Embed Size (px)
Citation preview
SCIENTIFICPUBLICATIONS
FACTSHEETS
............................................................................................................................................................................................................................
.............................................................................................................................................................................................................................
..........................................................................................................................................................................................................................................................................................................................
............................................................................................................................................................................................................................
..........................................................................................................................................................................................................................................................................................................................
............................................................................................................................................................................................................................
.............................................................................................................................................................................................................................
..........................................................................................................................................................................................................................................................................................................................
.............................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
............................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
............................................................................................................................................................................................................................
.............................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
.............................................................................................................................................................................................................................
PDF ACTIVIA.indd 1 15/11/12 13:51
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
NOTE
The strain Bifi dobacterium animalis sp. lactis DN-173 010 is deposited in the Collection Nationale de Cultures de Micro-Organismes (CNCM), at the Institute Pasteur (Paris, France) as Bifi dobacterium animalis sp. lactis CNCM I-2494.
The nomenclature DN-173 010 can be found in several scientifi c publications.
PDF ACTIVIA.indd 2 15/11/12 13:51
INTR
OD
UC
TIO
N
Gastrointestinal comfort refers to the ability of the digestive system to function properly and support a good quality of life. This is thus an important aspect of human health.
It is multifactorial, and includes physical and psychological components that are integrated as global perception. It is affected by digestive complaints such as abdominal pain, fl atulence, bloating, borborygmi and altered bowel habit (constipation, diarrhea), leading to discomfort (cf. fi gure below).
INTRODUCTION
Digestive complaints are widely experienced by a large part of the general population, ranging from healthy subjects to subjects with Irritable Bowel Syndrome (IBS).
There is a continuous increase of the severity and frequency of these digestive complaints from healthy subjects to subjects with IBS. IBS subjects have more severe gastrointestinal symptoms1, and a higher sensitivity to physiological digestive events.2
BORBORYGMI
DIARRHEALOOSE STOOLS
ABDOMINALPAIN
FLATULENCE
BLOATING
CONSTIPATION/HARD STOOLS
GIDISCOMFORT
PDF ACTIVIA.indd 3 15/11/12 13:51
INTR
OD
UC
TIO
N
REFERENCES: 1. Leibbrand, R., Cuntz, U. and Hiller, W. - Assessment of functional gastrointestinal disorders using the Gastro-Questionnaire. Int. J. Behav. Med. 2002. 2. Spiller, R., Aziz, Q., Creed, F., Emmanuel, A., Houghton, L.A., Hungin, P., Jones, R., Kumar, D., Rubin, G., Trudgill, N. and Whorwell, P.J. - Guidelines on the irritable bowel syndrome: mechanisms and practical management - Gut 2007. 3. Longstreth, G.F., Thompson, W.G., Chey, W.D., Houghton, L.A., Mearin, F. and Spiller, R.C. 2006. - Functional bowel disorders – Gastroenterology 2006. 4. Drossman, D.A., Whitehead, W.E. and Camilleri, M. - Irritable bowel syndrome: a technical review for practice guideline development. – Gastroenterology 1997. 5. Drossman, D.A., Camilleri, M., Mayer, E.A. and Whitehead, W.E. - AGA technical review on irritable bowel syndrome. Gastroenterology 2002. 6. De Giorgio, R., Barbara, G., Stanghellini, V., Cremon, C., Salvioli, B., De Ponti, F. and Corinaldesi, R. - Diagnosis and therapy of irritable bowel syndrome. Aliment. Pharmacol. Ther. 2004. 7. Tack, J., Fried, M., Houghton, L.A., Spicak, J. and Fisher, G. - Systematic review: the effi cacy of treatments for irritable bowel syndrome - a European perspective - Aliment. Pharmacol. Ther. 2006. 8. Katsinelos, P., Lazaraki, G., Kountouras, J., Paroutoglou, G., Oikonomidou, I., Mimidis, K., Koutras, C., Gelas, G., Tziomalos, K., Zavos, C., Pilpilidis, I. and Chatzimavroudis, G. - Prevalence, bowel habit subtypes and medical care-seeking behaviour of patients with irritable bowel syndrome in Northern Greece. - Eur. J. Gastroenterol. Hepatol. 2009. 9. Corazziari, E., Bytzer, P., Delvaux, M., Holtmann, G., Malagelada, J.R., Morris, J., Muller-Lissner, S., Spiller, R.C., Tack, J. and Whorwell, P.J. - Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome - Aliment. Pharmacol. Ther. 2003. 10. Irvine, E.J., Witehead, W.E., Chey, W.D., Matsueda, K., Shaw, M., Talley, N.J. and Veldhuyzen van Zanten, S.J.O. - Design of treatment trials for functional gastrointestinal disorders - Gastroenterology 2006.
IBS is characterised by the presence of abdominal pain or discomfort, associated with altered bowel function.3 This is not a life-threatening condition but it is the most common chronic gastrointestinal disorders, affecting up to 20% of the general population in Europe and North America.4-8
Scientifi c experts recognized IBS as a sensitive and appropriate model to demonstrate the effi cacy of a dietary intervention intended to improve the gastrointestinal comfort on general population, in addition to effi cacy trials conducted on adults having minor GI discomfort.
Since gastrointestinal comfort is dependent upon the perception of sensations arising from the gut (e.g. bloating, fl atulence) and upon bowel function, it is measured with overall assessments that integrate all these parameters.3,9,10 These assessments should be performed with validated tools, questionnaires, which allow subjects to self-report their discomfort level.10 Several other parameters can also be measured such as individual digestive complaints (abdominal pain/discomfort, bloating, fl atulence, borborygmi) or physical parameters (abdominal distension).
Four clinical studies consistently demonstrate that Activia® consumption improves gastrointestinal comfort (cf. part Activia® Effi cacy studies). 2 studies are on healthy population and 2 are on IBS-C (IBS-constipation predominant), and evaluate as primary criteria either digestive comfort with questionnaires or abdominal distension with physical measurements.
In addition, studies evaluate some mode of action of the product, such as the effects on transit time and bowel movements. Other studies demonstrate the ability of the strain Bifi dobacterium lactis CNCM I-2494 to survive throughout the GI tract. This part has been enriched recently with fi rst insights on gut microbiota modulation.
Today, a total of 9 clinical trials on the mechanisms of action of Activia® accompany the science on the digestive comfort benefi t (cf. part Activia® Mechanism of action studies).
