Transcript No Slide Title

Van warmtewisselaar naar
maag-darm
kanaal
Marc Vissers & Peter de Jong
NIZO food research, Food Valley, the
Netherlands
[email protected]
[email protected]
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 1
Outline
1. Introduction to NIZO food research
2. Control of bacteria in heat treatment
equipment: a chemical engineering
approach!
3. Control of bacteria in humans: again a
chemical engineering approach?!
4. Conclusions
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 2
Introducing NIZO food
research
•
Roots (1948) in the dairy industry now leading European research
company
•
Applying knowledge for product innovations together with customers
•
Constant search for ways to improve food
•
200 professionals
•
State-of-the-art facilities & food-grade pilot plant
•
Located in “Food Valley” in The Netherlands
•
Partner in WCFS (Wageningen Centre for Food Sciences) and Kluyver
Centre for Genomics of Industrial fermentation
•
ISO 9001:2000 certified
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 3
Expertise
biopolymer
systems
dairy
processing
systems
microbial
systems
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 4
Expertise
• Enzymatic
modification
• Making and breaking
of gels and emulsions
• Making and
measuring aroma
and taste
• controlled release
biopolymer
systems
• Powder technology
• Safe and efficient
food processing
dairy
processing
systems
microbial
systems
•Health and
ingredients from
lactic acid
bacteria
•Prebiotics for
gut health
•Shelf life
•Rapid detection for
safe foods
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 5
Organisation
• Making and breaking
of gels and emulsions
Texture
• Making and
measuring aroma
and taste
• controlled release
biopolymer
systems
Processing
• Powder technology
• Safe and efficient
food processing
• Enzymatic
modification
Flavour
dairy
processing
systems
microbial
systems
•Health and
ingredients from
lactic acid
bacteria
•Prebiotics for
gut health
Food safety
Health
•Shelf life
•Rapid detection for
safe foods
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 6
The way we work …
• Dedicated Business Development Managers and Account
Managers to ensure direct communication lines
• Professional project management
• Unique teamwork of experts with industrial and academia
backgrounds
• Confidentiality is the key factor in all our processes
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 7
Track record NIZO food
research
•
A selection:
• Starter cultures (CSK Food
Enrichment)
• Process equipment (Casomatic)
• Expression systems (NICE)
• Products (various cheeses, NIZO
butter process)
• Processing models (Premia, Premic)
• Taste solutions (PeptoPro Sport at
Olympic Games 2004)
• 9 awards in 1999-2003
18,0
• Many publications in refereed journals
15,0
• Autonomous growth contract research
12,0
Contract
Research
Strategic
Research
9,0
6,0
fundamental
food research in
WCFS
3,0
0,0
1995
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 8
1996
1997
1998
1999
2000
2001
2002
2003
2. Control of bacteria in heat
treatment equipment: a chemical
engineering approach!
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 9
Problem definition
Concentration in end product as function of
runtime
Concentration (CFU/ml)
100000
10000
1000
100
10
1
0
2
4
6
Cleaning 8
Runtime (hr)
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 10
10
12
Biofilm development
• Growth
• Adherence
• Release
• (Inactivation)
cfu/ml
time
0h
2h
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 11
8h
Biofouling model
bacteria
bacteria
growth
adherence
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 12
release
It works!
ROUTE 1
exp. (c0=10 cfu/ml)
9
10
8
10
exp. (c0=10 cfu/ml)
NIZO-PCS
10
7
4
c0=10
10
c0=10
5
10
4
10
3
10
2
predicted
contamination
10
1
10
0
0
2
4
6
8
10
12
Concentration (cfu/ml)
10
6
10
4
8
c0=10
exp. (c0=10 cfu/ml)
NIZO-PCS
7
Concentration(cfu/ml)
10
4
4
10
ROUTE 2
exp. (c0=10 cfu/ml)
9
10
5
10
4
10
3
10
2
10
1
10
0
10
Operating time (h)
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 13
c0=10
6
0
2
4
6
8
Operating time (h)
10
12
NIZO Premia
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 14
3. Control of bacteria in humans:
again a chemical engineering
approach?!
