Impact of a Resistant Dextrin on Intestinal Ecology: How Altering the Digestive Ecosystem with NUTRIOSE(R), a Soluble Fibre with Prebiotic Properties, May Be Beneficial for Health

Abstract

The prebiotic potential of NUTRIOSE®--a sugar-free, digestion-resistant dextrin--was evaluated in two randomized, placebo-controlled trials that included 48 and 40 healthy volunteers, respectively.
In study 1, the effect on colonic bacteria of NUTRIOSE® 10, 15 or 20 g/day administered for 14 days was examined; in study 2, gut microbial changes in response to NUTRIOSE® 8 g/day for 14 days were monitored using real-time polymerase chain reaction analysis.
NUTRIOSE® increased proliferation of Bacteroides and inhibited Clostridum perfringens in both studies, increased β-glucosidase activity (at 10 and 15 g/day) and decreased colonic pH (at 20 g/day). The increase in short-chain fatty acid production with NUTRIOSE® consumption was not statistically significant. There were no indications of gastrointestinal intolerance at any dose.
According to commonly accepted definitions, NUTRIOSE® is a prebiotic soluble fibre that provides a beneficial effect on colonic ecology while preserving digestive comfort.

Full text

The Journal of International Medical Research
2012; 40: 211 – 224 [first published online ahead of print as 40(1) 8]
211
Impact of a Resistant Dextrin on
Intestinal Ecology: How Altering the
Digestive Ecosystem with NUTRIOSE®, a
Soluble Fibre with Prebiotic Properties,
May Be Beneficial for Health
C LEFRANC-MILLOT1, L GUÉRIN-DEREMAUX1, D WILS1, C NEUT2, LE MILLER3AND
MH SANIEZ-DEGRAVE1
1Nutrition Direction, Roquette, Lestrem, France; 2Clinical Bacteriology Laboratory, College of
Pharmacy, University of Lille, France; 3SPRIM USA, San Francisco, California, USA
OBJECTIVES: The prebiotic potential of
NUTRIOSE®– a sugar-free, digestion-
resistant dextrin – was evaluated in two
randomized, placebo-controlled trials
that included 48 and 40 healthy
volunteers, respectively. METHODS: In
study 1, the effect on colonic bacteria of
NUTRIOSE® 10, 15 or 20 g/day administered
for 14 days was examined; in study 2, gut
microbial changes in response to
NUTRIOSE® 8 g/day for 14 days were
monitored using real-time polymerase
chain reaction analysis. RESULTS:
NUTRIOSE®increased proliferation of
Bacteroides and inhibited Clostridum
perfringens in both studies, increased
b-glucosidase activity (at 10 and 15 g/day)
and decreased colonic pH (at 20 g/day).
The increase in short-chain fatty
acid production with NUTRIOSE®
consumption was not statistically
significant. There were no indications of
gastrointestinal intolerance at any dose.
CONCLUSIONS: According to commonly
accepted definitions, NUTRIOSE®is a
prebiotic soluble fibre that provides a
beneficial effect on colonic ecology while
preserving digestive comfort.
KEY WORDS: BACTEROIDES; FERMENTATION; GLUCOSIDASE; INTESTINAL MICROBIOTA; LOW-DIGESTIBLE
CARBOHYDRATE; OLIGOSACCHARIDES
Introduction
NUTRIOSE®(Roquette, Lestrem, France) is a
glucose polymer derived from wheat
(NUTRIOSE®FB range) or maize starch
(NUTRIOSE®FM range) via a highly controlled
dextrinization process of partial hydrolysis
and subsequent repolymerization.1In
addition to typical α-1,4 and α-1,6 glucosidic
linkages, repolymerization results in other
linkages not found in starch, including
linear and branched linkages β-1,6, α-1,2
and/or β-1,2, α-1,3 and/or β-1,3, and β-1,4.
NUTRIOSE®is, therefore, resistant to
hydrolysis by endogenous glucidolytic
enzymes and can be classified as a soluble
dietary fibre with a total fibre content of