PDF ACTIVIA.indd 4 15/11/12 13:51
............................................................................................................................................................................................................................
...........................................................................................................................................................................................................................
..
..........................................................................................................................................................................................................................................................................................................................
............................................................................................................................................................................................................................
..........................................................................................................................................................................................................................................................................................................................
............................................................................................................................................................................................................................
...........................................................................................................................................................................................................................
..........................................................................................................................................................................................................................................................................................................................
...........................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
............................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
............................................................................................................................................................................................................................
...........................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
...........................................................................................................................................................................................................................
1. ACTIVIA® EFFICACY STUDIES
STUDIES ON HEALTHY POPULATIONGuyonnet et al., 2009 a Guyonnet et al., 2009 b
STUDIES ON IBS-C POPULATIONAgrawal et al., 2009 Guyonnet et al., 2007
PDF ACTIVIA.indd 5 15/11/12 13:51
PDF ACTIVIA.indd 6 15/11/12 13:51
AC
TIVI
A® E
FFIC
AC
Y S
TUD
IES
: HE
ALT
HY
PO
PU
LATI
ON
GUYONNET et al., 2009 aGuyonnet D, Woodcock A, Stefani B, Trevisan C, Hall C. Fermented milk containing Bifi dobacterium lactis DN-173 010 improved self-reported digestive comfort amongst a general population of adults. A randomized, open-label, controlled, pilot study. Journal of Digestive Diseases, 2009; 10: 61-70.
STUDY METHODOLOGYThe study was a randomized, controlled, open-label, parallel group trial. 360 healthy volunteers (18–65 yo), with self-reported digestive discomfort and a normal stool frequency, consumed daily either 1x125g serving (n=144) or 2x125g servings (n=147) of Activia®, over 14 days. The control group (n=69) followed their usual diet without intervention.
EVALUATION CRITERIA Self-reported change in digestive comfort (one
question after 14 days of product consumption: “Think back over the last 2 weeks, how has your digestive comfort changed?”, using a 5-point Likert scale; evaluation after 14 days of product consumption).
Bother from different digestive symptoms (Self-completed, 20-item questionnaire; evaluation at baseline, and at the end of product consumption).
RESULTS Self-reported changes in general digestive comfort:
The percentage of subjects reporting an improvement of digestive comfort was signifi cantly higher in both Activia® groups (1-pot group 82.5%; 2-pot group 84.3%) vs. the control group (2.9%).
The between-group differences confi rmed each of the two Activia® groups differed signifi cantly from the control group (p<0.001).
There was no signifi cant difference between 1-pot and 2-pot groups.
Digestive symptoms:
For both Activia® groups, there was a signifi cantly greater improvement (p<0.001) vs. control for almost all symptom scores, including bloated feeling, excessive or trapped wind, swollen stomach and feeling heavy, lethargic or uncomfortable due to digestive troubles.
PDF ACTIVIA.indd 7 15/11/12 13:51
CONCLUSIONDaily consumption of 1 or 2x125g of Activia® servings during 14 days may exert positive effects on self-reported digestive comfort in a general population of healthy adults in real-life conditions.
Beyond this global improvement, the bother from most of the digestive symptoms assessed may be reduced in a high and signifi cant percentage of participants.
Scores are expressed as percentage of participants per category (worse, no change or better digestive comfort).
Perc
enta
tge
of p
artic
ipan
ts (%
)
WORSE NO CHANGE BETTER
CHANGE IN PERCEIVED DIGESTIVE COMFORT AFTER ACTIVIA® OR CONTROL CONSUMPTION
100
90
80
70
60
50
40
30
20
10
0
* *
Activia® 1=pot Activia® 2=pot Control
*p<0.001 vs. control
GUYONNET et al., 2009 a
PDF ACTIVIA.indd 8 15/11/12 13:51
AC
TIVI
A® E
FFIC
AC
Y S
TUD
IES
: HE
ALT
HY
PO
PU
LATI
ON
GUYONNET et al., 2009 bGuyonnet D, Schlumberger A, Mhamdi L, Jakob S, Chassany O. Fermented milk containing Bifi dobacterium lactis DN-173 010 improves gastrointestinal well-being and digestive symptoms in women reporting minor digestive symptoms: a randomized, double-blind, parallel, controlled study. British Journal of Nutrition, 2009; 102(11):1654-62.
STUDY METHODOLOGYThe study was a randomized, double-blind, controlled, parallel clinical trial on 197 women (18–60 yo) with minor digestive symptoms but without gastrointestinal disorders.The subjects consumed daily 2x125g servings of either Activia® (n=100), or 2x125g servings of a non fermented dairy product with low content of lactose (lactose content similar to the test product) (n=97), over 4 weeks. There was an additional follow up 4 weeks after the cessation of product consumption (washout period).
EVALUATION CRITERIAOverall self-reported assessment of gastrointestinal well-being (weekly, from week 1 to the end of the study):
3-point Likert scale: worse, no change, better.
15-point Likert scale to precise the level of worsening or improvement.
Digestive symptoms (weekly, from week 1 to the end of the study):
Composite score and frequency of individual digestive symptoms: abdominal pain/discomfort, bloating, fl atulence/passage of gas, borborygmi and rumbling stomach.
5-point Likert scale.
Bowel function (daily):
Stool frequency (expressed as number of bowel movement/week).
Stool consistency (Bristol Stool Scale).
Health Related Quality of Life (at baseline, at 4 weeks (end of product consumption) and at 8 weeks (end of washout period)):
Self-administration of 2 questionnaires: FBA (Food Benefi t Assessment) and PGWBI (Psychological General Well-Being Index).
Completion at baseline, at 4 weeks (end of product consumption) and at 8 weeks (end of washout period).
RESULTS DOUBLE-BLIND PERIOD:
Gastrointestinal well-being
The percentage of women reporting an improvement in their GI well-being was signifi cantly (p=0.006) higher in the Activia® group vs. control group (OR=1.69, [95% CI 1.17- 2.45]), as well as the percentage of responders for GI well-being (p=0.025; 52.0% vs. 36.1% respectively, OR=1.92 [95% CI 1.09-3.40]).
Frequency of digestive symptoms
Over the 4 weeks of product consumption, results showed a signifi cant decrease in the composite score of digestive symptoms (p=0.044; LS mean=-0.57 [95% CI -1.12; -0.02]) and in borborygmi frequency (p=0.016; LS mean=-0.22 [95% CI -0.40;-0.04]) in the Activia® group compared to the control group.
