (Fig. 2). Oligofructose produced from inu-
lin may or may not have a terminating glucose molecule, may contain
longer-chain fructans39 , and has a DP of 2–10 (average 5)40. Alterna-
tively, short-chain fructooligosaccharides can be produced syntheti-
cally through transfructosylation of sucrose using the b -
1-Kestose Nystose 1 Fructofuranosyl Nystose

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fructofuranosidase enzyme39 from Aureobasidium pullulans or As-
pergillus niger41 . These compounds contain 2–4 fructosyl units
with a terminal glucose unit and an average DP of 3.540. Synthetic
fructooligosaccharides contain only Gpy Fn oligomers. These prod-
ucts may contain free glucose, fructose, and sucrose, which can be
removed via chromatographic procedures to increase the purity of
the fi nal product. It should be noted, however, that a large amount of
starting material is needed to achieve efficient transglycosylation41.
Fructans are perhaps the most well-established prebiotics42 and the
most extensively studied. They meet the three key criteria defi ning a
prebiotic, that inulin-type fructans are nondigestible43, are fermented
in the large bowel, and lead to selective growth of bacteria associated
with health in vitro44 and in vivo [human subjects, including infants45,
adults 46 and the elderly47.
Mode of action:
The mechanism by which the inhibition of pathogens occurs (exog-
enous or endogenous) can be explained by the lowering of the pH in
the intestinal lumen as a consequence of the formation of short chain
fatty acids (SCFA) by FOS fermentation19,25. The decrease in the num-
ber of harmful bacteria (such as Escherichia coli, Clostridium, Strep-
tococcus faecallis and Proteus) results in the decrease in toxic me-
tabolites, such as ammonia, indoles, phenols and nitrosamines48.
Modler49 verified that adding NeosugarR (a trade name of
fructooligosaccharides) to the human diet (15 g/day) caused a ten-
fold increase in the population of bifidobacteria in the large intestine,
as well as increasing the occurrence of bifidobacteria from 87% to
100%. Concomitantly, there was a reduction of 0.3 intestinal pH units
and a decrease in the enterobacteria count. Hidaka et al.,50 found that
Fig.2 Commercial production of fructooligosaccharides from extracts of natural sources
the administration of 8 g/day of Neosugar in the human diet increased
the production of fatty acids. Wang and Gibson51 found the follow-
ing benefits could be attributed to bifidobacteria: they are
immunomodulatory against malignant cells, produce B vitamins and
folic acid, stimulate the production of digestive enzymes and lysozyme
and restore normal intestinal biota after antibiotic therapy. Regarding
the bifidogenic dose of FOS, authors like Roberfroid et al52 estab-
lished that about 4 g per day would be enough for an adult. Bouhnik53
demonstrated that FOS ingestion at doses of 12.5 g/day for three
days (clinically tolerated dose) produced a decrease in the total count
of anaerobes in the feces, in pH, in the activity of nitroreductase, in
bile acid concentrations and in serum levels of total cholesterol and
lipids.
Beneficial Health Effects
Infant Health:
Exclusive breastfeeding is strongly recommended for newborn in-
fants with a family history of allergy, as breastfeeding reduces the
likelihood that the infant will develop atopic disease. One study in
infants directly evaluated whether infant formula supplementation
with prebiotics could replicate the protective effect of breastfeeding.
In this study, 259 infants at risk for atopic disease were randomized to
receive either control formula or formula supplemented with a blend
of FOS (9:1 ratio; 8 g/L)54. Fecal microbiota were analyzed in a sub-
group of 98 infants. Levels of bifidobacteria were significantly higher
among infants who received the prebiotics compared to control in-
fants; levels of lactobacilli did not differ between the groups. Over
the 6 month course of the study, fewer infants in the supplemented
group developed atopic dermatitis compared to the control group,

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suggesting that prebiotics may modulate postnatal immune develop-
ment in part by altering the GI microbiota; there may be other mecha-
nisms as well. This study supports a potentially positive role for
prebiotics in managing symptoms of allergy during infancy, but addi-
tional studies are still needed. One clinical study in children sug-
gested that supplementation with FOS (2 g/d) for 21 days could im-
prove their immunological status, based on a lower incidence of fe-
ver, vomiting, and diarrhea in those taking the supplement55.
Another study, conducted among breastfed infants living in a com-
munity near Lima, Peru with a high prevalence of GI and other infec-
tions, found that feeding infant cereal supplemented with oligofructose
at 0.55 g/15 g cereal for 6 months was not associated with change in
incidence of diarrhea, use of health care resources, or response to a fl
u vaccination. A high prevalence of breastfeeding in the study popu-
lation was thought to contribute to the lack of effect with prebiotics
observed56. Further studies in infants and children are needed to
clarify these findings.
A randomized, placebo-controlled trial, involving 134 infants less than
6 months old whose parents suffered from allergies, found that those
fed a prebiotic combination of FOS/GOS experienced a significant
reduction in both allergy symptoms and minor infections that lasted
at least through age 2. The researchers suggested that the favorable
effects of prebiotics on intestinal bacteria early in life may produce
lasting benefits to the immune system57. One study found that use of
inulin promoted growth of probiotic bacteria in the bifidobacteria
family58.