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almost 85% (NUTRIOSE®06), according to
the Association of Analytical Communities
method.1,2 Chromatography is used to tailor
the molecular weight distribution and to
increase fibre content further. Additional
refining steps – including the removal of
simple sugars and spray drying – result in a
product with mono- and disaccharide
content of < 0.5% dry weight.
NUTRIOSE®is a sugar-free dextrin that is
not absorbed in the ileum and remains
available for bacterial fermentation in the
colon.3This bacterial fermentation has been
shown to decrease colonic pH, alter the
microflora and induce the production of
short-chain fatty acids.3Wheat dextrin has
been shown to have similar fermentability to
inulin and partially hydrolysed guar gum
(PHGG)4or psyllium5in in vitro batch-
fermentation systems. Both wheat dextrin
and inulin decreased pH, but inulin resulted
in the production of significantly more
hydrogen and total gas.4In addition, wheat
dextrin and inulin produced significantly
more total short-chain fatty acids than PHGG
after 24 h.4Wheat dextrin, psyllium and
inulin produced similar short-chain fatty acid
concentrations at 24 h, but differences in
fermentation rates and gas production may
affect gastrointestinal tolerance.5NUTRIOSE®
has been shown to have beneficial effects in
humans, including increased lactobacilli
numbers, decreased faecal pH (from 6.6 to
6.1) and increased faecal α- and β-
glucosidase activities after consumption of 45
g/day for 35 days.6These results demonstrate
the prebiotic potential of NUTRIOSE®.
Prebiotics were originally defined as
nondigestible food ingredients that
beneficially affect the host by selectively
stimulating the growth and/or activity of one
(or a limited number) of the bacterial species
already resident in the colon and, thus,
attempt to improve host health.7 This
definition has been revised over time to
include an increase in beneficial bacteria
and/or a decrease in harmful bacteria, a
reduction in intestinal pH, the production of
short-chain fatty acids and changes in
bacterial enzyme concentrations.8Several in
vitro and in vivo studies (in rats and in
humans) have been undertaken to explore
the potential prebiotic effects of
NUTRIOSE®,6,9,10 and supplementation with
NUTRIOSE®was found to increase the
numbers of faecal lactobacilli.6
The aim of the present research was two-
fold: first, to determine the effect of three
different dosages of NUTRIOSE®on
Bacteroides and Clostridium perfringens
numbers; Bacteroides is the predominant
saccharolytic genus of a normal gut flora;11
secondly, to determine more precisely the gut
microbial changes that occur, using real-
time polymerase chain reaction (PCR)
analysis.
Subjects and methods
STUDY 1
Subjects and study design
This prospective, single-centre, randomized,
double-blind, placebo-controlled pilot study
evaluated the impact of three different doses
of NUTRIOSE®on the faecal flora of healthy
volunteers over a 15-day period. Healthy
male and female volunteers were locally
recruited by advertisement by the Clinical
Investigation Centre (CIC) at the Regional
Teaching Hospital, Lille, France, between
November 2002 and August 2003.
During a preinclusion visit, subjects
provided a medical history and underwent
physical examination. Inclusion criteria
were: age 18 – 45 years; regular intestinal
transit (meaning one or two stools per day, of
normal consistency, excreted without any
difficulty, for ≥ 3 months); no history of
medical or psychiatric disorders; no history