The decrease in fl atulence frequency was signifi cantly higher in the Activia® group vs. control group at weeks 1, 2 and 4 (p<0.05).
No signifi cant differences were observed in bloating, abdominal pain or discomfort scores.
Bowel function
A signifi cant (p=0.02) improvement of the stool consistency was observed in the Activia® group vs. the control group. Stool frequency did not differ between groups.
PDF ACTIVIA.indd 9 15/11/12 13:51
Health Related Quality of Life
FBA digestive comfort dimension score (primary HRQoL endpoint), signifi cantly increased (p=0.027) after 4 weeks of product consumption in the Activia® group vs. control group (FBA questionnaire). No difference was observed between groups for other HRQoL dimensions. PGWBI scores did not differ between groups over time.
WASHOUT PERIOD:
The percentage of women reporting an improvement in their GI well-being did not differ signifi cantly between groups at the end of the washout period.
The percentage of responders strongly decreased without signifi cant differences between the Activia® and the control groups (8.0% vs.11.3%; OR 0.68 [95%CI 0.26; 1.77]).
The composite score of digestive symptoms signifi cantly decreased (p<0.05) over the 4-weeks in the control group when compared with the Activia® group. No signifi cant difference in the changes of frequency for each individual symptom was observed between the groups.
No differences were observed between groups for stool frequency, consistency or HRQoL dimensions.
A responder was defi ned as a subject having an improvement of their gastrointestinal well-being at least 2 weeks among the 4 weeks; results are expressed as percentage.
Rat
e of
resp
onde
rs fo
r GI
wel
l-bei
ng (%
)
4 weeksdouble-blind period
4 weekswashout period
OVERAL ASSESSMENT OF GI WELL-BEING (RATE OF RESPONDERS)
60
50
40
30
20
10
0
* Activia®
Control
CONCLUSIONThe daily consumption of 2x125g servings of Activia® during 4 weeks signifi cantly improved GI well-being and digestive symptoms in the general population of women reporting minor digestive symptoms. The effect of Activia® was no longer observed once consumption was stopped.
*p=0.025
GUYONNET et al., 2009 b
PDF ACTIVIA.indd 10 15/11/12 13:51
AC
TIVI
A® E
FFIC
AC
Y S
TUD
IES
: IB
S-C
PO
PU
LATI
ON
STUDY METHODOLOGYIn this randomized, controlled, double-blind, parallel group study, 38 women (18-70 yo) with Irritable Bowel Syndrome with predominant constipation (IBS-C) consumed daily 2x125g servings of either Activia® (n=18) or a non fermented dairy product with low content of lactose (lactose content similar to the test product) (n=20), over 4 weeks.
EVALUATION CRITERIA Abdominal distension (Plethysmography; 24h
evaluation at baseline and after 4 weeks of product consumption).
Colonic and small bowel transit time (Radiopaque marker and hydrogen breath test methods; evaluation at baseline and after 4 weeks of product consumption).
Data represents the median. Percentage change in maximal distension=(maximal distension post treatment - maximal distension at baseline)/maximal distension at baseline x 100.
*p<0.05
Cha
nge
in m
axim
al d
iste
nsio
n (%
)
PERCENTAGE CHANGE IN MAXIMAL DISTENSION AFTER ACTIVIA®
OR CONTROL CONSUMPTION
0
-15
-30
-45
-60
-75
-90 *Activia®Control
Overall IBS symptoms severity and digestive symptoms severity (i.e. abdominal pain ⁄ discomfort, bloating, fl atulence; daily evaluation reported in a diary).
Stool frequency (expressed as number of bowel movement/week; daily evaluation).
Stool consistency (Bristol Stool Scale; daily evaluation).
AGRAWAL et al., 2009Agrawal A, Houghton L.A, Morris J, Reilly B, Guyonnet D, Goupil-Feuillerat N, Schlumberger A, Jakob S, Whorwell P.J. Clinical trial: the effects of a fermented milk product containing Bifi dobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Alimentary Pharmacology and Therapeutics, 2009; 29(1): 104-114.
PDF ACTIVIA.indd 11 15/11/12 13:51
RESULTS Abdominal distensionAfter 4 weeks of product consumption, a trend towards a reduction in mean abdominal distension during the day (AUC values, -1.52 cm 95% CI [3.33, 0.39], p=0.096) and a signifi cant reduction in the percentage change in maximal distension (Activia®: -77.1% vs. control: -28.6%, p<0.05) were observed in the Activia® group, in comparison with the control group.
Colonic and small bowel transit timeColonic and small bowel transit times were signifi cantly reduced in the Activia® group, in comparison with the control group (respectively -12.2h, 95%CI [-22.8,-1.6], p=0.026 and -1.2h, 95%CI [-2.3, 0.0], p=0.049).
CONCLUSIONDaily consumption of 2x125g servings of Activia® over 4 weeks, signifi cantly reduced abdominal distension in association with acceleration of gastrointestinal transit in IBS-C women. Activia® improved digestive comfort by reducing overall IBS symptom severity and digestive symptoms.
MEAN ABDOMINAL DISTENSION BEFORE AND AFTER ACTIVIA® OR CONTROL CONSUMPTION
Mea
n di
sten
sion
(cm
)
Hours
6
5
4
3
2
1
0
Control group Control group
Before product consumption
Activia® group Activia® group
1321 3 4 5 6 7 8 9 10 11 12
Mea
n di
sten
sion
(cm
)
Hours
6
5
4
3
2
1
0
After product consumption
1321 3 4 5 6 7 8 9 10 11 12
Overall IBS and digestive symptoms Over the 4 weeks of Activia® consumption, overall symptom severity signifi cantly improved (p=0.032), abdominal pain⁄discomfort signifi cantly decreased (p=0.044), and bloating (p=0.059) and fl atulence (p=0.092) tended to reduce, compared with control group.
Stool consistency and frequencyA trend to a normalization of stool consistency (p=0.058) was also observed without modifi cation of stool frequency.
AGRAWAL et al., 2009
PDF ACTIVIA.indd 12 15/11/12 13:51
AC
TIVI
A® E
FFIC
AC
Y S
TUD
IES
: IB
S-C
PO
PU
LATI
ON
STUDY METHODOLOGYIn this randomized, controlled, double-blind, parallel study, 267 subjects (18-65 yo) with Irritable Bowel Syndrome with predominant constipation (IBS-C) consumed daily 2x125g servings of either Activia® (n=135) or a heat-treated yoghurt containing non-living bacteria (n=132), over 6 weeks.