Immune boosters:
Studies of Babu et al.,59 confirmed that FOS has an anti inflammatory
effect in chickens. This study, Salmonella Enteritidis (SE) is used as
test organism and it is one of the leading causes of food-borne salmo-
nellosis, and macrophages play an essential role in eliminating this
pathogen. They study on tested the influence of a prebiotic
fructooligosaccharide (FOS)-inulin on the ability of the chicken mac-
rophage HD11 cell line to phagocytose and kill SE, and express se-
lected inflammatory cytokines and chemokines in an in vitro model.
There were significantly fewer viable intracellular SE in HD11 cells
treated with FOS-inulin than the untreated cells. However, SE phago-
cytosis, nitric oxide expression or production were not influenced by
the prebiotic treatment. Among the inflammatory markers tested, IL-
1ß expression was significantly lower in HD11 cells treated with FOS-
inulin. These results suggest that FOS-inulin has the ability to modu-
late the innate immune system as shown by the enhanced killing of
SE and decreased inflammasome activation.
Yancui Zhao et al.,60 studied the effects of probiotic Bacillus TC22
(isolated from intestine of infected sea cucumber) and prebiotic
fructooligosaccharide (FOS) on growth, immunity and disease resis-
tance in sea cucumberApostichopus japonicas. Six experimental di-
ets were formulated with combinations of three levels of TC22 (0,
107 and 109 CFU g-1 diet) and two levels of FOS (0 and 0.5%) in a 3 × 2
factorial experiment. At the end of the 8-week feeding trial, animals
were challenged by injecting Vibrio splendidus. The results revealed
that the specific growth rates (SGR) of sea cucumbers were not af-
fected by TC22 and FOS, or the interaction between TC22 and FOS
(P > 0.05). However, there were significant interactions between TC22
and FOS for immune response and disease resistance in sea cucum-
bers (P < 0.05). When sea cucumbers were fed with TC22 at 109 CFU
g-1 feed and 0.5% FOS alone or in combination, the phagocytosis,
respiratory burst and phenoloxidase activity of sea cucumber
coelomocytes were significantly enhanced; the disease resistance
against V. splendidusinfection was also increased significantly. This
study confirms FOS involved in boosting up of immunity and disease
resistance of sea cucumbers.
Vos et al.,61 studied the the immunemodulatory effect of specific pre-
biotic oligosaccharides viz. GOS, FOS and pectin-derived acidic oli-
gosaccharides. The supplementation exerted immunemodulatory ef-
fect during the early phase of a murine immune response. Prebiotics
may reduce the incidence of degenerative diseases, such as neoplasias,
diabetes, coronary diseases and infections. They also seem to pro-
mote a positive modulation of the immune system62. Stam et al., 63
conducted a RCT on the effect of a prebiotic mixture supplementation
in formula food on the antibody responses to Influenza and tetanus
vaccination in infants during the first year of life. It was hypothesized
that a prebiotic mixture of short-chain GOS, long-chain FOS and pec-
tin-derived acidic oligosaccharides, resembling the composition of
oligosaccharides in human milk, promote T Helper 1 (Th1) and regu-
latory T cell (Treg)-dependent immune responses and induce down
regulation of IgE mediated allergic responses. Additionally, the prebi-
otic administration does not interfere with the desired vaccinespecific
serum antibody responses in healthy term infants63.
Improve mineral absorption:
A naturally sweet, indigestible fiber derived from chicory roots, FOS
(fructooligosaccharides) are one of the best-documented, natural
nutrients for promoting the growth of Lactobacilli and bifidobacteria
bacteria, a key to sound health. FOS has also been clinically studied
for its ability to increase magnesium and calcium absorption. Be-
cause FOS can increase magnesium absorption, it can also lead to
lowered blood pressure and better cardiovascular health. FOS is one
of the most powerful prebiotics to be researched in the last decade (a
“prebiotic” feeds intestinal flora; a “probiotic” adds more actual cul-
tures to existing intestinal flora). The subject of over 100 clinical stud-
ies, FOS is one of the best-documented natural nutrients for improv-
ing the healthy balance of bacteria in intestines and stimulating the
growth of the beneficial bifidobacteria also called “friendly flora” that
reside in the colon.
Besides building up the beneficial bacteria in the body, FOS has also
been shown to improve blood sugar control, liver function, and cal-
cium and magnesium absorption. A 1997 animal study conducted at
the Nutritional Research Center in Japan found that a 5 percent FOS
diet increased magnesium and calcium absorption substantially. A
1998 Showa University study, obtained similar results64, 65. Magne-
sium is one of the most important nutrients we obtain from our diet,

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being involved in over 300 enzyme reactions in the body. As we age,
our magnesium levels drop markedly, which creates a deficiency that
increases the risk of angina, atherosclerosis, cardiac arrhythmias,
depression, and diabetes66. A study conducted by National Research
Council of Canada showed that long-term marginal magnesium defi-
ciency can reduce the life span of laboratory animals by almost 40
percent67.