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of chronic gastrointestinal disorders;
affiliation to the French public welfare
system or similar. Exclusion criteria included:
infection or antibiotic therapy in the
previous 3 months; participation in any
other trial in the previous month; use of
drugs that may interfere with normal transit
(antidiarrhoeals, laxatives, intestinal anti -
septics, antibiotics); gluten or aspartame
intolerance; wheat flour allergy; constipation;
vegetarianism or veganism; consumption of
more than three glasses of beer or wine per
week; current pregnancy; subject under legal
guardianship; partial or complete legal
incapacity.
The Advisory Committee of People’s
Welfare in Biomedical Research in Lille,
Regional Teaching Hospital, Lille, France,
approved the study protocol (09/09/2002-CP
02/67), and subjects provided written
informed consent.
Diet and supplementation
Subjects were required to follow a low-residue
diet, containing a maximum of 20 g/day of
total dietary fibre, and abstain from
fermented dairy products containing bifidus,
yoghurt, ‘light’ food products (i.e. sugar-free
confectionery or beverages and artificial
sweeteners), dietary supplements (pre- and
probiotics) and meal substitutes. This diet
was followed for a 7-day preinclusion period,
or dietary lead-in period. On day 8, an
inclusion visit allowed investigators to
perform a clinical examination and record
potentially interfering events before
including and randomizing the subjects.
Fresh stools were sampled and analysed, and
the experimental products – either
NUTRIOSE®or placebo – were then
administered for ingestion, starting from day
8, for 14 days. On day 15 of the treatment
period (i.e. day 23 of the study), the final visit
took place.
Randomization of the subjects for
assignment into one of four groups was done
in blocks of 12 (blocks of two males and two
females) by the CIC, after drawing lots using
sealed envelopes pre-established by people
independent from the study. The placebo
group received 20 g/day glucose by mouth in
two equal doses for 14 days. The remaining
three groups received 10, 15 or 20 g/day
NUTRIOSE®(Roquette, Lestrem, France) by
mouth in two equal daily doses for 14 days.
Experimental products used in all groups
(including the placebo group) were rendered
identical in taste and sweetness by the
addition of aspartame. Both products were
provided in powder form and were dissolved
in 200 ml orange juice (given to all subjects
by the investigators) prior to consumption
with the afternoon and evening meals.
Faecal parameters
Subjects provided faecal samples at two time
points: day 8 (inclusion visit), and day 23
(final visit on the day following the 14-day
period of placebo/NUTRIOSE®consumption).
Fresh faeces was collected and transported at
ambient temperature in a sterile plastic
container containing a moistened
Anaerocult®A (Merck, Lyon, France), in
order to generate an anaerobic environment.
Bacteriological analysis was carried out
within 4 h of sample collection.
Samples were diluted and spread on
media specific for the culture of the different
types of bacteria studied, then incubated in
aerobic or anaerobic conditions as
appropriate. Bacterial cultures were counted
48 h after inoculation for aerobic bacteria
and 7 days after inoculation for anaerobic
bacteria. Total anaerobic species were
counted (Columbia agar medium
[bioMérieux, Craponne, France] with 0.03%
cysteine hydrochloride and 0.5% glucose,
and supplemented with 5% horse blood);

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separate counts were done for the anaerobic
species: Bacteroides (Bacteroides bile esculin
agar medium [Oxoid, Dardilly, France]);
Bifidobacterium spp (Columbia agar medium
with 0.03% cysteine hydrochloride and 0.5%
glucose, and adjusted to pH 5.0 by adding
propionic acid); Chlostridium innocuum
(Columbia–mannitol agar medium with
0.03% cysteine hydrochloride and 1%
mannitol [bioMérieux]); C. perfringens
(brain–heart infusion broth with added
0.05% cysteine hydrochloride, then lactose–
sulphite broth if positive); and Lactobacillus
spp (de Man–Rogosa–Sharpe agar medium
[Oxoid]). Separate counts were also
performed for aerobic (facultative anaerobic)
species; Staphylococcus spp (mannitol salt
agar medium [bioMérieux]) and Enterococcus
spp (MacConkey agar medium
[bioMérieux]).
In addition, pH, β-glucosidase enzyme
activity and short-chain fatty acid levels
were assessed at both time points. The pH
and enzyme activity were measured
according to the method of van den Heuvel
et al.9Short-chain fatty acid levels were
assessed using the method described in
Guérin-Deremaux et al.12
Statistical analyses
Statistical analyses were carried out with
SPSS®statistical software, version 9.0 (SPSS
Inc., Chicago, IL, USA) for Windows®. The
Kolmogorov–Smirnov and Shapiro–Wilk
tests were used to assess the normality of
distribution of clinical and biological
parameters. Homogeneity of the groups was
analysed before the subjects received
NUTRIOSE®/placebo treatment. Values were
expressed as mean ± SD. Intragroup
comparison of clinical parameters was
carried out using the Friedman test for paired
samples. Between-group tests were
performed using Student’s independent-
sample t-test or the Kruskal–Wallis test,
depending on the assumptions of normality.
A P-value < 0.05 was considered to be
statistically significant.
STUDY 2
Subjects and study design
This single-centre, randomized, double-
blind, placebo-controlled, parallel-group
study with aged-matched subjects evaluated
the effect of NUTRIOSE®supplementation on
faecal Bacteroides (total population and B.
fragilis specifically) and C. perfringens
numbers.
Female volunteers were recruited from the
Food Manufacturer in YiWu, Zhejiang
Province, China, between December 2007
and March 2008. Advertisements were
placed on site by the CIC of Xinhua Hospital,
affiliated to Shanghai Jiao Tong University
School of Medicine, Shanghai, China.
Inclusion criteria were: age 25 – 59 years;
ability to understand the study procedures
and provide informed consent; moderate
intestinal disorders (including one or more of
the following symptoms: diverticulosis or
nonspecific symptoms; stool types 1 or 2 on
the Bristol Stool Form Scale;13 clinical
constipation; difficult, painful, or extended
faecal exoneration); body mass index (BMI)
24 – 27.9 kg/m2. Exclusion criteria included:
participation in any other trial in the
previous 2 months; known chronic
constipation; currently treated gastro -
intestinal symptoms; analgesic treatment
(except aspirin or paracetamol); regular
intake of laxatives or other remedies to
promote digestion in the 2 weeks prior to the
study (at least once per week); consumption
of dairy products or supplements containing
probiotics in the 10 days prior to the study;
current diarrhoea, or frequent urgent evacua -
tion; current dietary fibre supplementation
(except from food sources); previous