EVALUATION CRITERIA Digestive discomfort dimension of the Functional
Digestive Disorder Quality of Life questionnaire: FDDQL (Evaluation at baseline and after 3 and 6 weeks of product consumption).
Rate of responders for the digestive discomfort dimension of FDDQL questionnaire (defi ned as subjects having an improvement ≥10% of digestive discomfort score vs. baseline; evaluation after 3 and 6 weeks of product consumption).
Global digestive symptoms (7 points Likert scale; evaluation after 3 and 6 weeks of product consumption).
Bloating and abdominal pain (6-points Likert scale; evaluation at baseline and at weeks 3 and 6 of product consumption).
Stool frequency (expressed as number of bowel movement/week; daily evaluation).
Stool consistency (Bristol Stool Scale; daily evaluation).
RESULTS Global digestive symptomsThe FDDQL digestive discomfort score improved (p<0.001) in both groups at week 3 (Activia®: 10.7 ± 14.5; control: 7.5 ± 16.5) and week 6 (Activia®: 12.2 ± 16.2; control: 13.5 ± 19.3). The evolution of global digestive symptoms scores did not differ between groups at weeks 3 and 6.
RespondersThe responder rate for the discomfort dimension of the FDDQL questionnaire was signifi cantly higher at week 3 in the Activia® group (65.2%) vs. the control group (47.7%) (p=0.003).
Bloating and abdominal painBloating score signifi cantly (p<0.001) improved in both groups as compared to baseline, this improvement being signifi cantly (p=0.03) higher in Activia® group vs. control at week 3. Abdominal pain signifi cantly (p<0.001) improved in both groups as compared to baseline without difference between groups.
Stool frequency and consistencyIn a subgroup of subjects with less than 3 stools ⁄ week (n=19), stool frequency signifi cantly increased over 6 weeks in the Activia® group vs. the control group (p<0.001).
GUYONNET et al., 2007 Guyonnet D, Chassany O, Ducrotte P, Picard C, Mouret M, Mercier C.H, Matuchansky C. Effect of a fermented milk containing Bifi dobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial. Alimentary Pharmacology and Therapeutics, 2007; 26 (3): 475-486.
PDF ACTIVIA.indd 13 15/11/12 13:51
CONCLUSIONDaily consumption of 2x125g servings of Activia® during 6 weeks improved digestive comfort. This study suggests a benefi cial effect of Activia® on the FDDQL digestive discomfort score and bloating in subjects with IBS-C. A positive effect on stool frequency in subjects having less than 3 stools per week was also observed.
*p=0.03
Sco
reS
core
:1=
no b
loat
ing
6=ve
ry im
porta
nt
Baseline Week 3
BLOATING BEFORE AND AFTER 3 AND 6 WEEKS OF ACTIVIA® OR CONTROL CONSUMPTION
4
3,5
3
2,5
Activia®
Control
RATE OF RESPONDERS FOR DIGESTIVE COMFORT DIMENSION AFTER 3 AND 6 WEEKS OF ACTIVIA® OR CONTROL CONSUMPTION
*p=0.003
Res
pond
er ra
te (%
)
Week 3 Week 6
60
50
40
30
20
10
0
17.5%* 6.2%
Activia®
Control
Week 6
*
GUYONNET et al., 2007
PDF ACTIVIA.indd 14 15/11/12 13:51
............................................................................................................................................................................................................................
...........................................................................................................................................................................................................................
..
..........................................................................................................................................................................................................................................................................................................................
............................................................................................................................................................................................................................
..........................................................................................................................................................................................................................................................................................................................
............................................................................................................................................................................................................................
...........................................................................................................................................................................................................................
..........................................................................................................................................................................................................................................................................................................................
...........................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
............................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
............................................................................................................................................................................................................................
...........................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
...........................................................................................................................................................................................................................
2. ACTIVIA® MECHANISM OF ACTION STUDIES
TRANSIT TIME & BOWEL MOVEMENTYang et al., 2008 Nishida et al., 2008 Marteau et al., 2002
STRAIN SURVIVAL &GUT MICROBIOTA MODULATIONMcNulty et al., 2011Rochet et al., 2008 Collado et al., 2006 Duez et al., 2000Pochart et al., 1992 Berrada et al., 1991
PDF ACTIVIA.indd 15 15/11/12 13:51
PDF ACTIVIA.indd 16 15/11/12 13:51
AC
TIVI
A® M
EC
HA
NIS
M O
F A
CTI
ON
STU
DIE
S: T
RA
NS
IT T
IME
& B
OW
EL
MO
VE
ME
NT
STUDY METHODOLOGYIn this randomized, double-blind, placebo-controlled, parallel group study, 135 healthy Chinese women with constipation (less than 3 stools/week; increased stool hardness; non-organic constipation and habitual constipation) (25-65 yo), consumed daily 100g of either Activia® (n=67) or an acidifi ed milk containing non-living bacteria (n=68), over 2 weeks.
EVALUATION CRITERIA Stool frequency (expressed as number/week;
evaluation at baseline, and after 1 and 2 weeks of product consumption).
Stool consistency (Bristol stool scale; evaluation at baseline, and after 1 and 2 weeks of product consumption).
Defecation condition (4 grade score, evaluation at baseline, and after 1 and 2 weeks of product consumption).
RESULTS After 1 and 2 weeks of Activia® consumption, stool frequency signifi cantly increased (p<0.01) and defecation conditions (p<0.01) and stool consistency signifi cantly improved (week 1: p<0.01, week 2: p<0.05), in comparison to the control group.
CONCLUSIONDaily consumption of 100g of Activia® during 2 weeks improved stool frequency and consistency as well as defecation conditions, in Chinese women with constipation.
**: intra group comparison p<0.01##: inter group comparison p<0.01
Sto
ol fr
eque
ncy
(n/w
k)
Baseline Week 1 Week 2
STOOL FREQUENCY AFTER ONE OR TWO WEEKS OF ACTIVIA® OR CONTROL CONSUMPTION
7
6
5
4
3
2
1
0
**
## ##
**
Activia®
Control
YANG et al., 2008 Yang Y, He M, Hu G, Wei J, Pages P, Yang X, Bourdu-Naturel S. Effect of a fermented milk containing Bifi dobacterium lactis DN-173 010 on Chinese constipated women. World Journal of Gastroenterology, 2008; 14(40): 6237-6243.