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 15
Problem definition
• Gut health is affected
by the intake of
bacteria
• It is not easy to get
volunteers for testing
the impact of
pathogenic bacteria in
the gut
• Many experimental
effort (trial & error) in
rats etc.
daily intake of good
and bat bacteria
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 16
number of
active
bacteria in
the gut
(health)
Once upon a time not that long ago …….
E. coli in faeces human as a function of time
Log CFU/gr in faeces
9
8
7
6
5
4
0
Process technology
& Modeling
1
2
3
4
5
6
7
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 17
8
9
10
11
12
Time (days)
Nutrition &
gut health
Surprise, surprise
• Growth
• Adherence
• Release
• (Inactivation)
E. coli in faeces human as a function of time
Log CFU/gr in faeces
9
9,0
8
8,0
7
7,0
6
6,0
5
5,0
4
4,0
0
1
2
3
4
5
6
7
8
9
10
11
12
Time (days)
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 18
But,
What is most important ?
Is rat equal to human ?
Criticism of the
expert
•
•
•
•
Human ≠ Machine
Rat ≠ Machine
Modeling is not useful when you have data
Processes in gut are too complex
• Modeling should result in contraintuitive hypotheses!
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 19
Objectives
 increase insight in growth and adherence of
pathogen in gastrointestinal tract
 make comparison of experimental data rat of
human possible
 evolvement of (contra-intuitive) hypothesis for
observed phenomena
 evolvement of new ideas and experiments for
research projects.
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 20
Starting points
• Simplify processes in the gut to basic processes
and add necessary details later
• Mechanistic approach
– Variables related to inactivation / growht / adherence and
release
• Consider gastro-intestinal tract as a series of
chemical reactors
– Account for residence time distribution
• Focus on increasing insight and not on prediction
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 21
The model
Stomach
residence time
distribution
F
data
Small
Stomach
intestine
F
t
time
concentration
concentration
t
data
model
time
Large
Stomach
intestine
F
t
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 22
OUTPUT:
• location
• growth rate
• adherence rate
• release rate
Results – different
curves
9,5
Kinetic model constants
Small I?
Large I?
Growth
7,98E- 5 1,00E- 8
Adherence 9,90E- 7 2,30E- 7
Release
9,00E- 5 9,00E- 5
(R^2 =0,98)
9,0
Log CFU/gr in faeces
Log CFU/gr in faeces
9,5
9,0
8,5
8,0
7,5
7,0
6,5
6,0
5,5
5,0
4,5
4,0
8,5
8,0
7,5
7,0
Kinetic model constants
Small I?
Large I?
Growth
1,49E- 4 5,52E- 7
Adherence 6,10E- 8 4,45E- 8
Release
1,56E- 4 1,56E- 4
(R^2 =0,99)
6,5
6,0
0
1
2
3
4
5
6
7
Calculated
8
9
10
11
5,5
12
0
1
2
3
Measured
4
5
Calculated
20-1-2004
Salmonella in faeces rat as a function of time with Calcium
6
7
8
9
10
Measured
Proef TR9 en TR1 berekende curves en meetpunten voor experimenten met FOS
9,0
7,5
TR9 LCA FOS
Growth Adherence Release
(h-1)
(m h-1)
(h-1)
Dun 8,8 E-1 9,5 E-7
8,8 E-1
Dik <1,0 E-4 4,9 E-5
8,8 E-1
Kinetic model constants
Small I?
Large I?