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Prebiotic effects of NUTRIOSE®, a resistant dextrin
contraindication to fibre supplements
(Crohn’s disease); wheat allergy; dietary
constraints limiting the consumption of pre-
and probiotics; antibiotic therapy in the
previous 3 months; diseases that contra -
indicate dietary fibre supplementation.
The ethical committee ‘Institutional
Review Board of Shanghai’, China
(07/12/2007-EC [2007] No. 003) approved
the study and all subjects provided written
informed consent.
An urn randomization scheme stratified by
age (29 – 39, 40 – 49 and 50 – 59 years) and
BMI (using two distinct ranges: 24.0 – 25.9
kg/m2and 26.0 – 27.9 kg/m2) was employed to
assign participants to the groups. A fully
detailed protocol to preserve blinding was
communicated to the CIC on the logistics of
assigning participants to one of the two groups
according to this specified urn design. Subjects
received either glucose 8 g/day (in dextrose
liquid form) or NUTRIOSE®8 g/day, diluted in
248 ml of apple juice, once a day for 14 days.
Supplements were provided to subjects,
already diluted in a total of 14 separate bottles
of apple juice, for daily consumption before
breakfast (at 08.00 h). Participants were asked
to maintain their regular diet while avoiding
the following in order to limit nonspecific
fermentations and nonspecific digestive
microflora selection: dairy products with
added cultures, asparagus, salsify, rye bread,
artichokes, leeks, garlic, onions and bananas.
Faecal parameters
Subjects provided faecal samples at baseline
(between day –3 and day 0) and between day
11 and day 14. Real-time PCR analyses were
performed using group-specific primers for C.
perfringens and Bacteroides (developed by
Matsuki et al.).14 DNA was extracted from 20
mg faecal samples and real-time PCR
amplification of 16S rDNA was performed in
order to identify and quantify Bacteroides
fragilis and C. perfringens populations. Real-
time PCR was performed with an external
control using a commercial kit (SYBR®Green
I; Takara Bio Inc., Tokyo, Japan) according to
the manufacturer’s instructions. Each
reaction mixture (25 µl) was composed of
10 × buffer (Mg2+plus), 2.5 µl deoxyribo -
nucleotide triphosphate 200 µM, 1:75 000
dilution of SYBR®Green I, 11 ng/µl of
TaqStart™ antibody (Clontech Laboratories
Inc., Palo Alto, CA, USA), 1 U of Taq DNA
polymerase (Takara Bio Inc.), and each of
the specific primers at a concentration of
0.25 µM. Primers were obtained14 from the
appropriate gene database (GenBank®;
http://www.ncbi.nlm.nih.gov/genbank/).
About 100 ng DNA from each sample was
used for real-time PCR using an ABI 7300HT
thermal cycler (Applied Biosystems, Foster
City, CA, USA). The thermal cycling
programme consisted of one cycle of 94 °C
for 5 min, then 40 cycles of denaturation at
94 °C for 20 s, annealing at 55 or 50°C for
20 s, and elongation at 72 °C for 50 s,
followed by a final cycle of 94°C for 15 s. The
bacterial PCR products were quantified using
real-time PCR, by measuring the gene-
specific amplification curves and melting
curves.
Bacteroides (total and B. fragilis) and C.
perfringens populations were assessed at the
clinical centre laboratory of Xinhua Hospital
affiliated with Shanghai Jiao Tong University
School of Medicine, Shanghai, China. Spot
faecal samples were collected in a sterile gas-
tight bag, in a plastic container containing an
Anaerocult®A strip to create anaerobic
conditions. Subjects recorded the time of
defaecation. Samples were freeze-dried, stored
at –18 °C, bulked as an individual’s 24-h
sample, weighed, ground into powder and
homogenized, and portions of approximately
10 g each were stored at ambient temperature
(protected from oxygen, humidity and light)

