Food, GI-tract Functionality and Human Health Cluster

EU 5th framework Food, GI-tract Functionality and Human Health Cluster - experiences and

prospects

Food, GI-tract Functionality and Human Health Cluster

Cluster coordinator Prof Tiina Mattila-Sandholm

• ^{8 EU QOL}

Programme projects

• 64 research

partners from 16 European countries

• Budget 17 MEuro, EU contribution 12.4 MEuro

• Years 2001 - 2005

FP5 Example:

PRO-EU-HEALTH Cluster

MICROBE DIAGNOSTIC

PROTECH

CROWNALIFE

DEPROHEALTH

PROGID

EU-MICRO FUNCTION

PROSAFE PROPATH

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Safety of probiotic bacteria Probiotic - prebiotic technology

Why are probiotics effective?

Probiotic against pathogens A healthier retirement

Second generation probiotics

New therapeutics with potential against IBD Which bacterium

is which?

Development and application of high

throughput molecular methods for studying the human gut microbiota in relation to diet and health (MICROBE DIAGNOSTICS, QLK1- 2000-00108)

• development and application of advanced automated molecular

methods for monitoring responses of human gut microbiota composition and gene expression

• identification of links between intestinal dysfunctions, intestinal

bacteria, to mechanisms underlying the relationships between diet, life style, intestinal bacteria and optimal health

HIGHLIGHT RESULTS: MICROBE DIAGNOSTICS

Project Co-ordinator: Prof. Michael Blaut ([email protected]) 1) Improved coverage of biodiversity of human gut microbiota

• Isolation of 800 fecal strains, 70 isolates did not correspond to described species, 22 novel species

• Over 1000 fecal 16S rRNA clones have been analyzed

• Web site of GI-tract diversity:

www.food.rdg.ac.uk/people/afs99pal/index.htm

2) Culture-independent automated enumeration of faecal bacteria

• Improved protocols for microscopical sample preparation, image capture and image analysis

• Further development of high throughput DNA-microarrays, 4169 probes (~1000 bacteria) will soon be printed on a microarray

Design of new probiotics as biotherapeutic agents or vaccine delivery vehicles.

Two types of intestinal

diseases will be targeted in this project:

1. Inflammations such as inflammatory bowel disease (IBD)

2. Infections such as those caused by rotavirus and Helicobacter pylori

Probiotic strains with designed health

properties (DEPROHEALTH, QLK 1-

2000-00146)

HIGHLIGHT RESULTS: DEPROHEALTH

Project Co-ordinator: Dr. Annick Mercenier ([email protected])

• Cell wall mutants with strikingly enhanced immune modulation capacity were constructed in the target strain Lactobacillus plantarum

• Oral administration of Lactococcus lactis secreting mlL10 prevents and heals chronic colitis in three different mouse models

• Biocontained L. lactis secreting hlL10 does not survive in the environment and was approved by a Dutch ethical committee for physically contained clinical trial in 12 Crohn’s disease patients

• Prototype recombinant Lactobacillus strains partially protecting mice against Helicobacter or rotavirus infections have been designed

• Evidence that probiotics may have a role in maintaining remission of IBD

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populations as causative or contributory agents of IBD

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population of the role of functional foods in maintaining a healthy lifestyle

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Probiotics and gastrointestinal disorders - controlled trials of

European Union patients (PROGID, QLK1-2000-00563)

HIGHLIGHT RESULTS

PROGID

Project Co-ordinator: Prof. Fergus Shanahan ([email protected])

• The effect of Lactobacillus salivarius and Bifidobacterium infantis to help maintain remission in ulcerative colitis and Crohn’s disease has been studied

- Clinical studies on have been completed and analysis of the data is in progress

• Molecular techniques revealed substantial temporal variation in the faecal microbiota of ulcerative colitis patients relative to

healthy persons

• The microbiota of patients who remained in remission appeared to be stabilising later in the trial

1. Does the human gut

microflora alter with age in adults of different countries from Southern to Northern Europe?

2. Do changes in composition of the gut microbiota correlate with functional alterations in gut microbiota with

implications for health?

3. Can age-related alterations of the structure and functions of the microbiota be modified by diet?

Functional foods, gut microflora and healthy

ageing (CROWNALIFE, QLK1-2000-00067)

HIGHLIGHT RESULTS

CROWNALIFE

Project Co-ordinator: Dr. Joël Doré ([email protected])

Characterization of the fecal microbiota of the elderly:

• Increased bacterial diversity with age: totally new clusters/species have been identified (incl. bifidobacteria and lactobacilli)

• Baseline study of microbiota composition and function with 240 subjects is finished: marked inter-country differences in the composition and

function of microbiota was detected

• Intervention study with B. animalis DN-173010 and raftilose Synergy 1:

- the probiotic utilised raftilose and survived the GI-transit

- the synbiotic promoted higher numbers of bifidobacteria in the elderly (N= 55)

- functional modulation of microbiota is currently under assessment

Nutritional enhancement of probiotics and prebiotics: technology aspects on microbial viability, stability, functionality and on prebiotic function (PROTECH, QLK1-2000-00042)

• effects of processing on probiotics

⇒ development of optimal process and formulation technologies to maintain the stability and

functionality of probiotics

• application of new processing techniques applied to the

development of functionally

enhanced prebiotics and synbiotic combinations

HIGHLIGHT RESULTS: PROTECH

Project Co-ordinator: Prof. Dietrich Knorr (Dietrich.Knorr@TU- Berlin.de)

