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Philippe Langella: "Commensal Bacteria and Recombinant Lactic Acid Bacteria as Novel Probiotics for Human Intestinal Health"
 

Philippe Langella: "Commensal Bacteria and Recombinant Lactic Acid Bacteria as Novel Probiotics for Human Intestinal Health"

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The first part of my talk will be devoted to the exploration the human intestinal microbiota and all the efforts developed today for its exhaustive analysis. will lead to the isolation of novel ...

The first part of my talk will be devoted to the exploration the human intestinal microbiota and all the efforts developed today for its exhaustive analysis. will lead to the isolation of novel beneficial bacteria. This aspect will be illustrated by Faecalibacterium prausnitzii which is the first anti-inflammatory commensal bacterium that we identified based on human clinical data and not via a routine usual screening (1). The second part of my talk will be focussed on the prophylactic and curative possibilities offered by genetically engineered probiotics especially to deliver anti-inflammatory molecules at the mucosal level. I will particularly describe the results obtained with the delivery of antiproteases by recLAB in colitis murine models (2).
References.

1. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottière HM, Doré J, Marteau P, Seksik P, Langella P. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16731-6.

2. Motta JP, Bermúdez-Humarán LG, Deraison C, Martin L, Rolland C, Rousset P, Boue J, Dietrich G, Chapman K, Kharrat P, Vinel JP, Alric L, Mas E, Sallenave JM, Langella P, Vergnolle N. Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis. Sci Transl Med. 2012 Oct 31;4(158):158ra144.

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    Philippe Langella: "Commensal Bacteria and Recombinant Lactic Acid Bacteria as Novel Probiotics for Human Intestinal Health" Philippe Langella: "Commensal Bacteria and Recombinant Lactic Acid Bacteria as Novel Probiotics for Human Intestinal Health" Presentation Transcript

    • Commensal Bacteria and RecombinantLactic Acid Bacteria as Novel Probiotics for Human Intestinal Health Philippe Langella Laboratory of “Commensals and Probiotics-Host Interactions” MICALIS Institute, INRA 78352 Jouy en Josas FRANCE Barcelona, Val dHebron, December 3, 2012
    • OutlineI. Faecalibacterium prausnitzii story• Part I: F. prausnitzii as an anti-inflammatory commensal bacterium• Part II: F. prausnitzii and its crosstalk with the hostII. Elafin bugs story• Part I: Unbalance proteases-antiproteases in IBD• Part II: Use of recombinant LABConclusions-perpectives Barcelona, Val dHebron, December 3, 2012
    • I. Faecalibacterium prausnitzii story • Part I: Identification of Faecalibacterium prausnitzii as an anti-inflammatory commensal bacterium • Part II: Characterization of F. prausnitzii and its crosstalk with the host • Conclusions-perspectives Barcelona, Val dHebron, December 3, 2012
    • The human intestinal microbiota 1014 microorganisms; 10 times the number of cells in human body and 100-fold more genes than in human genome Acting at interfaces between food and epithelium A true organ, most often « protecting our health and well-being throughout all stages of our life » Barcelona, Val dHebron, December 3, 2012
    • The human intestinal microbiota is composed of two major phyla Bacteroidetes Gram-negatives 10-30% Estoma c Bacteroides-Prevotella group 8.5-28%Duodénum Jéjunum / Akkermansia group Iléon Enterobacteriacaea 1.3%Côlon 0.1-0.2% Haut GC Gram-positives Clostridium leptum group Atopobium group 21.1-25.2% 3.1-11.9% 8-17% Clostridium coccoides- Bifidobacterium Eubacterium rectale group 4.4-4.8% 22.7-28% Phascolarctobacterium group Veillonella group0.6% Eubacterium cylindroides group <0.1-1.3% 1.1-1.4% Lactobacillus-Enterococcus group Firmicutes <0.1-1.8% Bas GC Gram-positives 46-58% Turnbaugh et al., 2008 Barcelona, Val dHebron, December 3, 2012