PDF ACTIVIA.indd 17 15/11/12 13:51
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
PDF ACTIVIA.indd 18 15/11/12 13:51
AC
TIVI
A® M
EC
HA
NIS
M O
F A
CTI
ON
STU
DIE
S: T
RA
NS
IT T
IME
& B
OW
EL
MO
VE
ME
NT
EVALUATION CRITERIA Oro-fecal transit time (Colored marker method,
evaluation at baseline and after 2 weeks of product consumption). 35 subjects.
Stool frequency, quantity, color and shape; (stool frequency expressed as number per week; color and shape defi ned according to scale and model respectively, daily evaluation recorded in a diary). 43 subjects.
Fecal microfl ora analysis (enumeration by plate counting, evaluation at baseline, and after 2 weeks of product consumption). 14 subjects.
STUDY METHODOLOGYIn this randomized, double-blind, placebo-controlled, cross-over study, 50 healthy Japanese women (mean age 19.43 ± 1.62 yo) were divided in 2 groups. The fi rst group (n=25) started with 2x85g servings of Activia® daily, then consumed 2x85g servings of a control product without B. lactis DN-173 010 daily. The second group (n=25) began with the control product and then consumed Activia® (same quantities daily). Each ingestion period lasted 2 weeks with a 6 weeks interval period between ingestion of each products.
RESULTS In the overall population, intestinal transit time was signifi cantly reduced after Activia® consumption (p<0.05) as compared with baseline but not compared to the control group. In subjects with slow transit time (>40 hours, 17 subjects), consumption of Activia® tended to reduce the transit time (p=0.055) and increase stool frequency (p<0.05) compared to the control group. The Bifi dobacterium cell count and the Bifi dobacterium ratio of intestinal microfl ora signifi cantly increased during the Activia® consumption (p<0.05). With regard to the quantity, colour, shape and characteristics of faeces, no signifi cant differences were observed between the two groups.
NISHIDA et al., 2008Nishida S, Ishikawa Y, Iino H. Effect of Bifi dobacterium lactis DN-173 010 on the Intestinal Transit Time, the Condition of Defecation and Intestinal Microfl ora: A randomized, Double-blind, Placebo-controlled, Cross-over Study among Healthy Japanese Women. Pharmacometrics 2008; 74 (5/6):99-106.
Values represent the mean ± S.D. *Signifi cantly different compared with baseline (p<0.05) #p=0.055 compared with control
Totaln=35
-18:16 -8:48 -46:58
-9:55 -4:08 -24:48-8:21 -4:40 -22:10
Fast transit timen=18
Slow transit timen=17
Tran
sit t
ime
(h)
Baseline Control Activia® Baseline Control Activia® Baseline Control Activia®
ORO-FECAL TRANSIT TIME BEFORE AND AFTER ACTIVIA® OR CONTROL CONSUMPTION
100
75
50
25
0
*
*
*#
CONCLUSIONDaily consumption of 2x85g servings of Activia® during 2 weeks, improved the intestinal transit time and increased the stool frequency, especially in Japanese women with a slow transit time.
PDF ACTIVIA.indd 19 15/11/12 13:52
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
PDF ACTIVIA.indd 20 15/11/12 13:52
AC
TIVI
A® M
EC
HA
NIS
M O
F A
CTI
ON
STU
DIE
S: T
RA
NS
IT T
IME
& B
OW
EL
MO
VE
ME
NT
STUDY METHODOLOGYIn this randomized, controlled, double-blind, multicenter, cross-over study, 32 healthy women (18-45 yo) were divided in two groups. The fi rst group (n=17) started with 3x125g servings of Activia® daily, then consumed 3x125g servings of a yoghurt daily. The second group (n=15) began with the yoghurt and then consumed Activia® (same quantities daily). Each ingestion period lasted 10 days, with a 10 days interval period between ingestion of each product.
CONCLUSIONDaily consumption of 3x125g servings of Activia® signifi cantly reduced colonic transit time in women. This effect was more pronounced in women with initial slower transit time.
EVALUATION CRITERIA Colonic transit times: total right, left and
sigmoid (Radio-opaque marker method, evaluation at baseline and after each product ingestion period).
Fecal bile salts, pH, microbial mass and weight (Evaluation at the end of each ingestion period).
RESULTSIn the total population, both colonic and sigmoid transit times were significantly (p<0.05) shortened in the Activia® group, compared to the control group, but no difference was observed vs. baseline.
In the subgroup of subjects with an initial transit time >40 hours, both colonic and sigmoid transit times were significantly (p<0.05) shortened in the Activia® group vs. the control group and vs. baseline.
Fecal mass, pH, bacterial mass and bile acids were not significantly modified.
MARTEAU et al., 2002Marteau P, Cuillerier E, Méance S, Gerhardt MF, Myara A, Bouvier M, Bouley C, Tondu F, Bommelaer G, Grimaud JC. Bifi dobacterium animalis strain DN-173 010 shortens the colonic transit time in healthy women: a double-blind, randomized, controlled study. Alimentary Pharmacol & Therap, 2002;16:587-93.
Values: mean ± SD Two values having different letters within a single line are statistically signifi cantly different (p<0.05).
Whole population (n=32) Subjects with colonic transit time >40 h (n=21)
Transit Time (h) Baseline Activia® Control Baseline Activia® Control
Colonic 55.2 ± 28.0ab 51.5 ± 30.2a 60.7 ± 27.1b 70.4 ± 21.8a 62.4 ± 29.8b 71.9 ± 26.5a
Sigmoid 25.2 ± 18.9ab 21.6 ± 14.9a 26.8 ± 14.2b 32.8 ± 18.3a 27.1 ± 14.9b 32.1 ± 13.1a
COLONIC AND SIGMOID TRANSIT TIME IN WHOLE POPULATION AND WOMEN WITH COLONIC TRANSIT TIME >40H
PDF ACTIVIA.indd 21 15/11/12 13:52
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
PDF ACTIVIA.indd 22 15/11/12 13:52
AC
TIVI
A® M
EC
HA
NIS
M O
F A
CTI
ON
STU
DIE
S: S
TRA
IN S
UR
VIV
AL
& G
UT
MIC
RO
BIO
TA M
OD
ULA
TIO
N
STUDY METHODOLOGY2 approaches: a “humanized” animal model and a controlled human study.Animal model: 10 germ-free mice, colonized with 15 well characterized bacteria originated from human gut, received either 1x2 gavages within 24h or 3x2 gavages within 24h (over 3 weeks) of the 5 Activia® strains (2.107 CFU in total for each gavage).Human study: 7 healthy female adult monozygotic twin pairs consumed daily 2x4oz (=113g) servings of Activia® during 7 weeks.