Growth
8,04E- 5
1,30E- 7
Adherence 7,96E-11 1,27E-10
Release
8,34E- 5
8,34E- 5
(R^2 =0,96)
7,0
6,5
8,0
6,0
Log CFU/g
Log CFU/gr in faeces
28-1-2004
Salmonella in faeces rat as a function of time experiment
WR11
6-2-2004
E. coli in faeces human as a function of time
5,5
7,0
5,0
4,5
6,0
4,0
3,5
0
1
2
3
4
5
Calculated
6
7
8
9
10
5,0
0,0
Measured
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 23
1,0
2,0
3,0
4,0
5,0
Tijd (dag)
6,0
7,0
8,0
9,0
10,0
Compare treatments
(Salmonella in rat with
or without calcium)
Diet without calcium
Diet with calcium
16-1-2004
20-1-2004
8,5
8,5
Kinetic model constants
Small I?
Large I?
Growth
3,11E- 4
1,65E- 6
Adherence 5,23E-10
3,24E-10
Release
3,18E- 4
3,18E- 4
(R^2 =0,98)
8,0
8,0
7,5
7,0
Log CFU/gr in faeces
Log CFU/gr in faeces
7,5
Kinetic model constants
Small I?
Large I?
Growth
8,04E- 5
1,30E- 7
Adherence 7,96E-11 1,27E-10
Release
8,34E- 5
8,34E- 5
(R^2 =0,96)
6,5
6,0
5,5
5,0
7,0
6,5
6,0
5,5
5,0
4,5
4,5
4,0
4,0
3,5
3,5
0
1
2
3
4
5
Calculated
6
7
8
9
10
0
Measured
1
2
3
4
5
Calculated
6
7
Measured
Calcium mainly affect growth in small intestine
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 24
8
9
10
Compare human and rat
(E. coli)
RAT
HUMAN
21-1-2004
E. coli in faeces rat as a function of time with no additives (blanco)
6-2-2004
8,5
9,5
9,0
8,5
8,0
7,5
7,0
6,5
6,0
5,5
5,0
4,5
4,0
Kinetic model constants
Small I?
Large I?
Growth
7,98E- 5 1,00E- 8
Adherence 9,90E- 7 2,30E- 7
Release
9,00E- 5 9,00E- 5
(R^2 =0,98)
Kinetic model constants
Small I?
Large I?
Growth
1,50E- 4
1,14E- 5
Adherence 1,69E- 9
6,93E-10
Release
1,65E- 4
1,65E- 4
(R^2 =0,99)
8,0
7,5
Log CFU/gr in faeces
Log CFU/gr in faeces
E. coli in faeces human as a function of time
7,0
6,5
6,0
5,5
5,0
4,5
4,0
3,5
0
1
2
3
4
5
6
7
8
9
10
11
12
3,0
0
Calculated
Measured
1
2
3
4
5
Calculated
6
7
8
9
10
Measured
Reaction to E. coli was considered to be similar for rat and human
Adherence >> growth
Growth >> adherence
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 25
Contra-intuitive
Brot h
10
Brot h
10
Human FW
E TE C ( l og
C FU / ml )
10
E TE C ( l og
C FU / ml )
10
Human FW
Rat f w
9
8
7
6
Rat f w
9
8
7
6
0
2
4
6
Ti me ( h)
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 26
0
2
Ti me ( h)
4
6
Objectives
 increase insight in growth and adherence of
pathogen in gastrointestinal tract
 make comparison of experimental data rat of
human possible
 evolvement of (contra-intuitive) hypothesis for
observed phenomena
 evolvement of new ideas and experiments for
research projects.
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 27
4. Conclusions
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 28
Conclusions
• Application of a basic chemical-engineering
approach to the gut is possible and useful
• New insights regarding
– Growth, adherence and release in gut
– Effect treatments
– Difference human and rat
• Collaboration between disciplines:
everybody benefits
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 29
Acknowledgements
• Wageningen Centre of
Food Science
KIVI-NIRIA Optimaal gebruik van technologie in de zorg
Tuesday, July 07, 2015
slide 30