Small double-blind studies found that FOS at a dose of 10 g daily may
improve magnesium absorption in postmenopausal women.68Whether
this is beneficial remains unclear, since magnesium deficiency is not
believed to be a widespread problem. FOS may also slightly increase
copper absorption , but does not appear to affect absorption
of calcium , zinc , or selenium69,70.
Reduction of cholesterol levels:
Animal studies hint that FOS, GOS, and inulin can significantly
improve cholesterol profile; however, study outcomes in humans have
been inconsistent at best.71-77. One study found that while inulin might
produce a short-term benefit, any such benefit disappears after six
months of use.78 At most, it appears that FOS might improve choles-
terol profiles by 5%, an amount too small to make much of a difference
in most circumstances. These relatively poor results might be due to
that fact that humans cannot tolerate doses of FOS much above 15 g
daily without developing gastrointestinal side effects.
Diarrhea
FOS has also been suggested for preventing traveler’s diarrhea .
However, in a large (244-participant) double-blind study, FOS at a
dose of 10 g daily again offered only minimal benefits79.
Probiotics themselves might be a better bet. Another study found
that use of FOS might help reduce incidents of diarrhea, flatulence,
and vomiting in preschoolers80.
Type 2 diabetes
According to most studies, FOS at 10-20 g daily do not improve
blood sugar control in people with type 2 diabetes81,82. In a prelimi-
nary trial, supplementation with fructo-oligosaccharides (FOS) (8
grams per day for two weeks) significantly lowered fasting blood-
sugar levels and serum total-cholesterol levels in people with type 2
diabetes79. However, in another trial, supplementing with FOS (15
grams per day) for 20 days had no effect on blood-glucose or lipid
levels in people with type 2 diabetes83. In addition, some double-
blind trials showed that supplementing with FOS or galacto-oligosac-
charides (GOS) for eight weeks had no effect on blood-sugar levels,
insulin secretion, or blood lipids in healthy people84,85. Because of
these conflicting results, more research is needed to determine the
effect of FOS on diabetes and lipid levels.
Bowel syndrome:
FOS have been advocated as a treatment for irritable bowel syndrome .
However, research results are currently inconsistent at best. For ex-
ample, a 6-week, double-blind study of 105 people with mild irritable
bowel syndrome compared 5 g of fructo-oligosaccharides daily against
placebo, and returned conflicting results83. According to some mea-
sures of symptom severity employed by the researchers, use of FOS
led to an improvement in symptoms. However, according to other
measures, FOS actually worsened symptoms. Conflicting results,
though of a different kind, were also seen in a 12-week, double-blind,
placebo-controlled study of 98 people86. Treatment with FOS at a
dose of 20 g daily initially worsened symptoms, but over time this
negative effect wore off. At no time in the study were clear benefits
seen, however. On a positive note, one study did find benefit with a
combination prebiotic-probiotic formula84, and another study found
the combination beneficial for women with constipation when taken
in yogurt 87.
Cancer studies
Fabrice et al.,88 studied effect of short chain FOS on colon cancer,
which might reduced the occurrence of colon tumors and developed
gut-associated lymphoid tissue in min mice. This study shown that
sc-FOSs did not reduce the occurrence of tumors in the small intes-
tine96, immunosurveillance was specifically generated in the colon
and implicated the local immune system. As most ?,d-receptor-bear-
ing intraepithelial lymphocytes are CD4– CD8– (11) and thus not af-
fected by depletion, it is unlikely that these cells were the main effec-
tor subset. Immunosurveillance appeared to be specifically gener-
ated by the diet since the Min phenotype was independent of the
immune system, as shown by Dove et al.,89 and Dudley et al., 90. This
study shows that sc-FOSs may provide an immunocompetent host
with a mechanism of tumor surveillance, operative against spontane-
ously arising colon tumors.
Endogenous or exogenous bile acids, as well as dietary cholesterol
are carcinogenic factors involved in colon cancer in laboratory ani-
mals92,93. Various epidemiological studies suggest those steroids could
also be involved in colon cancer in men94,95. According to these stud-
ies, low scFOS dose ingestion by humans, which prevented microbial
conversion of cholesterol into cytotoxic molecule, (coprostanol, po-
tentially carcinogenetic), could be interesting for humans. In Yoram
Bouhnik et al.,96 study, the intake of 8 g/d scFOS led to increasing
faecal cholesterol. The mechanism of such increase could be related
to decreasing cholesterol bacterial transformation, although failed to
find any significant sc-FOS effect on cholesterol bacterial metabo-
lism. Moreover, the low scFOS dose used in this study was also
probably not sufficient to significantly reduce microbial conversion
of bile acids, which is commonly increased in elderly living in
industrialised countries and they found significant change in choles-
terol metabolism, which could potentially exert protective action
against colon cancer.