EVALUATION CRITERIAAnimal model: Sequencing technologies on bacteria from faeces
(Metagenomics = which bacteria are there?; Metatranscriptomics = what are bacteria doing?; evaluation pre-treatment, during treatment, post-treatment).
Mesurement of metabolites in urine samples (Metabolomics = what molecules have been produced?; 3 measures before colonization, the day of the fi rst inoculation, post-treatment).
Human study: Quantifi cation of Bifi dobacterium animalis subsp.
lactis in faeces (qPCR, evaluation pre-treatment, during treatment, post-treatment).
Sequencing technologies on bacteria from faeces (Metagenomics, Metatranscriptomics, evaluation pre-treatment, during treatment, post-treatment).
Stool parameters and frequency (daily).
RESULTSAmong the 14 healthy humans, from the week 1 to the week 7 of Activia® consumption, the level of Bifi dobacterium animalis subsp. lactis CNCM I-2494 was high in feces. 4 weeks after the cessation of Activia® consumption, levels decreased to below the limits of detection in all participants.
No detection of signifi cant impact of Activia® consumption on global dominant microbiota composition in humans, and minor modifi cation in mice (no statistical signifi cance).
Gene expression of the gut microbes was modulated: Activia® (product and strains) could promote the
effi cacy of utilization of plant derived polysaccharides by the microbiota.
Activia® (product and strains) could promote the production of short chain fatty acids by the microbiota.
To end Bifi dobacterium animalis subsp. lactis CNCM I-2494 (DN-173 010) is active in the gut and appears to utilize xylo-oligosaccharides (XOS) that mainly originate from plant dietary components.CM I-2
McNULTY et al., 2011 McNulty N.P, Yatsunenko T, Hsiao A, Faith J.J, Muegge B.D, Goodman A.L, Henrissat B, Oozeer R, Cools-Portier S, Gobert G, Chervaux C, Knights D, Lozupone C.A, Knight R, Duncan A.E, Bain J.R, Muehlbauer M.J, Newgard C.B, Heath A.C, Gordon J.I. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Science Translation Medicine, 2011; 3(106):106ra106.
CONCLUSIONAfter the daily consumption of 2x4oz servings of Activia® during 7 days, Bifi dobacterium animalis subsp. lactis CNCM I-2494 was detected throughout the human gastrointestinal tract.
When healthy people consumed Activia®, the global composition of the gut microbiota (bacteria living in the colon) remained stable, but the gene expression of the gut microbes was modulated.
PDF ACTIVIA.indd 23 15/11/12 13:52
Abu
ndan
ce o
f B. a
nim
alis
sub
sp. l
actis
log 10
(cel
l equ
ival
ents
/g fe
ces)
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
Pre4 Pre2 Pre1 FMP1 FMP2 FMP4 FMP7 Post2 Post4
Detection Limit
MOUSE AND HUMAN GUT MICROBIAL COMMUNITIES SHARE TRANSCRIPTIONAL RESPONSES TO ACTIVIA® INVOLVING ECS (ENZYME
COMMISSION) RELATED TO CARBOHYDRATE METABOLISM
LEVELS OF BIFIDOBACTERIUM ANIMALIS SUBSP. LACTIS IN HUMAN FECAL SAMPLES COLLECTED PRIOR TO, DURING AND AFTER CONSUMPTION OF ACTIVIA®
(qPCR, LOG10 (CELL EQUIVALENTS/g FECES))
% N
orm
aliz
ed c
ount
s
MOUSE MOUSE MOUSEHUMAN HUMAN HUMAN
RelativeFold-Changein expression
-10
-2
1
2
10
d14
pre-
treat
men
td1
5 tre
atm
ent
d42
mul
ti-tre
atm
ent
d42
sing
le-tr
eatm
ent
d14
pre-
treat
men
td1
5 tre
atm
ent
d42
mul
ti-tre
atm
ent
d42
sing
le-tr
eatm
ent
d14
pre-
treat
men
td1
5 tre
atm
ent
d42
mul
ti-tre
atm
ent
d42
sing
le-tr
eatm
ent
Pre
1A
ct 1
Act
4
Post
4
Pre
1A
ct 1
Act
4
Post
4
Pre
Act
ivia
®
Act
ivia
® (1
w)
Act
ivia
® (4
w)
Post
Act
ivia
®
10-2.5
10-3
10-1.5
10-4
10-4.5
10-6
EC2.4.1.20Cellobiosephosphorylase
EC3.1.1.11Pectinesterase
EC3.2.1.65Levanase
McNULTY et al., 2011
PDF ACTIVIA.indd 24 15/11/12 13:52
AC
TIVI
A® M
EC
HA
NIS
M O
F A
CTI
ON
STU
DIE
S: S
TRA
IN S
UR
VIV
AL
& G
UT
MIC
RO
BIO
TA M
OD
ULA
TIO
N
STUDY METHODOLOGYIn this randomized, open, parallel study, 12 healthy subjects (24-46 yo) consumed daily either 3x125g servings (6.6.1010 CFU/day) of Activia® (n=6) or 1g (2.1.1011 CFU/day) of freeze-dried powder of B. lactis DN-173 010 (n=6), over 7 days. The follow up period lasted 10 days.
EVALUATION CRITERIAEvaluation at baseline, at the end of product consumption and at the end of the follow-up period of:
Survival of Bifi dobacterium animalis sp. lactis in faeces (Colony immunoblotting, Fluorescent In Situ Hybridization (FISH) and Polymerase Chain Reaction (PCR)-Temporal Temperature Gradient Gel Electrophoresis (PCR-TTGE).
Determination of fecal enzyme activities and metabolites.