1. Viability and stability of probiotic bacteria is strain specific and propagating and down-stream processing steps

should be tailor-made for each strain

2. Processing conditions, packaging material and storage conditions all have an impact whether the probiotic

bacteria will survive in the product

3. Treatments such as stress-treatments can be utilized to improve the viability of the strains (so far tested in pilot- scale – it is possible to perform this in an industrial scale too)

Molecular Analysis and Mechanistic Elucidation of the

Functionality of Probiotics and Prebioties in the Inhibition of Pathogenic Microorganisms to Combat Gastrointestinal

Disorders and to Improve Human Health (PROPATH, QLK200001179)

• inhibition of Gram-negative pathogenic bacteria Salmonella, and Helicobacter pylori by probiotics

• identification of compounds, and mechanism of the inhibition

HIGHLIGHT RESULTS: PROPATH

Project Co-ordinator: Prof. Luc De Vuyst ([email protected]) 1) Helicobacter pylori SS1 infection mouse model

• The gastritis scores in both chronic gastritis (inflammation of the stomach) or chronic active gastritis were reduced after consumption of probiotics although no difference was observed in H. pylori gastric sample colonisation

• The probiotic effect was strain specific (Lactobacillus johnsonii La1 had the most prominent effect)

2) L. johnsonii La1 produced protease-sensitive compounds inhibitory to both lactobacilli and H. pylori

3) Salmonella enterica ser. Typhimurium SL 1344 infection mouse model

• The levels of Salmonella in the tissues and the gut contents were reduced after consumption of probiotics for seven days.

• Lactobacillus casei Shirota and Lactobacillus fermentum ACA-DC 179 had the most significant effect.

4) Certain lactobacilli produced antibacterial compounds that have a strong killing effect towards S. enterica ser. Typhimurium SL 1344 and inhibit the invasion of Salmonella into human cultured epithelial intestinal cells.

Functional assessment of interactions between the human gut microbiota and

the host (EU AND MICROFUNCTION, QLRT-2001-00135)

• effects of probiotics, prebiotics, synbiotics on the human gut

microflora and gastrointestinal function

• mechanisms involved in the

functionality through novel model systems and newly developed

molecular-based techniques

HIGHLIGHT RESULTS: EU & MICROFUNCTION

Project Co-ordinator: Prof. Glenn R. Gibson ([email protected])

• Prebiotic comparisons in 3 stage continuous culture gut model studies are complete

• Probiotics, prebiotics and synbiotics seem to confer varying levels of

protection against translocation in 2 different animal models – a human trial is ongoing

• Various synbiotics were seen to increase populations of bifidobacteria in batch and continuous (3 stage) culture model systems of the gut

• The interaction between a novel mucin degrading bacterium and in vitro model human intestinal cell lines was determined. The microorganism could induce a response after 2 hours by inducing IL-8 and MUC 3 genes

• A pilot human trial completed in Estonia on various indices of gut health in response to probiotics, has been completed and a larger trial about to

commence

• Experimental animal models are ongoing with probiotics in healthy rats, rats with naturally infected Helicobacter spp., and rats with experimentally-induced colitis

• biosafety of probiotic bacteria (e.g lactobacilli, lactococci, enterococci, and bifidobacteria)

• taxonomic description, detection of resistance genes and virulence

properties

• immunological adverse effects, survival, colonisation and genetic stability of probiotics in the human gut

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Biosafety evaluation of probiotic lactic acid bacteria used for human consumption (PROSAFE,

QLK-2000-01273)

HIGHLIGHT RESULTS: PROSAFE

Project Co-ordinator: Prof. Herman Goossens ([email protected])

• Completion of database on safety of lactic acid bacteria (LAB) and bifidobacteria

• Establishment of the final PROSAFE LAB collection: 835 strains (279 nutritional, including 243 probiotic strains; 540 human)

• Identification, typing and antibiotic susceptibility testing of all strains completed

• Adhesion experiments of the strains completed

• In vivo virulence testing of the strains ongoing

Cluster Coordinators

Prof. Fergus Shanahan UCC, IE

Prof. Glenn Gibson

University of Reading, UK

Prof. Dietrich Knorr TUB, Germany

Dr. Joel Dore INRA, FR

Dr. Annick Mercenier Nestec, CH

Prof. Luc de Vuyst

VUB, B Prof. Michael Blaut DIFE, Germany

Prof. Herman Goossens University of Antwerp,

Belgium

SCIENCE PLATFORM

Scientific audience,

Prof. Willem de Vos Wageningen

University, The Netherlands

INDUSTRY PLATFORM

Commercial audience, Prof. Charles Daly

UCC, Ireland

CONSUMER PLATFORM

Consumer audience,

Dr. Liisa Lähteenmäki VTT, Finland

Three platforms will disseminate the aims and findings of the cluster to targeted audiences.

SCIENCE PLATFORM: INDUSTRY PLATFORM: CONSUMER PLATFORM:

•to find out mechanisms behind health effects on molecular level

•to develop new tools for R&D

•to characterize and explore the unknown microbiota of the GI- tract

•to find the products which have real clinical/scientific credibility within the jungle markets

•most of the consumers are within healthy population

•dose-response information and daily dose requirements

•to produce products for large population groups for daily use

•probiotic effects are based against diseases of the gut

•research on mechanistic effects risky, expensive

•scientific breakthroughs cannot be achieved fast nor with low-cost

2nd ProEUHealth Workshop 2-5 March 2003

Taormina, Italy

3rd ProEUHealth Workshop 13-17 March 2004

Sitges, Spain Brussels 2003, industry

meeting

4th ProEUHealth

Workshop, 10-11 March 2005, Brussels

The cluster pros and cons

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