Safety Issues
FOS appear to be generally safe. However, they can cause bloating,
flatulence, and intestinal discomfort, especially when taken at doses
of 15 g or higher daily. 6,7 People with lactose intolerance may par-
ticularly suffer from these side effects97.
CONCLUSIONS:
Several studies have demonstrated the functional properties of

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321-330
fructooligosaccharides (FOS), such as the reduction of cholesterol
levels and blood glucose levels, lowering of blood pressure, better
absorption of calcium and magnesium and to inhibit production of
the reductase enzymes that can contribute to cancer. FOS is used to
improve dysbiosis by enhancing growth of bifidobacteria, decreases
growth of potentially pathogenic bugs and enhances the immune
system. Demand of FOS, there might have the need of genetically
engineering plants for the production of FOS has also become more
prevalent, despite the still limited insight into the immunological
mechanisms activated by such food supplementation.
REFERENCES:
1. Gibson GR, Roberfroid MB, Dietary modulation of the human
colonic microbiota: Introducing the concept of prebiotics.
JNutrition 125,1995,1401-1412.
2. Gibson GR, Probert H M, Van Loo J, Rastall RA., Roberfroid
MB, Dietary modulation of the human colonic microbiota:
Updating the concept of prebiotics. Nutrition Research Re-
views 17,2004,259-275.
3. Manning TS, Gibson GR, Prebiotics Best Practice Res Clinic
Gastroenterology 18(2),2004,287-298.
4. Vaidya RH, Sheth MK, Processing and storage of Indian
cereal and cereal products alters its resistant starch content.
J Food Sci Technol 48, 2010, 622–627.
5. Gatesoupe FJ, Probiotics and prebiotics for fish culture, at
the parting of the ways. Aqua Feeds: Formulation Beyond
2(3), 2005, 3-5.
6. Stowell J Chapter 4. Calorie control and weight manage-
ment. In: Mitchell H (ed) Sweeteners and sugar alternatives
in food technology. Blackwell Publishing Ltd. doi:10.1002/
978047099 6003.ch4,2007.
7. Sabater-Molina M, Larque E, Torrella F, Zamora S, Dietary
fructooligosaccharides and potential benefits on health. J
Physiol Biochem 65, 2009, 315–328
8. Femia AP, Salvadori M, Broekaert WF, Francois IEJA,
Delcour JA, Arabinoxylan-oligosaccharides (AXOS) reduce
preneoplastic lesions in the colon of rats treated with 1,2-
dimethylhydrazine (DMH). Eur J Nutr 49, 2010, 127–132.
9. Xu B, Wang Y, Li J, Lin Q, Effect of prebiotic
xylooligosaccharides on growth performances and diges-
tive enzyme activities of allogynogenetic crucian carp
(Carassius auratus gibelio). Fish Physiol Biochem 35, 2009,
351–357.
10. Saier MH, and Mansour NM, “Probiotics and Prebiotics in
Human Health,” Journal of Molecular Microbiology
and Biotechnology, Vol. 10, No. 1, 2005, pp. 22-25.
doi:10.1159/000090345.
11. Arabbi PR, “Alimentos Funcionais: Aspectos Gerais,”
Nutrire, Vol. 21, No. 6, 2001, pp. 87-102.
12. Gibson GR, and Roberfroid MB, “Dietary Modulation of the
Human Colonic Microbiota-introducing the Concept of
Prebiotics,” The Journal of Nutrition, Vol. 125, No. 6, 1995,
pp. 1401- 1412.
13. Mussatto S I, and Mancilha IM, “Non-digestible Oligosac-
charides: A Review,” Carbohydrate Polimers, Vol. 68, No. 3,
2007, pp. 587-597. doi:10.1016/j.carbpol.2006.12.011.
14. Bosscher D, Loo-Van J and Franck A, “Inulin and
Oligofructose as Prebiotics in the Prevention of Intestinal
Infections and Diseases,” Nutrition Research Reviews, Vol.
19, No. 2, 2006, pp. 216-226. doi:10.1017/S0954422407249686.
15. Ouwehand AC, Derrien M, de Vos W, Tiihonen K and
Rautonen N, “Prebiotics and Other Microbial Substrates for
Gut Functionality,” Current Opinion in Biotechnology, Vol.
16, No. 2, 2005, pp. 212-217. doi:10.1016/j.copbio.2005.01.007
16. Macfarlane S, Macfarlane GT and Cummings JH, “Review
Article: Prebiotics in the Gastrointestinal Tract,” Alimen-
tary Pharmacology and Therapies, Vol. 24, No. 5, 2006, pp.
701-714. doi:10.1111/j.1365-2036.2006.03042.x
17. Kaur N and Gupta AK, “Applications of Inulin and
Oligofructose in Health and Nutrition,” Journal of Bio-
science, Vol. 27, No. 7, 2002, pp. 703-714. doi:10.1007/
BF02708379
18. Losada MA, and Olleros T, “Towards a Healthier Diet for
the Colon: The Influence of Fructooligosaccharides and
Lactobacilli on Intestinal Health,” Nutrition Research, Vol.