    • Dysbiosis: compositionalchanges of the microbiotaUnbalance between positive and negative bacteria Barcelona, Val dHebron, December 3, 2012
    • Dysbiosis of intestinal microbiota as a possible disease factorCrohn’s disease Seksik et al, 2003; Sokol et al, 2006, 2008, 2009; Dicksved et al, 2008; Willing et al, 2009Ulcerative colitis Sokol et al., 2008; Martinez et al., 2008Pouchitis Lim et al., 2009, Kühbacher et al., 2006Behaviour Bercik et al, 2011, Gareau et al, 2011Obesity Ley et al., 2007; Kalliomäki et al., 2008Type-2 diabetes Cani and Delzenne, 2009Type-1 diabetes Dessein et al., 2009; Wen et al., 2008Coeliac disease Nadal et al., 2007; Collado et al., 2009Allergy Kirjavainen et al., 2002; Björkstén, 2009Autism Finegold et al., 2002; Paracho et al., 2005Colorectal cancer Mai et al., 2007; Scanlan et al., 2008HIV infection Gori et al., 2008Frailty in seniors Van Tongeren et al., 2005AAD Beaugerie et Petit, 2004 (* Indications from animal models, effects of antibiotics or probiotics, clinical studies; courtesy of Joël Doré) Barcelona, Val dHebron, December 3, 2012
    • 2006: first clue ofF. prausnitzii deficiency in IBD patients 120 CD Infectious Colitis FISH UC No colitis control 100 80 60 40 20 0 Sokol et al. IBD, 2006 C. leptum Firmicutes  low proportions of C. leptum (F. prausnitzii) in CD  low proportions of Firmicutes in both CD and UC Barcelona, Val dHebron, December 3, 2012
    • F. prausnitzii deficiency confirmed in IBD patients qPCR Self limited colitis (n=8) Active IBD (n= 35 , 22 Crohn and 13 UC) 12,00 IBD in remission (n= 14 , 10 Crohn and 4 UC) Healthy subjects (n=27) 11,50 * * 11,00 * 10,50Log10 CFU/g 10,00 9,50 9,00 8,50 8,00 7,50 7,00 Bacteria Bacteroides Firmicutes F. prausnitzii Barcelona, Val dHebron, December 3, 2012 Sokol et al. IBD 2009
    • 20 patients with active ileal CD requiring an ileo-caecal resection M0 M6 Surgical resection coloscospy Remission or Endoscopic recurrence Biopsies analysis by FISH • Eub338 (Eubacteria) • Bac303 (Bacteroides-Prevotella) • Ent1458 (Enterobacteria) F. prausnitzii at M0 • Erec482 (Clostridium coccoides) 3,3% 3,4  Remission at M6• Lab158 (Lactobacillus-Enterococcus) vs • Bif164 (Bifidobacterium) 0,3% 0,5  Recurrence at M6 • Fprau645 (F. prausnitzii) (p=0.03) Barcelona, Val dHebron, December 3, 2012
    • Low level of F. prausnitzii is associated with higher risk of postoperative recurrence of Crohn’s disease Sokol. et al., 2008Anti-inflammatory effects of F. prausnitzii? Barcelona, Val dHebron, December 3, 2012
    • Who is Faecalibacterium prausnitzii?A2-165 strain - Scanning  GRAM + bacilli Electron Microscopy  Member of phylogenetic core  Major member of Clostridium leptum group  Butyrate producer  Extremely O2 Sensitive  Not transformable 1 µm Duncan et al., 2002 (Platform MIMA 2, INRA, T. Meylheuc) Qin et al., 2010 Barcelona, Val dHebron, December 3, 2012 Tap et al., 2009
    • F. prausnitzii, a member of the shared phylogenetic core57 species present in 90% 18 species present in 100%of subjects of subjects Faecalibacterium prausnitzii SL3 3 Roseburia intestinalis M50 1 Bacteroides vulgatus ATCC 8482 Bacteroides sp. 9_1_42FAA Ruminococcus sp SR1 5 Coprococcus comes SL7 1 Bacteroides sp. 2_1_7 Bacteriodes xylanisolvens XB1A Ruminococcus torques L2-14 Bacteroides sp. 2_2_4 Bacteroides sp. D4 Bacteroides dorei Ruminococcus obeum A2-162 Ruminococcus lactaris Bacteroides capillosus Bacteroides finegoldii Clostridium sp M62 1 Clostridium nexile Qin et al. Nature 2010
