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Copyright © 2019 DuPont or its affiliates. All Rights Reserved. The DuPont Logo Oval and DuPont™ are trademarks or registered trademarks of E. I. du Pont de Nemours and Company. Samples manufactured in DuPont application laboratories may
contain allergens. The information contained herein is based on data known to DuPont or its affiliates at the time of preparation of the information and believed by them to be reliable. This is business-to-business information intended for food,
beverage and supplement producers, and is not intended for the final consumer of a finished food, beverage or supplement product. The information is provided “as is” and its use is at the recipient’s sole discretion and risk. It is the recipient’s sole
responsibility to determine the suitability and legality of its proposed use of DuPont products for its specific purposes. Information and statements herein shall not be construed as licenses to practice, or recommendations to infringe, any patents or
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INTRODUCTION:
Obesity is a top global health concern, and the gut microbiota and energy balance are interlinked. HOWARU® Shape, Bifidobacterium
animalis ssp. lactis 420 (B420™) consumed with or without fiber polydextrose (Litesse® Ultra™, LU), offers a promising candidate to be
utilized in the combat against obesity epidemic.
METHODS:
The efficacy of HOWARU ® Shape on metabolic health has been studied in preclinical cell models, mouse models and in a clinical trial (Fig 1).
PROBIOTIC Bifidobacterium animalis ssp. lactis 420™ FOR METABOLIC HEALTH
Uusitupa Henna-Maria1*, Lehtoranta Liisa1*, Maukonen Johanna1*
1DuPont Nutrition and Biosciences, Kantvik, Finland
DuPont Nutrition & Biosciences
Danisco Sweeteners Oy
Sokeriehtaantie 20
02460 KANTVIK
FINLAND
Email: [email protected]
www.dupontnutritionandhealth.com
RESULTS:
In cell model, B420™ supernatant alone (Fig 2)1,2,
but not in combination with fish oil2, was shown to
improve epithelial integrity. As intestinal barrier
function has been associated with an increasing
variety of diseases – both intestinal and systemic –
this finding led to hypothesis that HOWARU®
Shape, could benefit metabolic health via
increasing tight junction integrity.
In following diabetogenic and obesogenic mouse
models, B420™ with or without LU was shown to
reduce weight gain during HFD while sustaining the
intestinal integrity (Fig 3), reducing glucose levels
and improving insulin sensitivity3,4,5,6.
In a clinical trial, B420™ controlled body fat mass
(compared to placebo), mostly in the abdominal
region (Fig 4)7. Body fat mass results were
associated with serum zonulin levels7, supporting
the preclinical findings of B420™ enhancing the
epithelial integrity1,2,4. Further, B420™ alone and
with LU modified gut microbiota by increasing the
abundance of bacteria associated with a lean
phenotype such as Akkermansia spp.,
Christensenellaceae spp compared to baseline8.
The increase in Christensenellaceae spp was
associated to clinical outcomes (Fig 5)8.
CONCLUSIONS:
Both preclinical and clinical data suggests that
HOWARU® Shape is a strong candidate in
improving metabolic health, especially in weight
management. Through its capability to reduce
intestinal permeability and to modulate gut
microbiota composition leading possibly to
subsequential slow down of detrimental processes
associated to endotoxemia and low-grade
inflammation in obese states HOWARU® Shape
offers an exiting probiotic for weight management.
References: 1. Putaala et al. Research in Microbiology 2008; 159:69 2. Mokkala et al. Nutr Res. 2016;36(3):246; 3. Amar et al. EMBOMol Med 2011;3(9):559; 4. Stenman et al. Benef Microbes 2014;5:437; 5. Stenman et al. Diabetol Metab Syndr 2015;7:75; 6. Garidouet al. Cell Metab. 2015;22(1):100-12; 7. Stenman et al. EBioMedicine. 2016 Nov;13:190-200; 8. Hibberd et al. Benef Microbes.2019;10(2):121-135.
Fig. 1. Preclinical in vitro and animal trials as well as the clinical trials completed or ongoing with HOWARU® Shape and metabolichealth outcomes.Fig 2. B420™ supernatant improves epithelial integrity in a Caco-2 cell model.FIg3. In diabetogenic mouse model, B420™ was able to ameliorate the disruption of gut barrier integrity measured by LPS incirculation.Fig 4. In per protocol population of clinical trial HOWARU® Shape resulted in 4.5% (1.4 kg) less fat mass vs. placebo (P=0.02).Fig 5. The microbiota results of the clinical trial indicate that HOWARU® Shape modifies positively gut microbiota composition in 6months intervention, and the modifications correlate with clinical outcomes. Relative abundance (mean± SD) of Christensenellaceaefor Placebo, LU, B420 and LU+B420 groups (a). Spearman correlations between Christensenellaceae abundance and Waist hip ratio (b)and Energy intake (c) at baseline and for dual-energy X-ray absorptiometry (DXA) Android fat (d) and Trunk fat (e) after 6 mo ofintervention with LU+B420. P<0.01, **P<0.01, *P<0.05 vs Placebo, Kruskal-Wallis with Steel-Dwass post-hoc test and Benjamini-Hochberg FDR correction.
0
1
2
3
4
5
6
7
NC Control B420
a
b
a
Plasma LPS (EU/ml)
High fat,
low carb diet
• Caco-2 cells are treated with cell-free supernatants of four
probiotics including B420™ after cultivating the bacteria
anaerobically at 37 Celsius in Man, Rogosa and Sharpe (MRS)
broth supplemented with 1.0% glucose and differentiating the
Caco-2 cells by short-term differentiation protocol. Then, Caco-
2-cells were incubated for 24 hours with cell-free supernatants
of the tested strains, and TEER measurement was performed1
• In another study the impact of cell-free culture supernatant of
B420™ with and without fish oil on intestinal permeability in a
CaCo-2 cell model was studied2
Diabetogenic mouse model3:
Mice were fed a high-fat, ketogenic diet (72 energy % fat)
for 4 weeks, with a 6-week subsequent treatment with
B420™ (108-1010 cfu/day) or vehicle
Obesogenic mouse model:
C57Bl/6J mice were fed a high-fat diet (60 energy %) for 12
weeks, and gavaged daily with B420™ (109 cfu) or vehicle.
• A randomized placebo-controlled multicenter clinical trial with a 6
months intervention
• Study design and execution follows ICH-GCP
• 225 Finnish participants with BMI 28-34.9, otherwise healthy
• Primary outcome: relative change in body fat mass, Secondary and
exploratory parameters: body composition and metabolic health
outcomes, gut microbiota composition and metabolites
• Four arms: 1. Placebo, 2. B420™ (1010 cfu/day), 3. PDX (12 g), 4.
B420™ (1010 cfu/day) with LU
• Clinicaltrials.gov: NCT01978691
*Confilct of interest: All authors work at DuPont Nutrition and Biosciences.
New clinical trial
initiated 2019
Mokkala et al. Nutr Res 20162
Putaala et al Res Microbiol 20081
Amar et al. EMBO Mol Med 20113
Stenman et al. EBiomedicine 20167
Stenman et al. Diabetol Metab Synd 20155
Garidou et al. Cell Metab 20156
In preclinical in vitro models: In obesogenic and diabetogenic mouse models: In a clinical trial:
Fig 2
Fig 3
Fig 1
Fig 4
Hibberd et al. Benef Micr 20198
Stenman et al. Benef Micr 20144
Fig 5