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in airtight plastic bottles until the time of
analysis. Agar plates were inoculated using
general anaerobic medium broth
supplemented with 1% glucose, and cultured
anaerobically at 37°C for 12 – 48 h. The
resulting colonies were evaluated by
microscopic examination and 2-(4-amidino -
phenyl)-6-indolecarbamidine dihydrochloride
staining,15or by assessment of resistance to
the antibiotics erythromycin, rifampicin,
kanamycin and vancomycin.
Information regarding undesirable
gastrointestinal events was collected daily
during the 15 days of the study. Volunteers
completed a notebook indicating whether
they had experienced any of the following:
abdominal pain, bloating, flatulence or
other symptoms. The intensity of the event
was graded by the subject himself as being
minor (grade 1), moderate (grade 2) or
strong (grade 3); absence of any symptom
was also recorded (grade 0).
Statistical analyses
The number of subjects was calculated to
provide a minimum of 85 – 90% statistical
power in detecting a significant dose
relationship, allowing for a maximum
overall drop-out rate of 5% in each group
and taking into account the short duration
of the study.
Data were expressed as mean ± SD. One
endpoint of the study was improvement in
digestive discomfort and the assessment of
frequency and severity of constipation, based
on the Bristol Stool Form Scale.13 Multiple
regression analysis and generalized linear
modelling were used to characterize the
dose–response relationship.16 Paired Student’s
t-tests were utilized to assess pre- to post-
treatment changes in faecal parameters. The
analyses were carried out using SAS and S-
plus (SAS/STAT software version 9.2, SAS
Institute Inc., Cary, NC, USA). A P-value
< 0.05 was considered to be statistically
significant.
Results
STUDY 1
Study 1 originally recruited 49 healthy
volunteers (24 females and 25 males); all
were randomized, but one subject dropped
out after randomization due to an
undesirable event (precise information is not
available), leaving 48 subjects in total. Six
female subjects were included in each group,
while seven male subjects were included in
the NUTRIOSE® 10 g group, six in the
placebo and NUTRIOSE®15 g groups, and
five in the NUTRIOSE®20 g group. The study
population were healthy subjects of
European origin, with a mean age of 28
years, mean weights (62.2 kg for females and
75.5 kg for males) within normal ranges,
and a mean BMI of 24 ± 3 kg/m2for males
and 22 ± 3 kg/m2for females. There were no
statistically significant differences between
the groups in terms of baseline demographic
parameters.
After 14 days, consumption of 10 g/day
NUTRIOSE®resulted in a significant increase
in saccharolytic flora numbers (Bacteroides)
compared with baseline (P< 0.05; Fig. 1).
There were no intragroup significant
differences in the numbers of other
potentially beneficial bacteria
(Bifidobacterium spp, Lactobacillus spp)
whatever the dosage ingested. No other
statistical differences were observed between
any of the different treatment groups and
placebo in terms of potentially beneficial
bacteria.
Consumption of 15 g/day NUTRIOSE®led
to a significant decrease in C. perfringens
numbers after 14 days compared with
baseline (P< 0.05; Fig. 2). There were no
intragroup significant changes in the
numbers of other potentially harmful bacteria

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Prebiotic effects of NUTRIOSE®, a resistant dextrin
FIGURE 1: Bacteroides numbers (mean ± SD) in faecal cultures from healthy subjects
before and after oral administration of NUTRIOSE®10 g/day for 14 days. Results are
expressed in log colony forming units (CFU)/g. *P< 0.05 compared with baseline,
Kruskal–Wallis test
Before
9.0
9.5
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
0
No. of bacteria (log CFU/g)
After
*
FIGURE 2: Clostridium perfringens numbers (mean ± SD) in faecal cultures from
healthy subjects before and after oral administration of NUTRIOSE®15 g/day for 14
days. Results are expressed in log colony forming units (CFU)/g. *P< 0.05 compared
with baseline, Kruskal–Wallis test
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
0
No. of bacteria (log CFU/g)
Before After
*