    • Oral administration of F. prausnitzii in TNBS-induced acute colitisHarry Sokol sacrifice TNBS F. prausnitzii TNBS F. prausnitzii D-5 D0 D2 sacrifice TNBS Supernatant Supernatant D-5 D0 D2 TNBS Colitis + PBS D0 D2 Eth/NaCl Colitis - PBS D0 D2 Barcelona, Val dHebron, December 3, 2012
    • F W allace sco r e 0 1 2 3 4 5 pr au sn itz IL -12 (p g / g ) ii S F. up er 200 300 400 500 600 pr na au sn ta nt it z ii S ** up er M na P ed ia * ta os nt iti ve *** co **** N nt * M eg ro P ed at l ia IL-12 os iv ** it i e ve co co nt ro N nt ro l eg at l iv e co Wallace macroscopic scores nt ro l F A m eh o sco r e IL -10 (p g / g ) 0 1 2 3 4 5 6 pr au sn F. it z 15000 20000 25000 pr ii au S sn up colonic cytokines it z er na ii ta S nt up er na ta ** M Barcelona, Val dHebron, December 3, 2012 nt P ed os ia ** it i M ve *** P ed co os ia N ** nt *** it i eg ro ve l IL-10 at co iv e N nt ro co eg at l nt ro iv e l co nt ro l Ameho histological scores(Sokol et al, PNAS, 2008) Protective effects of F. prausnitzii and its supernatant
    • Results (already cited 360 times) (Sokol et al, 2008)Barcelona, Val dHebron, December 3, 2012
    • F. prausnitzii: a bacterium involved in several dysbiosis BacteroidesIn Crohn’s disease: Peptostreptococci Coprococci Fecal flora Clostridium Escherichia coli Bifidobacterium Lactobacillus Faecalibacterium prausnitzii Swidsinski et al., 2002; Manichanh et al., 2006; Seksik et al., 2006; Sokol et al., 2009 In other intestinal diseases Irritable bowel syndrome Rajilic-Stojanovic M. et al., 2011 F. prausnitzii Colorectal cancer Balamurugan R. et al., 2008 Ulcerative colitis McLaughlin SD. et al., 2010F. prausnitzii could be considered as a sensor of intestinal health
    • And now?Three levels of study of F. prausnitzii mechanisms:1. F. prausnitzii itself:Biodiversity of F. prausnitzii speciesGenetic approach based on genomic library2. Its supernatant:Biochemical approach based on analysis of supernatant3. Its crosstalk with host:Simplified murine modelHost response Barcelona, Val dHebron, December 3, 2012
    • Strain-specific effects ? Analysis of anti-inflammatory effects of two other F. prausnitzii strains (L2-6 and M21/2) 250 HT-29 IL8 (pg/µg protéine) Caco-2 200Rebeca Martin 150 * * * 100 ** ** ** 50 0 Three first F. prausnitzii model strains have similar anti-inflammatory effects. Barcelona, Val dHebron, December 3, 2012
    • Isolation of four novel anti-inflammatory F. prausnitzii strains Isolated from feces of healthy volunteers * * * * * * * p ≤ 0.05Read-out: Decrease of IL-8 secretion by HT-29 cells inflamed with TNFa after contact with supernatants of each strain >>>> The four novel strains are all anti-inflammatory Barcelona, Val dHebron, December 3, 2012
    • Identification of metabolites involved in the anti-inflammatory effects?1. We showed that butyrate produced by F. prausnitzii played a minor role in these effects (Sokol et al, 2008)2. Searching for the main actors in the supernatant:- One candidate protein is currently analysed and patented (collaboration with S. Lavielle and P. Seksik, INSERM- APHP)- Two small soluble candidate molecules have been recently isolated (collaboration with N. Magarvey, McMaster and E. Allen-Vercoe, Univ. of Guelph, Canada) Barcelona, Val dHebron, December 3, 2012
    • Deciphering the F. prausnitzii anti-inflammatory effectsF. prausnitzii in novel colitis models? 1/ Chronic colitis in Conventional mice 2/ Acute colitis in Gnotobiotic mice
    • Chronic DNBS-induced colitis in conventional mice DNBS 2 mgDNBS 4 mg (Day 14 ) (Day 1) Recurrence DNBS period (Day 14-16)DNBS period (Day 1-3) Recovery (Day 4-7) Gavage (Day 8-17) Male C57BL6 6-8 weeks age Colitis control Negative control Bacteria Supernatant (Goblet depletion, PBS (low infiltration) (low infiltration) infiltration, erosion)F. prausnitzii has a protective role on the epithelium in a chronic DNBS-induced colitis.