22, No. 1, 2002, pp. 71-84. doi:10.1016/S0271-5317(01)00395-
5
19. Wang X and Gibson GR, “Effects of the In Vitro Fermenta-
tion of Oligofructose and Inulin by Bacteria Growing in the
Human Large Intestine,” Journal of Applied Bacteriology,
Vol. 75, No. 4, 1993, pp. 373-380.
20. Silva LP and Nornberg JL, “Prebioticos na Nutricao de nao
Ruminantes,” Ciencia Rural, Vol. 33, No. 5, 2003, pp. 983-
990.
21. Manning TS and Gibson GR, “Prebiotics,” Best Practice
and Research Clinical Gastroenterology, Vol. 18, No. 2,
2004, pp. 287-298. doi:10.1016/j.bpg.2003.10.008
22. Gouveia F, “Food Industry: The Path of Innovation and
New Products,” Vol. 2, No. 5, 2006, pp. 32-37.
23. Pereira DIA and Gibson GR, “Effects of Consumption of
Probiotics and Prebiotics on Serum Lipid Levels in Humans,”
Critical Reviews in Biochemistry and Molecular Biology,
Vol. 37, No. 4, 2002, pp. 259-281. doi:10.1080/
10409230290771519
24. Coundray C, Demigne C and Rayssiguier Y, “Effects of Di-
etary Fiber on Magnesium Absorption in Animals and Hu-
mans,” The Journal of Nutrition, Vol. 133, No. 1, 2003, pp. 1-
4.
25. Roberfroid MB, “Dietary Fiber, Inulin, and Oligofructose: A
Review Comparing Their Physiological Effects,” Critical
Reviews in Food Science and Nutrition, Vol. 33, No. 2, 1993,
pp. 103-148. doi:10.1080/10408399309527616
26. Borges VC, “Oligassacarideos x Fibras Alimentares,”Revista
Brasileira de Nutricao Clinica, Vol. 12, No. 2, 1997, pp. 161-
164.
27. Flamm G, Glinsmann W, Kritchevsky D, Prosky L and
Roberfroid MB, “Inulin and Oligofructose as Dietary Fiber:
A Review of the Evidence,” Critical Reviews in Food Sci-

Journal of Pharmacy Research Vol.8 Issue 3.March 2014
V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330
321-330
ence and Nutrition, Vol. 41, No. 5, 2001, pp. 353-362.
doi:10.1080/20014091091841
28. Roberfroid MB, “Dietary Fiber, Inulin, and Oligofructose: A
Review Comparing Their Physiological Effects,” Critical
Reviews in Food Science and Nutrition, Vol. 33, No. 2, 1993,
pp. 103-148. doi:10.1080/10408399309527616
29. Passos LML and Park YK, “Fructooligosaccharides: Impli-
cations in Human Health Being and Use in Foods,” Ciencia
Rural, Vol. 33, No. 2, 2003, pp. 385-390.
30. Tuohy KM, Rouzaud GCM, Bruck WM and Gibson GR,
“Modulation of the Human Gut Microflora towards Improved
Health Using Prebiotics - Assessment of Efficacy,” Current
Pharmaceutical Design, Vol. 11, No. 1, 2005, pp. 75-90.
doi:10.2174/1381612053382331
31. Gibson GR, Willis CL and Van Loo J, “Non-digestible Oli-
gosaccharides and Bifidobacteria Implications for Health,”
International Sugar Journal, Vol. 96, No. 1150, 1994, pp.
381-387.
32. Hauly MCO, and Moscatto JA, “Inulin and Oligofructosis:
A Review about Functional Properties, Prebiotic Effects and
Importance for Food Industry,” Semina: Ciencias Exatas e
Tecnologicas, Vol. 23, No. 1, 2002, pp 105-118.
33. Spiegel JE, Rose R, Karabell P, Frankos VH and Schmitt DF,
“Safety and Benefits of Fructooligosaccharides as Food
Ingredients,” Food Technology, Vol. 48, No.1, 1994, pp.85-
89.
34. Costa GP and Waitzberg DL, “Efeitos Beneficos dos
Frutooligossacarideos na Saude Humana,” Revista
Brasileira de Medicina, Vol. 1, No. 7, 1997, pp. 6-7.
35. Lima PM, “FOS em Nutricao Enteral,” Revista Qualidadeem
Alimentacao - Nutricao, Vol. 4, No. 15, 2003, pp.26-27.
36. Tokunaga T, Oku T and Hosya N, “Utilization and Excretion
of a New Sweetener Fructooligosaccharide (Neosugar) in
Rats,” The Journal of Nutrition, Vol. 119, No. 4, 1989, pp.
553-559.
37. De Leenheer L, Production and use of inulin: Industrial real-
ity with a promising future. In Carbohydrates as organic
raw materials , vol. III, ed. H. Van Bekkun, H. Röper, and H.