RESULTS According to the quantifi cation by the immunoblotting method, the mean number of B. animalis sp. lactis DN-173 010 was ≥ 108 CFU/g of faeces, in 5 out of 6 subjects, in both groups, after 7 days of product consumption. With PCR-TTGE, B. lactis DN-173 010 patterns were detected for 11 out of 12 subjects. No major modifi cations were observed in either the dominant members of the fecal microbiota or their activities. of
QUANTIFICATION BY IMMUNODETECTION (colony immunoblotting) OF B. lactis DN-173 010 IN FAECES AFTER ACTIVIA® CONSUMPTION
Data are presented as CFU/g of faeces. UD: Under Detection limit (<104 CFU/g faeces)
ROCHET et al., 2008 Rochet V, Rigottier-Gois L, Ledaire A, Andrieux C, Sutren M, Rabot S, Mogenet A, Bresson J.L., Cools S, Picard C, Goupil-Feuillerat N, Doré J. Survival of Bifi dobacterium animalis DN-173 010 in the fecal microbiota after administration in lyophilised form or in fermented product - A randomized study in healthy adults. Journal of Molecular Microbiology and Biotechnology, 2008; 14: 128-136.
Lyophilised form Fermented product
Subject Day 0 Day 7 Day 17 Subject Day 0 Day 7 Day 17
1 LF UD >109 UD 2 FP UD 4.7x108 UD
4 LF UD 8.2x108 UD 3 FP UD 8.3x108 UD
5 LF UD 4.5 x108 UD 6 FP UD 1.9 x108 UD
8 LF UD UD UD 7 FP UD 2.1 x107 6.4x105
10 LF UD 2.3 x109 UD 9 FP UD UD UD
11 LF UD 1.0 x107 105 12 FP UD 1.0 x107 1.0x107
Mean 3.9 x108 Mean 1.1 x108
CONCLUSIONAfter the daily consumption of 3 x 125g servings of Activia® or 1g of freeze-dried powder during 10 days, B. lactis DN-173 010 survived passage through the gastrointestinal tract.
PDF ACTIVIA.indd 25 15/11/12 13:52
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
PDF ACTIVIA.indd 26 15/11/12 13:52
AC
TIVI
A® M
EC
HA
NIS
M O
F A
CTI
ON
STU
DIE
S: S
TRA
IN S
UR
VIV
AL
& G
UT
MIC
RO
BIO
TA M
OD
ULA
TIO
N
STUDY METHODOLOGYIn this non randomized, non controlled, open trial including 12 healthy volunteers (25-40 yo), 10 subjects consumed daily 250ml of Activia® (n=10) over 4 weeks, 1 subject ingested no product (negative control) and 1 subject ingested daily 250ml of Activia® for 3 months prior study (positive control). The follow up period lasted 4 weeks.
EVALUATION CRITERIA Detection of bifi dobacteria genus (Enumeration by
plate counting and Fluorescent In Situ Hybridization (FISH); evaluation at baseline, and each week of product consumption and follow up periods).
Identifi cation of B. animalis sp. lactis (Polymerase Chain Reaction (PCR)).
Identifi cation of B. animalis sp. lactis DN-173 010 profi le (Amplifi ed Ribosomal DNA Restriction - PCR (ADRA-PCR); evaluation at baseline, and each week of product consumption and follow up periods).
RESULTS A signifi cant increase (p<0.05) of bifi dobacteria genus in faeces was observed during product consumption vs. baseline. Count decreased to baseline level 4 weeks after discontinuation of the product. In contrast, the number of bifi dobacteria genus in the positive and negative controls remained stable, over the studied period. 30% of bifi dobacteria were identifi ed as B. lactis sp. by PCR after 2 weeks of product consumption (90% after 4 weeks). Subspecies were no more detectable after 4 weeks follow-up period. 40% of bifi dobacteria were identifi ed as DN-173 010 strain by ARDRA-PCR, after 2 weeks of product consumption (90% after 4 weeks). No more detection was observed after 4 weeks follow-up period.
CONCLUSIONAfter daily consumption of 250ml of Activia® over 4 weeks, B. animalis sp. lactis DN-173 010 survived passage through the gastrointestinal tract.
TOTAL BIFIDOBACTERIA GENUS COUNTS AFTER CONSUMPTION OF ACTIVIA®
p<0.05
FISH counts Bif662 Plate counts BFM agar
FIS
H c
ount
s (lo
g ce
lls/m
l)
Pla
te c
ount
s (L
og C
FU/m
l)
Control period
Consumption period Follow-up periodSampling
12
10
8
6
4
2
0
12
10
8
6
4
2
02 3 4 51 6 7 8 9
COLLADO et al., 2006Collado M.C, Moreno Y, Cobo J.M, Mateos J.A, Hernández M. Molecular detection of Bifi dobacterium animalis DN-173 010 in human feces during fermented milk administration. Food Research International, 2006; 39: 530-535.
PDF ACTIVIA.indd 27 15/11/12 13:52
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
PDF ACTIVIA.indd 28 15/11/12 13:52
AC
TIVI
A® M
EC
HA
NIS
M O
F A
CTI
ON
STU
DIE
S: S
TRA
IN S
UR
VIV
AL
& G
UT
MIC
RO
BIO
TA M
OD
ULA
TIO
N
STUDY METHODOLOGYIn this non randomized, non controlled, open study, 5 healthy women, (20-48 yo), consumed daily 3x125g servings of Activia® over 7 days.
DUEZ et al., 2000Duez H, Pelletier C, Cools S, Aissi E, Cayuela C, Gavini F, Bouquelet S, Neut C, Mengaud J. A colony immunoblotting method for quatitative detection of a Bifi dobacterium animalis probiotic strain in human faeces. Journal of Applied Microbiology, 2000; 88:1019-27.
EVALUATION CRITERIAEvaluation at baseline and after 7 days of product consumption of human fecal samples:
Quantifi cation of Bifi dobacterium genus (Beeren’s agar pH 5, not including B. animalis sp. lactis
specie).
Quantifi cation of B. animalis sp. lactis specie (Beeren’s agar pH 5.5, specifi c to the specie).
Quantifi cation of several B. animalis sp. lactis strains such as DN-173 010 strain (immunoblotting method specifi c to strains).
RESULTSNo colonies of B. lactis were detected in any of the fecal samples before ingestion of Activia®. After 7 days of Activia® consumption, B. lactis count varied amongst subjects, between 108 and 109 CFU/g.