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Prebiotic effects of NUTRIOSE®, a resistant dextrin
(C. innocuum, Staphylococcus spp, Enterococcus
spp) whatever the dosage ingested. In terms of
these bacteria, no statistically significant
differences were observed in the different
groups compared with placebo.
There was a significant intragroup
decrease in faecal pH with the consumption
of 20 g/day NUTRIOSE®(from 6.67 ± 0.4 to
5.99 ± 0.5 after 14 days; P< 0.05; Fig. 3).
Faecal pH decreases showed statistically
significant between-group differences (P<
0.05) at the end of the study, with a more
pronounced decrease being observed in the
20 g/day group compared with variations
observed in the other groups.
There were no statistically significant
differences in short-chain fatty acid levels
before and after supplementation with
NUTRIOSE®at any dose. Levels of acetate,
propionate and butyrate were higher after
NUTRIOSE®supplementation, but these
increases were not statistically significant.
Oral supplementation with NUTRIOSE®
significantly increased intragroup faecal
β-glucosidase activity in the 10 g/day and
15 g/day groups compared with the
placebo group (24.4 ± 14.0 and 22.6 ± 13.0
versus 12.9 ± 8.2 U/g, respectively; P< 0.05;
Fig. 4).
Study subjects reported very good digestive
tolerance for NUTRIOSE®: 10 and 20 g/day
dosages resulted in significantly more
frequent (P< 0.05) but milder flatulence than
in the placebo group. The incidence of
abdominal pain was significantly higher (P<
0.05) in the placebo group compared with the
other groups, but with minor intensity, and
the incidence of bloating was similar in all
groups, remaining unchanged by
NUTRIOSE®consumption. There were no
cases of treatment-related drop-out, with a
mean observance of 99%.
FIGURE 3: Faecal pH (mean ± SD) in healthy subjects before and after oral
administration of NUTRIOSE®20 g/day for 14 days. *P< 0.05 compared with
baseline, Shapiro–Wilk test
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
0
Faecal pH
Before After
*

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Prebiotic effects of NUTRIOSE®, a resistant dextrin
STUDY 2
Study 2 recruited 40 females, who were
stratified by age and BMI before being
randomly assigned to one of the two
treatment groups. There were no statistical
differences in the demographic data between
subjects in the placebo and NUTRIOSE®
groups: the mean ages of the groups were 48.7
and 43.9 years, and the mean BMI values
were 24.6 and 24.6 kg/m2, respectively.
Consumption of NUTRIOSE®8 g/day for 14
days resulted in a significant intragroup
increase in faecal Bacteroides numbers (P <
0.05; Fig. 5) and a significant intragroup
decrease in faecal C. perfringens numbers (P <
0.05; Fig. 6) compared with baseline, as
determined by real-time PCR. There was also a
significant increase in the Bacteroides count
FIGURE 4: Faecal β-glucosidase activity (mean ± SD) in healthy subjects after oral
administration of NUTRIOSE®10, 15 or 20 g/day or glucose 20 g/day (control) for 14
days. *P< 0.05 compared with baseline, Shapiro–Wilk test
Control
(glucose 20 g/day)
10 15
NUTRIOSE® (g/day)
20
10
15
20
25
30
35
40
45
50
55
60
65
70
75
0
Faecal β-glucosidase activity (U/g)
*
*

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Prebiotic effects of NUTRIOSE®, a resistant dextrin
(P< 0.00001) and a significant decrease in the
C. perfringens count (P< 0.0016) within the
NUTRIOSE®group, between the beginning
and the end of the study, compared with the
variation observed in the placebo group. There
were no statistically significant between-group
differences in faecal classification according to
the Bristol Stool Form Scale categories.13
Discussion
The present studies demonstrated that
NUTRIOSE®has a specific colonic fermen -
tation pattern in humans and induces
beneficial effects on the colonic environment,
in accordance with the findings of other
research.6The specific colonic fermentation
pattern is likely to be related to the molecular
FIGURE 5: Faecal Bacteroides numbers (mean ± SD) assessed by real-time polymerase
chain reaction in healthy subjects before and after oral administration of NUTRIOSE®
8 g/day for 14 days. Results are expressed in log colony forming units (CFU)/g. *P<
0.05 compared with baseline, paired Student’s t-test
Before
8.4
8.6
8.8
9.0
9.2
9.4
0
No. of bacteria (log CFU/g)
After
*
FIGURE 6: Faecal Clostridium perfringens numbers (mean ± SD) assessed by real-time
polymerase chain reaction in healthy subjects before and after oral administration of
NUTRIOSE®8 g/day for 14 days. Results are expressed in log colony forming units
(CFU)/g. *P< 0.05 compared with baseline, paired Student’s t-test
Before
3.1
3.2
3.3
3.4
3.5
3.6
3.7
0
No. of bacteria (log CFU/g)
After
*