Vorgen. Weinheim: Wiley-VCH,1996.
38. Crittenden,RG and Playne MJ, Production, properties and
applications of food-grade oligosaccharides. Trends in Food
Science and Technology, 7,1996, 353–361.
39. Roberfroid, MB and Delzenne N, Dietary fructans. Annual
Review Nutrition ,18,1998, 117–143.
40. Park YK and Almeida MM, Production of
fructooligosaccharides from sucrose by tranfructosylase
from Aspergillus niger . World Journal of Microbiology
and Biotechnology, 7, 1991, 331–334.
41. Roberfroid MB, Prebiotics: The concept revisited. Journal
of Nutrition, 137,2007, 830S–837S.
42. Cherbut C, Inulin and oligofructose in the dietary fi bre con-
cept. British Journal of Nutrition 87, Suppl. 2, 2002, S159–
S162.
43. Roberfroid MB and Delzenne NM, Dietary fructans. An-
nual Review of Nutrition, 18, 1998,117–143.
44. Coppa GV, Bruni S and Zampini L, Prebiotics in infant formu-
las: Biochemical characterization by thin layer chromatogra-
phy and high performance anion exchange chromatogra-
phy. Digestive and Liver Disease, 34, 2002, S124–S128.
45. Harmsen HJM, Elfferich P, Schut F, A 16S rRNA-targeted
probe for detection of lactobacilli and enterocci in faecal
samples by fl uorescent in situ hybridization.
MicrobialEcology in Health and Disease, 11, 1999, 3–12.
46. Guigoz Y, Rochat F and Prerruisseau-Carrier G, Effects of
oligosaccharide on the faecal flora and non-specifi c im-
mune system in elderly people. Nutrition Research,
22,2002,13–25.
47. Cummings JH, MacFarlane GT and Englyst H, “Prebiotic
Digestion and Fermentation,” American Journal of Clini-
cal Nutrition, Vol. 73, No. 2, 2001, pp. 415-420.
48. Modler HW, “Bifidogenic Factors – Sources, Metabolism
and Applications,” International Dairy Journal, Vol. 4, No.
5, 1994, pp. 383-407. doi:10.1016/0958-6946(94)90055-8
49. Hidaka H, Eida T, Takizawa T, Tokunaga T and Tashiro Y,
“Effects of Fructooligosaccharides on Intestinal Flora and
Human Health,” Bifidobacteria and Microflora, Vol. 5, No.
1, 1986, pp. 37-50.
50. Roberfroid MB, Van Loo JAE and Gibson GR, “The
Bifidogenic Nature of Chicory Inulin and Its Hydrolysis Prod-
ucts,” The Journal of Nutrition, Vol. 128, No. 1, 1998, pp. 11-
19.
51. Bouhnik Y, “Effects of Fructooligosaccharides Ingestion on
Fecal Bifidobacteria and Selected Metabolic Indexes of Co-
lon Carcinogenesis in Healthy Humans,” Nutrition and
Cancer, Vol. 26, No. 1, 1996, pp. 21-29. doi:10.1080/
01635589609514459
52. Moro G, Arslanoglu S, Stahl B, Jelinek J, Wahn U, Boehm G,
A mixture of prebiotic Oligosaccharides reduces the inci-
dence of atopic dermatitis during the fi rst six months of
Age, Arch Dis Child, 91,2006,814-819.
53. Waligora-Dupriet AJ, Campeotto F, Nicolis I, Effect of
oligofructose supplementation on gut microfl ora and well-
being in young children attending a day care centre, Int J
Food Microbiol, 113, 2007,108-113.
54. Duggan C, Penny ME, Hibberd P, Oligofructose-supple-
mented infant cereal: 2 randomized, blinded, community-
based trials in Peruvian infants, Am J Clin Nutr,77, 2003,
937-942.
55. Arslanoglu S, Moro GE, Schmitt J, Early dietary intervention
with a mixture of prebiotic oligosaccharides reduces the in-
cidence of allergic manifestations and infections during the
first two years of life, J Nutr, 138,2008,1091-1095.
56. Bouhnik Y, Raskine L, Champion K, Prolonged administra-
tion of low-dose inulin stimulates the growth of
bifidobacteria in humans, Nutr Res, 27, 2007,187-193.
57. Babu US, Sommers K, Harrison LM, Balan KV, Effects of
fructooligosaccharide-inulin on Salmonella-killing and in-
flammatory gene expression in chicken macrophages, Vet
immunopathology, Sep 15; 149(1-2),2012, 92-6. doi: 10.1016/
j.vetimm.2012.05.003. Epub 2012 May 8.

Journal of Pharmacy Research Vol.8 Issue 3.March 2014
V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330
321-330
58. Yancui Zhao, Kangsen Mai, Wei Xu, Wenbing
Zhang, Qinghui Ai, Yanjiao Zhang, XiaojieWang,Zhiguo
Liufu, Influence of dietary probiotic BacillusTC22 and
Prebiotic fructooligosaccharide on growth, immune re-
sponses and disease resistance against Vibrio
splendidus infection in sea cucumberApostichopus
japonicas, Journal of Ocean University of China , Volume
10, Issue 3, 2011,pp 293-300.