    • Low-grade inflammation model DNBS 2 mgDNBS 4 mg (Day 14 ) (Day 1) Recurrence DNBS period (Day 14-16)DNBS period (Day 1-3) Recovery (Day 4-7) Gavage (Day 8-17) DNBS DNBS 1 mg 2 mg Recurrence DNBS period (3 days) DNBS period (3days) Recovery (10 days) Gavage (10 days)
    • Validation of low-grade inflammation model DNBS 2 mg DNBS 4 mg (Day 14 ) (Day 1) Recurrence DNBS period (Day 14-16) DNBS period (Day 1-3) Recovery (Day 4-7) Gavage (Day 8-17) DNBS DNBS 1 mg 2 mg Recurrence DNBS period (3 days) DNBS period (3days) Recovery (10 days) Gavage (10 days)No significant difference was observed between low DNBS-treated and untreated mice indicating absence of overt and active inflammation in the model.
    • Permeability in vivo and ex vivo FITC-Dextran Ussing chamber *** * * *** ** * p<0.05Supernatant of F. prausnitzii restores the initial permeability level decreased after DNBS challenge.
    • Colonic cytokines levels * * * * * * * * ** * F. prausnitzii seems to decrease cytokinic pattern for a lower immune response. * p<0.05
    • Objectives of the work Deciphering the F. prausnitzii anti-inflammatory effectsF. prausnitzii in novel colitis models? 1/ Chronic colitis in Conventional mice 2/ Acute colitis in Gnotobiotic mice
    • First trials to get monoxenic mice Germ free mice raised in a sterile isolatorand pre-treated by Na bicarbonate (0.2M) before gastric inoculations Inoculum  1x109 A2-165 D0 D1 D4 ≥D10 Both intragastric and intrarectal inoculations 5 mice successful colonized on 19 6 µmF. prausnitzii was implanted in only 20% of mice which is not sufficient for further experiments.
    • Dixenic mice with Escherichia coli JM105 and F. prausnitzii 1.E+11Implantation 1.E+10curves 1.E+09 CFU / g of feces 1.E+08 E. coli 1.E+07 1.E+06 1.E+05 F. prausnitzii 1.E+04 1.E+03 D0 D1 D2 D3 D9 D10 D17 D20 D28 D37 D48 The presence of a companion bacterium, during at least six days, allowed a durable and stable implantation of F. prausnitzii in the GIT to 1.3.109.
    • Why did we choose E. coli? E. coli F. prausnitzii Genome sequence JM105 A2-165 O2 sensibility Aero/anaerobic EOS Colonisation Primo-colonising ? Implication in dysbiosis of CD ↗ ↘
    • Acute TNBS-induced colitis in dixenic mice TNBS 50Protocol of TNBS-induced colitis mg/kg 48 h E. coli A2-165 Viable bacteria counts Implantation Implantation * J0 J8 4 to 6 weeksDisease Activity Index  Decrease of the Disease Activity Index in ** dixenic mice *** * p<0.05
    • Impact of F. prausnitzii on “health” scores Macroscopic scores Microscopic scores E. coli E. coli + F. prausnitzii 5 5 4 Ameho score 4Wallace score 3 3 ** ** 2 2 1 *** 1 *** 0 0 TNBS No TNBS TNBS No TNBS F. prausnitzii decreases TNBS-induced colitis scores in dixenic mice
    • Impact of F. prausnitzii on the histological scoresHES staining E. coli E. coli + F. prausnitzii No Colitis  No major histological modifications in dixenic mice compared to monoxenic ones  Decreased infiltration and Colitis erosion were observed in dixenic mice compared to monoxenic ones F. prausnitzii has a protective role on the epithelium in TNBS-induced colitis in dixenic mice
    • Decrease of F. prausnitzii levels after TNBS challengeViable counts of F. prausnitzii after TNBS-induced colitis in feces was linked tohistological and macroscopic scores F. prausnitzii E. coli Different levels of colonization in mice after induction of an acute colitis
    • Correlation between F. prausnitzii and protection levelsViable counts of F. prausnitzii after TNBS-induced colitis in feces was linked tohistological and macroscopic scores * ns ** *** (ie: Same results for Ameho scores) The colonization level of F. prausnitzii seems to be linked to the inflammation markers
    • Conclusions and perspectives 1/ New model of chronic colitis showing the protective role of F. prausnitzii with hight or low level of inflammation  F. prausnitzii GIT permeability .  F. prausnitzii impacts the cytokinic response. 2/ New gnotobiotic model to study roles of F. prausnitzii in the GIT  Protective role on the epithelium from an acute TNBS-induced colitis.  Colonization level correlated to the inflammation markers. F. prausnitzii is a marker and an actor of intestinal health - Go further on cytokines response - Implication of F. prausnitzii on tight junctionsF. prausnitzii is a good potential probiotic to prevent and to treat IBD and IBS