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structure of the dietary fibre and its
physicochemical characteristics. NUTRIOSE®,
a glucose polymer, may stimulate the
proliferation of colonic bacteria that are able
to adapt to nondigestible carbohydrates,17
including the genus Bacteroides. Bacteroides are
commonly found in the human intestine
where they assist in the breakdown of food
and produce valuable nutrients and energy:
these bacteria are known to contribute to a
healthy colonic ecology.18 The present studies
found that consumption of 8 or 10 g/day of
NUTRIOSE®for 14 days increased the numbers
of Bacteroides. In addition, numbers of C.
perfringens, a potentially harmful bacterium,
were decreased by the consumption of
NUTRIOSE®8 or 15 g/day for 14 days.
The growth of beneficial bacteria induces
an increase in digestive enzymes including β-
glucosidase, an inducible enzyme produced in
particular by Bacteroides.19 The increase in β-
glucosidase activity after consumption of
NUTRIOSE®10 or 15 g/day for 14 days in the
present study 1 indicates significant changes
in the metabolic activity of the colonic flora;17
this indicates a possible adaptation of the
bacterial microflora to dietary substrates,
leading to an optimization of energy
harvesting.20 This is consistent with another
study of NUTRIOSE®consumption, which
found an increase in both α- and β-
glucosidase and in the amount of branched
glucose (assumed to be a measure of
enzymatic activity) present in faeces.4The
action of β-glucosidase on residual undigested
polysaccharides, for example vegetable
residues, results in increased bioavailability of
minerals and other micronutrients.21
Increased fermentation leads to a
reduction in colonic (and therefore faecal)
pH. A weak decrease in gut pH, coupled with
propionic acid production, is known to be
associated with a decrease in potentially
harmful Gram-negative bacteria such as C.
perfringens,22 as observed during the present
studies. This acidic environment may also
help to solubilize minerals and further
increase their absorption.23
Colonic short-chain fatty acids – indicators
of the fermentation processes occurring after
fibre consumption – are difficult to monitor
in human clinical studies.24 Study 1 described
here examined faecal short-chain fatty acids
but found no significant changes after
consumption of NUTRIOSE®. This conflicts
with findings from animal research, where
short-chain fatty acid levels were increased
after NUTRIOSE®consumption.12
The present research reinforced the
classification of NUTRIOSE®as a prebiotic, in
line with the definition: ‘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’.25 A prebiotic has been further defined
as, ‘a nonviable food component that confers
a health benefit on the host associated with
modulation of the microbiota’.26 According to
accepted definitions, a prebiotic fibre must
alter the balance of gut microflora in a
positive manner; it must induce an increase
in beneficial bacteria and a decrease in
deleterious bacteria. In vitro, animal and
human studies have demonstrated that the
resistant dextrin in NUTRIOSE®is fermented,
lowers faecal pH and generates short-chain
fatty acids.4,6,27 The present studies found that
dietary supplementation with dextrin not
only increased Bacteroides numbers, but also
decreased the numbers of pathogenic bacteria
such as C. perfringens, in accordance with
other studies.6
Well-known prebiotics include oligo -
saccharides such as inulin, fructo-oligo -
saccharides and galacto-oligo saccharides; all
have a long history of good safety profiles.28
The use of prebiotics in infant nutrition