59. Vos AP, Knol J, Stahl B, M’Rabet L, Garssen J, Specific pre-
biotic oligosaccharides modulate the early phase of a mu-
rine vaccination response. Int Immunopharmacol,10, 2010,
619–625.
60. Delgado GTC, Tamashiro WMDSC, Junior MRM, Moreno
YMF, Pastore GM, The putative effects of prebiotics as
immunomodulatory agents. Food Res Int.,2011. doi:10.1016/
j.foodres.2011.07.032
61. Stam J, van Stuijvenberg M, Garssen J, Knipping K, Sauer
PJJ, A mixture of three prebiotics does not affect vaccine
specific antibody responses in healthy term infants in the
first year of life. Vaccine,2011. doi:10.1016/
j.vaccine.2011.07.110
62. Ohta A, Dietary fructooligosaccharides increase calcium
absorption and levels of mucosal calbinin-D9k in the large
intestine of gastrectomized rats, Scand J Gastroenterol,
33,1998,p. 1062-1068.
63. Ohta A, Baba S, Ohtsuki M, Takizawa T, Adachi T & Hara H,
In vivo absorption of calcium carbonate and magnesium
oxide from the large intestine in rats, J. Nutr.
Sci.Vitaminol,43,1997,35–46.
64. [64]Ohta A, Ohtsuki M, Baba S, Adachi T, Sakata T &
Sakaguchi E, Calcium and magnesium absorption from the
colon and rectum are increased in rats fed
fructooligosaccharides, J. Nutr, 125,1995, 2417–2424.
65. Morohashi T, Sano T, Ohta A & Yamada S, True calcium
absorption in the intestine is enhanced by
fructooligosaccharide feeding in rats,1998.
66. Jansson M, Induction of high phosphatase activity by alu-
minum in acid lakes, Arch Hydrobiol ,93,1981,32:44.
67. Heroux O, Peter D and Heggtveit, “Long-term Effect of Sub-
optimal Dietary Magnesium on Magnesium and Calcium
Contents of Organs, on Cold Tolerance, and on Life-span,
and its Pathological Consequences in Rats): “, J. Nut.,
107,1977,1640.
68. Tahiri M, Tressol JC, Arnaud J, Five-week intake of short-
chain fructo-oligosaccharides increases intestinal absorp-
tion and status of magnesium in postmenopausal women. J
Bone Miner Res, 16,2001,2152-2160.
69. Tahiri M, Tressol JC, Arnaud J, et al. Effect of short-chain
fructooligosaccharides on intestinal calcium absorption and
calcium status in postmenopausal women: a stable-isotope
study. Am J Clin Nutr, 77, 2003,449-457.
70. Ducros V, Arnaud J, Tahiri M, Influence of short-chain fructo-
oligosaccharides (sc-FOS) on absorption of Cu, Zn, and Se
in healthy postmenopausal women, J Am Coll Nutr,
24,2005,30-37.
71. Davidson MH, Synecki C, Maki KC, Drennen KB, Effects of
dietary inulin in serum lipids in men and women with
hypercholesterolaemia, Nutr Res ,3,1998,503-517.
72. Giacco R, Clemente G, Luongo D, et al. Effects of short-chain
fructo-oligosaccharides on glucose and lipid metabolism in
mild hypercholesterolaemic individuals, Clin Nutr,23.
2004,331-340.
73. Jackson KG, Taylor GRJ, Clohessy AM, Williams CM, The
effect of the daily intake of inulin on fasting lipid, insulin
and glucose concentrations in middle-aged men and
women, Br J Nutr , 82,1999,23-30.
74. Pedersen A, Sandstrom B, van Amelsvoort JMM, The effect
of ingestion of inulin on blood lipids and gastrointestinal
symptoms in healthy females, Br J Nutr, 78,1997,215-222.
75. Schaafsma G, Meuling WJ, van Dokkum W, Bouley C, Ef-
fects of a milk product, fermented byLactobacillus
acidophilus and with fructo-oligosaccharides added, on
blood lipids in male volunteers, Eur J Clin Nutr, 52,1998,436-
440.
76. Van Dokkum W, Wezendonk B, Srikumar TS, van den Heuvel
EG, Effect of nondigestible oligosaccharides on large-bowel
functions, blood lipid concentrations and glucose absorp-
tion in young healthy male subjects, Eur J Clin Nutr,
53,1999,1-7.
77. Williams CM, Jackson KG, Inulin and oligofructose: effects
on lipid metabolism from human studies, Br J Nutr ,87(suppl
2), 2002, S261-264.
78. Forcheron F, Beylot M, Long-term administration of inulin-
type fructans has no significant lipid-lowering effect in
normolipidemic humans, Metabolism, 56,2007,1093-1098.