    • A new strategy to isolate novel probiotic bacterial strains? CLASSIC STRATEGY « DYSBIOSIS » STRATEGY Evidence of dysbiosis comparing Panel of 50 to 100 candidates the microbiota of healthy volunteers to patients Cellular and animals models Identification of 1 candidate 1-5 novel anti-inflammatory strains Cellular and animal experiments Barcelona, Val dHebron, December 3, 2012
    • Translational applications of F. prausnitzii strategy Correlation between human microbiota composition and clinical data using FISH and qPCR Identification of F. prausnitzii Use of prebiotics Use of F. prausnitzii Secreted molecule(s) and probiotics FprauXRecent advances;- 6 novel strains Use of LL-FprauX- one genomic library as a proof of- potential candidate molecules concept and novel- active in other colitis models probiotics- monoxenic and dixenic models Barcelona, Val dHebron, December 3, 2012
    • Fparis project• Financed by French Ministry of Research (2011-2014)• Objective: to develop a food supplement to prevent IBS• 2 industrial partners and 1 academic partner• Started in January 2011• Two post-docs recruited for 3 years• Hypothesis: low-grade inflammation is observed in IBS patients and dysbiosis in F. prausnitzii was observed in IBS patients (Rajilić-Stojanović et al, Gastroenterology, 2011) Barcelona, Val dHebron, December 3, 2012
    • II. Elafin bugs story• Part I: Unbalance proteases-antiproteases in IBD• Part II: Use of recombinant LAB• Conclusions-perspectives Barcelona, Val dHebron, December 3, 2012
    • GM LAB to deliver proteins of health interest (I)1. Possible induction of both mucosal and systemic immune responses2. Safe, easy to administer and low production cost Recombinant LAB Mucus layer Anti-inflammatory proteins Epithelium of small intestine Lamina propria Barcelona, Val dHebron, December 3, 2012
    • GM LAB to deliver proteins of health interest (II) Since the use of LL-TTFC by J. Wells in 1993, LAB has been used to deliver - Bacterial and viral antigens - Allergens - Cytokines - DNA vaccine - Antioxidants (for reviews see Wells J.M. & Mercenier A., 2008 and Bermudez et al, 2011)These GM lactococci and lactobacilli are - excellent « proof of concept » tools and- potential novel preventive and therapeutic tools for the future 43 Barcelona, Val dHebron, December 3, 2012
    • High proteolytic activity released at sites of inflammation in IBD patients * Proteolytic activity (mU/mg 2.25 2.00 * 1.75 1.50 tissue) 1.25 1.00 0.75 0.50 0.25 0.00 Controls CD UC CD UC Inflammed non-Inflammed (Cenac et al. J. Clin Invest. 2007 Motta et al. Gastroenterology, 2011)Culture media(1-h incubation) Barcelona, Val dHebron, December 3, 2012
    • Elastolytic balance is disrupted in IBD patientsCTR CD UC CD 20 * ** of ELAFIN mRNA in mucosal area 15 Fluorescence 50μm 10 5 0 Healthy CD UC Controls 50μm 50μm Barcelona, Val dHebron, December 3, 2012
    • GM LAB to counterbalanceproteases/antiproteases unbalance in IBD? Antiproteases Proteases Collaboration with Nathalie Vergnolle (INSERM, Toulouse) and JM Sallenave (Institut Pasteur) Barcelona, Val dHebron, December 3, 2012
    • The antiprotease elafin reduces intestinal mucosal inflammationDemonstrated in transgenic and viral studies in TNBS and DSS colitis models: C57BL/6 - MPO ELAFIN - Macroscopic scores - Microscopic scores - Proteolytic activity - Cytokines profile (Motta et al, 2011, Gastroenterology) Recombinant Adenovirus expressing ELAFIN Barcelona, Val dHebron, December 3, 2012
    • Recombinant LAB to deliver antiproteases Elafin and SLPILactococcus lactis Elafin IL-10 versusLactobacillus casei SLPI (Patent filed in January 2010; Motta et al, Science Translational Medicine, October 2012) Barcelona, Val dHebron, December 3, 2012