Popu
latio
n (lo
g C
FU/g
)
12
10
8
6
4
2
0
Subject 1 Subject 2 Subject 3 Subject 4 Subject 5
n=5
Bifi dobacteria without B. lactis (before/after Activia® ingestion), based on Bereen’s agar pH 5 method
Bifi dobacterium animalis sp. lactis (before/after Activia® ingestion), based on Beeren’s agar pH 5.5 and immunoblotting methods
ENUMERATION OF BIFIDOBACTERIA AND Bifi dobacterium animalis sp. lactis POPULATION IN FECAL SAMPLES OF FIVE HUMAN VOLUNTEERS
BEFORE AND AFTER ONE WEEK INGESTION OF ACTIVIA®
Before/after consumption of Activia®
CONCLUSIONAfter daily consumption of 3x125g servings of Activia® during one week, B. lactis DN-173 010 was found to be viable, in large quantities (≥108 CFU/g), in faeces.
PDF ACTIVIA.indd 29 15/11/12 13:52
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
PDF ACTIVIA.indd 30 15/11/12 13:52
AC
TIVI
A® M
EC
HA
NIS
M O
F A
CTI
ON
STU
DIE
S: S
TRA
IN S
UR
VIV
AL
& G
UT
MIC
RO
BIO
TA M
OD
ULA
TIO
N
STUDY METHODOLOGYIn this randomized, controlled, open study, 6 healthy volunteers (18-30 yo) consumed either 400g of Bifi dobacterium animalis sp. lactis DN-173 010 fermented milk or a monitored diet containing no bifi dobacteria specie.
EVALUATION CRITERIA Quantifi cation of viable bifi dobacteria reaching
the terminal ileum (enumeration by plate counting, in ileal perfusion, throughout the 8 hours of product ingestion).
FLOW RATE OF BIFIDOBACTERIA THROUGH THE ILEUM AFTER INGESTION OF B. lactis DN-173 010 FERMENTED MILK OR CONTROL MEAL
Control meal
B. lactis DN-173 010 fermented milk
n=6
Log 10
bac
teria
/hou
r
Time (hours)
9
8
7
6
5
4
3
2
0 2 4 6 8
RESULTSIn the control group, no modifi cation of the fl ow of bifi dobacteria was observed, and the concentration of viable bifi dobacteria throughout the experiment remained low (1.6x105 CFU/L). In the B. lactis DN-173 010 fermented milk group, a signifi cant increase in the ileal fl ow of bifi dobacteria was observed within one hour in all subjects, and a peak fl ow (6.3x108 CFU/hour), corresponding to a concentration of 2.5x109 CFU/L in the ileal fl uid, was observed, after 1.7 ± 0.4 hours. The mean number of bifi dobacteria recovered was signifi cantly smaller than the amounts ingested (109 CFU vs. 1010 CFU, p<0.02).
POCHART et al., 1992Pochart P, Marteau P, Bouhnik Y, Goderel I, Bourlioux P, Rambaud J.C. Survival of Bifi dobacteria ingested via fermented milk during their passage through the human small intestine: an in vivo study using intestinal perfusion. American Journal of Clinical Nutrition, 1992; 55:78-80.
CONCLUSION After consumption of 400g of B. lactis DN-173 010 fermented milk, ileal fl ow of bifi dobacteria increased signifi cantly. After 8 hours, 109 CFU of the strain was recovered in the terminal ileum, indicating that a large quantity of ingested bifi dobacteria reached the colon.
PDF ACTIVIA.indd 31 15/11/12 13:52
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
PDF ACTIVIA.indd 32 15/11/12 13:52
AC
TIVI
A® M
EC
HA
NIS
M O
F A
CTI
ON
STU
DIE
S: S
TRA
IN S
UR
VIV
AL
& G
UT
MIC
RO
BIO
TA M
OD
ULA
TIO
N
STUDY METHODOLOGYThe study was a randomized, controlled, double-blind, cross-over trial. Both in vivo survival (A) and gastric emptying rate (B) were studied. A: 10 healthy volunteers (20-45 yo) received 250g of either Activia® or a control product (another commercial Bifi dobacterium fermented milk). B:12 healthy volunteers (22-25 yo) received 250ml of either Activia® or a control product (another commercial Bifi dobacterium fermented milk).
EVALUATION CRITERIA A group: Survival of bifi dobacterium strains
(Samples collected using a gastric tube immediately and 30, 60 and 90 minutes after ingestion; enumeration by plate counting).
B group: Gastric emptying rate (detection of 99m-Tc-technetium-labelled solution of rhenium sulfur colloids incorporated in ingested fermented milk, by Scintigraphy, every 10 minutes, over 3 hours).
RESULTS After 90 minutes of gastric transit, Bifi dobacterium population in Activia® decreased by less than 2 log units. Bifi dobacterium population in the control product decreased by 4 log units. The difference between the survival of Bifi dobacterium strains was signifi cant (p<0.001).
There was no signifi cant difference in gastric emptying between Activia® and the control product.
CONCLUSIONAfter consumption of 250g of Activia®, Bifi dobacterium lactis DN-173 010 was able to survive gastric transit.
BERRADA et al., 1991Berrada N, Lemeland J.F, Laroche G, Thouvenot P, Piaia M. Bifi dobacterium from fermented milks: Survival during gastric transit. Journal of Dairy Science, 1991; 74:409-413.
PDF ACTIVIA.indd 33 15/11/12 13:52
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
....
..................................................................................................................................................................................................................................................................................................................................................................................................................................................
PDF ACTIVIA.indd 34 15/11/12 13:52
............................................................................................................................................................................................................................
.............................................................................................................................................................................................................................
..........................................................................................................................................................................................................................................................................................................................
............................................................................................................................................................................................................................
..........................................................................................................................................................................................................................................................................................................................
............................................................................................................................................................................................................................
.............................................................................................................................................................................................................................
..........................................................................................................................................................................................................................................................................................................................
.............................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
............................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
............................................................................................................................................................................................................................
.............................................................................................................................................................................................................................
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
..
.............................................................................................................................................................................................................................
Dan
one
2012
©In
form
atio
n fo
r h
ealth
care
pro
fess
iona
ls a
nd s
cien
tists
onl
y
PDF ACTIVIA.indd 35 15/11/12 13:52
![Lauro Trevisan[1].-.Porque.é.que.as.pessoas.felizes.são.felizes](https://img.dokumen.tips/doc/110x75/5571fbea4979599169961886/lauro-trevisan1-porqueequeaspessoasfelizessaofelizes.jpg)