79. Cummings JH, Christie S, Cole TJ, A study of fructo oli-
gosaccharides in the prevention of travellers’
diarrhea, Aliment Pharmacol Ther . 2001;15:1139-1145.
80. Waligora-Dupriet AJ, Campeotto F, Nicolis I, Effect of
oligofructose supplementation on gut microflora and well-
being in young children attending a day care centre, Int J
Food Microbiol ,2006, Sep 20. [Epub ahead of print]
81. Luo J, Van Yperselle M, Rizkalla SW, Chronic consumption
of short-chain fructooligosaccharides does not affect basal
hepatic glucose production or insulin resistance in type 2
diabetics, J Nutr , 130, 2000,1572-1577.
82. Alles MS, de Roos NM, Bakx JC, van de Lisdonk E, Zock PL,
Hautvast GA, Consumption of fructooligosaccharides does
not favorably affect blood glucose and serum lipid concen-
trations in patients with type 2 diabetes, Am J Clin Nutr,
69,1999,64-69.
83. Paineau D, Payen F, Panserieu S,The effects of regular con-
sumption of short-chain fructo-oligosaccharides on diges-
tive comfort of subjects with minor functional bowel
disorders,Br J Nutr, 2007 Aug 13. [Epub ahead of print]
84. Bittner AC, Croffut RM, Stranahan MC, Prescript-Assist
probiotic-prebiotic treatment for irritable bowel syndrome: a
methodologically oriented, 2-week, randomized, placebo-
controlled, double-blind clinical study, Clin Ther, 27, 2005,
755-761.

Journal of Pharmacy Research Vol.8 Issue 3.March 2014
V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330
321-330
Source of support: Nil, Conflict of interest: None Declared
85. Arslanoglu S, Moro GE, Schmitt J, Early dietary intervention
with a mixture of prebiotic oligosaccharides reduces the in-
cidence of allergic manifestations and infections during the
first two years of life, J Nutr, 138, 2008,1091-1095.
86. Olesen M, Gudmand-Hoyer E, Efficacy, safety, and tolerabil-
ity of fructooligosaccharides in the treatment of irritable
bowel syndrome, Am J Clin Nutr, 72, 2000,1570-1
87. De Paula JA, Carmuega E, Weill R. Effect of the ingestion of
a symbiotic yogurt on the bowel habits of women with func-
tional constipation. Acta Gastroenterol Latinoam, 38,
2008,16-25.
88. Fabrice Pierre, Pascale Perrin, Euphemie Bassonga, Francis
Bornet, Khaled Meflah and Jean Menanteau, Tcell status
influence colon tumor occurrence in Min mice fed short chain
fructo-oligosaccharides as a diet supplemet, Carcinogen-
esis , Vol 20 no, 1999, pp.1953-1956.
89. Pierre F, Perrin P, Champ M, Bomet F, Meflah K and
Menanteau J, Short –chain fructo-oligosaccharides reduce
the occurrence of colon tumors and develop gut-associated
lymphoid tissue in Min mice, Cancer Res, 57, 1997, 225-228.
90. Dove WF, Clipson L, Gould KA, Luongo C, Marshall DJ,
Moster AM, Newton MA and Jacoby RF, Intestinal neopla-
sia in the ApcMin mouse: independence from microbial and
natural killer (beige locus) status, Cancer Res,57,1997, 812-
814.
91. Dudley ME, Sundberg JP and Roopenian DC, Frequency
and histological appearance of adenomas in multiple intesti-
nal neoplasia mice are unaffected by severe combined im-
munodeficiency (scid) mutation, Int. J.Cancer, 65,1996, 249-
253.
92. Hori T, Matsumoto K, Sakaitani Y, Sato M, Morotomi M,
Effect of dietary deoxycholic acid and cholesterol on fecal
steroid concentration and its impact on the colonic crypt
cell proliferation in azoxymethane-treated rats. Cancer Lett,
124,1998,79-84.
93. Narisawa T, Magadia NE, Weisburger JH, Wynder EL, Pro-
moting effect of bile acids on colon carcinogenesis after
intrarectal instillation of N-methyl-N’-nitro-N-
nitrosoguanidine in rats, J Natl Cancer Inst ,53,1974,1093-
1097.
94. Nair PP, Role of bile acids and neutral sterols in carcinogen-
esis, Am J Clin Nutr, 48,1988, 768-774.
95. Breuer NF, Goebell H, Bile acids and cancer of the large
bowel,Dig Dis, 5,1987,65-77.
96. Yoram Bouhnik, Lotfi Achour, Damien Paineau, Michel
Riottot, Alain Attar and Francis Bornet, Four-week short
chain fructo-oligosaccharides ingestion leads to increasing
fecal bifidobacteria and cholesterol excretion in healthy eld-
erly volunteers, Nutrition Journal, 2007, 6:42
97. Teuri U, Vapaatalo H, Korpela R, Fructooligosaccharides
and lactulose cause more symptoms in lactose maldigesters
and subjects with pseudohypolactasia than in control lac-
tose digesters,Am J Clin Nutr , 69, 1999, 973-979.