    • Beneficial effects of LL-elafin and SLPI? Oral daily gavage (7 days) during DSS colitis induction (5%) 5.109 bacteria /mouseLactococcus lactis Lactococcus lactis Lactococcus lactis ELAFIN SLPI IL-10 Barcelona, Val dHebron, December 3, 2012
    • Best results with LL-Elafin Trypsin-like Elastase 150 20 mU/mg proteinsU/mg proteins 15 100 10 50 ** 5 y y 0 0 Water DSS water DSS *, p<0.05 **, p<0.01 * vs PBS+DSS Ψ vs L.lactis Barcelona, Val dHebron, December 3, 2012
    • Best results with LL-Elafin Macroscopic damages **, p<0.01 MPO activity ***, p<0.001 15 * vs PBS+DSS 0.8 ** U/mg proteins *** Ψ vs L.lactis 0.6 10 ** 0.4 *** yyy 5 yyy *** yyy yyy yyy 0.2 0 0.0 Colonic wall thickness ** 0.75 *** *** yy *** water DSS yyy water DSS 0.50 mm 0.25(Patent filed in January 2010; 0.00Motta et al, 2012Science Translational Medicine) water DSS Barcelona, Val dHebron, December 3, 2012
    • Effects of LL-Elafin on the response of ECsexposed to SNs of IBD patients biopsies colon tissues Restoration of the intestinal permeability in the inflamed epithelium of IBD patients treated by LL-Elafin Barcelona, Val dHebron, December 3, 2012
    • Conclusions Antiproteases Proteases AntiproteasesProteases + recombinant LAB expressing antiproteases Barcelona, Val dHebron, December 3, 2012
    • Perspectives for GM probioticsThe future :- Construct biologically contained strains for well-designed human clinical trials- Use of probiotic bifidobacteria- Expression of anti-inflammatory molecules ofcommensal bacteria- Application to other pathologies- Good and convincing crosstalk with EFSA and thepotential users in Europe 54 Barcelona, Val dHebron, December 3, 2012
    • Our STM publication ScienceTranslationalMedicine, October 2012 Vol 4 Issue 158 158ra144 Barcelona, Val dHebron, December 3, 2012
    • Our STM publication Barcelona, Val dHebron, December 3, 2012
    • Take home messagesThe ability to modify the intestinal microbiota compositionwill guide the rational use of i) commensal bacteria as next-generation probiotics and ii) novel molecules derived fromcommensal bacteria.Mechanisms of beneficial effects of commensal beneficialbacteria should be determined and the strains bettercharacterized to get them accepted by EFSA and theconsumers.GM Lactic Acid Bacteria are at the moment promising“proof of concept” tools and could be in the future powerfultherapeutic tools. Barcelona, Val dHebron, December 3, 2012
    • Jouy en Josas Lab Langella Harry Sokol* Luis Bermudez Inserm, U538 Rebeca Martin Philippe SeksikHôpital Lariboisière Sylvie Miquel Bénédicte PigneurPhilippe Marteau Muriel Thomas Germain Trugnan Sylvie Hudault Ginette Thomas Chantal Bridonneau Farncombe Jouy Steve Collins Laura Wrzosek Premek BercikInstitut Pasteur Lille Lab Doré Elena VerduCorinne Grangette Hervé Blottière Patricia Blenner hassett Fabien Dumetz • Granted by ANR and by French Ministry of Research (FUI) • Special thanks to Harry Flint and Sylvia Duncan who provided F. prausnitzii strains Val dHebron, December 3, 2012 Barcelona,
    • Elafin story Jouy en JosasLab LangellaLuis Bermudez-HumaranPascale KharratJean-Jacques GratadouxLaurie Watterlot Inserm, ToulouseSébastien Blugeon Nathalie Vergnolle Laurence MartinCollaborations with Johannes Fruehauf (ViThera, Boston, MA) Barcelona, Val dHebron, December 3, 2012
    • Potential collaborations INRA-VHIR?- On human clinical trials using commensal or GMprobiotics- On novel probiotic strains: screening using in vitro and invivo models (conventional and gnotobiotic ones), andelucidation of their mechanisms- On commensal bacteria: identification of a candidatethrough intestinal microbiota analysis and evaluation of itsproperties using in vitro and in vivo models- On GM probiotics and heterologous proteins production:Production of candidate molecules in our platform andevaluation of the effects of the resulting strain- Jouy en Josas, November 24, 2011
    • Thanks for your attention! To contact me:philippe.langella@jouy.inra.fr Barcelona, Val dHebron, December 3, 2012