222
C Lefranc-Millot, L Guérin-Deremaux, D Wils et al.
Prebiotic effects of NUTRIOSE®, a resistant dextrin
reduces the risk of gastroenteritis and
infection, improves general well-being and
reduces the incidence of allergic symptoms
such as atopic eczema.28 Products that cause
a selective modification in the composition
of the gut microbiota could induce beneficial
physiological effects in the colon and
contribute towards reducing the risk of
dysbiosis,28but there is some concern about
excess production of digestive gas when they
are consumed in large amounts.29
As a soluble dietary fibre, NUTRIOSE®is
mostly resistant to digestion in the small
intestine, being largely fermented in the
colon, and shows an outstanding digestive
tolerance.6,30 This allows consumption in the
amount best suited to achieving the desired
beneficial changes to the gut ecosystem, as
demonstrated in both short- and long-term
use. The digestive tolerance threshold for
NUTRIOSE®has been set at 45 g/day for
healthy adults in short-term use:30 short-
term use is defined using studies in which
digestive complaints of the tested volunteers
are measured to determine a digestive
threshold following 1 week’s maximum
consumption of the tested compound. The
laxative threshold dose of NUTRIOSE®has
been set at 100 g/per day.6Several factors
contribute to these findings. First,
NUTRIOSE®is only partially digested in the
upper part of the intestinal tract, and the
high degree of polymerization induces a
lower osmotic pressure and a slower
fermentation rate.30 Secondly, the dextrin is
slowly fermented throughout the colon,
allowing the short-chain fatty acids
produced to be progressively absorbed,
inducing little osmotic effect3(compared
with dietary fibres such as fructans that are
rapidly fermented in the proximal colon).31
Finally, the type of food matrix in which
NUTRIOSE®is included, and the daily fibre
consumption of the subject, may also
influence digestive tolerance.3
Prebiotics may improve colon health via
the reduction of inflammation and the
stimulation of intestinal immunity.28 Animal
studies have found that the consumption of
NUTRIOSE®significantly increases the levels
of intestinal mediators involved in the
regulation of pain, inflammation and
immunity,32,33 suggesting a potential
influence of NUTRIOSE® on the regulation of
local immunity.
NUTRIOSE®has a positive impact on
diverse anthropometric and metabolic
parameters,27,34,35 possibly due to the
modulation of microbial ratios in the gut
flora.36,37 In addition, the slow and
prolonged production of short-chain fatty
acids along the length of the colon may
provide long-lasting energy and delay or
reduce feelings of hunger.38 Studies have
described the dose-dependent increase in
peptide-tyrosine tyrosine and proglucagon
mRNA expression by butyrate in vivo, which
may play an important role in the control of
energy homeostasis39,40 and promote
satiety.41 Further research is required to
elucidate the underlying mechanism.
The present research had several
limitations. First, the data were derived from
two separate studies. Secondly, faecal
sampling is not necessarily representative of
total excretion. Thirdly, the method used for
counting bacteria in study 1 may have led to
viable cells being undercounted, since plate
counting assumes that every colony is
founded by a single cell, and requires
lengthy incubation for colonies to become
visible. Despite these limitations, this
research supported and confirmed the
efficacy of NUTRIOSE®as a prebiotic fibre
ingredient or supplement, at doses fully
compatible with both a beneficial biological
effect on colonic ecology and a preserved
digestive comfort. Additional studies, using

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Copyright © 2012 Field House Publishing LLP
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Acknowledgements
This study was supported by a grant from
Roquette Lestrem, France, the manufacturers
of NUTRIOSE®. We wish to thank Valérie
Macioce, Alex Han and Neelesh Varde
(Roquette) as well as Kelly Zhang (SPRIM) for
their assistance. We gratefully acknowledge:
SPRIM China, Ltd, for the design, execution
and analysis of study 2; Charlie Zhang as the
trial monitor; researchers and clinicians from
the Clinical Bacteriology Laboratory of the
College of Pharmacy, University of Lille,
France and the Clinical Investigation Centre,
CHU Lille, France; researchers and clinicians
from Xinhua Hospital, affiliated with
Shanghai Jiao Tong University School of
Medicine, Shanghai, China.
Conflicts of interest
C Lefranc-Millot, L Guérin-Deremaux, D
Wils and MH Saniez-Degrave are employed
by Roquette, the manufacturers of
NUTRIOSE®. C Neut and LE Miller had no
conflicts of interest to declare in relation to
this article.
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Author’s address for correspondence
Dr Catherine Lefranc-Millot
Nutrition Direction, Roquette, 62080 Lestrem, France.
E-mail: catherine.lefranc@roquette.com
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C Lefranc-Millot, L Guérin-Deremaux, D Wils et al.
Prebiotic effects of NUTRIOSE®, a resistant dextrin