The primary shield: role of our microbes in heath and diseases

The primary shield: role of our microbes in heath and diseases


>>GOOD AFTERNOON. THANK YOU VERY MUCH FOR ATTENDING THIS DYER LECTURE. I AM STEVE HOLLAND, THE SCIENTIFIC DIRECTOR OF NIAID AND IT GIVES ME IMMENSE PROFESSIONAL AND PERSONAL PLEASURE TO HAVE A CHANCE TO INTRODUCE TODAY’S SPEAKER. BEFORE I DO, I’D LIKE TO SHOW ONE SLIDE TO REMIND US OF WHO ROLLA DYER WAS. AND ROLLA DYER, AS YOU CAN NOT SEE HERE, WAS BORN IN 1886 IN DELAWARE COUNTY, OHIO. WENT FROM THERE TO KENYON COLLEGE IN OHIO, THEN WENT TO THE UNIVERSITY OF TEXAS FOR HIS MD DEGREE. BUT THINGS DIDN’T GET GOOD FOR HIM UNTIL HE JOINS THE U.S. PHS IN 1916. THEN MOVED ON TO THE PRECURSOR FOR THE NATIONAL INSTITUTES OF HEALTH. IN 1936 BECAME CHIEF OF THE DIVISION OF DISEASES. YOU HEAR A THEME HERE. AND BECAME ABSOLUTELY INTEGRAL IN THE DISCOVERY OF NOT ONLY ENDEMIC TYPHUS, BUT THE DEVELOPMENT OF VACCINES AGAINST IT. FROM 1942 TO 1950 WAS DIRECTOR OF THE NATIONAL INSTITUTE OF HEALTH. A POSITION NEVER HELD IN AGAIN. 1950 IT BECAME THE NATIONAL INSTITUTES OF HEALTH. HE WAS INVOLVED IN THE PLANNING OF THE CLINICAL CENTER. HE WAS THE RECIPIENT OF NUMEROUS AWARDS INCLUDING THE LAST REWARD, AND WAS ONE OF THE VERY FIRST IN 1957 TO WE INVOLVED IN THE PUBLICATION OF OBSERVATIONS MAKING IT CLEAR THAT CIGARETTE SMOKIS WAS LINKED TO LUNG CANCER. DR. DYER IS THE EFFICIENT CAUSE FOR THE PERSON WE ARE HERE TO HONOR AND TO HEAR FROM TODAY. DR. YASMINE BELKAID, BORN IN ALGIERS, GOT HER BS AND MASTER’S DEGREES THERE AT THE INSTITUTE OF ALGERIA. EN WENT TO PARIS IN 1996 WHERE SHE RECEIVED HER Ph.D. WITH DISTINCTION IN SEARCH OF REAL CUISINE. SHE CAME TO THE UNITED STATES TO JOIN THE LABORATORY OF SIOLOGY, STUDIED FOR 6 YEARS BEFORE TAKING A SOJOURN TO CINCINNATI IN SEARCH OF REALLY THE COUNTRY’S BEST CHILLY. AND WAS EXTREMELY SUCCESSFUL THERE BUT REALIZED THAT THE STUDY OF PARATOLOGY AND IMMUNOLOGY WAS INCOMPLETE ABOUT THE STUDY OF THE MICROBES THAT DROVE CHRONIC INFLAMMATORY AND EXPOSURE TO THE ENVIRONMENT. SO SHE CAME BACK HERE IN 2005 TO BECOME THE HEAD OF [INDISCERNIBLE] IMMUNOLOGY UNIT, THEN SECTION IN THE LABORATORY OF PARASITIC DISEASES. IN 2014, RECOGNIZING THAT THE MONEY WAS AN ESSENTIAL PART OF HOW WE DO THINGS, SHE CAME THE DIRECTOR OF THE MICROBIOME PROGRAM, AND HAS CONTINUED TO LEAD THAT AS WELL AS MANY OTHER THINGS TO THIS DAY. THERE ARE, I’M SURE A FEW THINGS THAT SHE HAS NOT BEEN HONORED FOR AND DIRECTED, ALTHOUGH I COULD NOT FIND THEM FOR THIS. SO I’LL REMIND YOU SHE IS ON THE EDITORIAL BOARDS OF THE JOURNAL OF EXPERIMENTAL MEDICINE, CELL, AND SCIENCE. AND THE RECENT, I’M ONLY LISTING THE LAST 2 YEARS OF AWARDS IN 71 IS NOT FAR ALONG — 2017 IS NOT FAR ALONG, THE AAI THERMAL FISHER AWARD [INDISCERNIBLE] AND THE INSTITUTE PAST MUCH AWARD. SHE IS INTERNATIONALLY RECOGNIZED LEADER IN THE FIELD, MORE IMPORTANTLY, A LOCALLY RECOGNIZED LEADER AND MENTOR TO YOUNG AND OLD SCIENTISTS ALIKE. DIVERSITIES ME GREAT PLEASURE TO INTRODUCE DR. YASMINE BELKAID.>>THANK YOU VERY MUCH FOR THE KIND INTRODUCTION. I HAVEN’T FOUND THE PERFECT CAN YOU SEEN BUT I FOUND THE NIH. IT’S AN HONOR TO BE HERE IN THE NAME OF SOMEONE WHO HAS MADE SUCH AN IMPORTANT NAME IN DISEASE. THIS IS DISCUSSING SOME OF THE UNDERSTANDING OF THE CROSS TALK IN THE MICROBIOME PATHOGEN AND THE WORK WE HAVE DONE IN THE LAST FEW YEARS AT THE NIH. SO MANY OF YOU DO KNOW BY NOW THAT WE ARE COLONIZED VERY SOON AFTER BIRTH. PRESENT AT EVERY SINGLE SURFACE, AND IT’S BELIEVED THAT THE NUMBER OF THESE ARE [INDISCERNIBLE] THAN THE NUMBER OF HUMAN CELLS. THE GENES EXPRESSED BY THESE MICROBES IS LIKELY 100 TIMES MORE THAN OTHER OWN GENOME. THE IDEA THAT WE LIVE WITH MICROBE IS NOT A NEW CONCEPT. IN THE 17th CENTURY, A DUTCH SCIENTIST THAT WAS BELIEVED TO BE THE HEAD AND FATHER, NOT THE HEAD, OF MICROSCOPY DISCOVERY WAS THE FIRST ONE TO OBSERVE MICROBES IN HIS OWN SALIVA. HE SEVERED TO THEM IN THESE POETIC TERMS. I’M NOT GOING TO TRY TO SAY THESE SENTENCES. THE CONCEPT IS NOT ONLY A NEW CONCEPT. THIS PHYSICIAN WAS THE FIRST ONE TO LINK PROLONGED LIFE WITH THE IDEA OF FERMENTED PRODUCT. IN THE SENSE OF RESEARCH, A VERY IMPORTANT GERMAN SCIENTIST UNDER COVERED A VERY IMPORTANT PRINCIPAL OF HEALTH DISCOVERING [INDISCERNIBLE], IMPORTANT GATEKEEPER OF THE HEALTH OF THE VAGINAL ENVIRONMENT AND PREVENTED AGAINST INFECTION. SO THIS ACTUALLY LED TO MANY, MANY YEARS OF DISCOVERY LINKED TO HUMAN HEALTH. OVER THE LAST TEN YEARS, THIS FIELD REEMERGED BECAUSE OF THE NEW EMERGENCE OF TECHNOLOGY THAT REALLY ALLOWED THE EXPLORATION OF THESE MICROBES WITH UNPRECEDENTED LEVEL OF DEPTH. THIS ALLOWED THE SCIENTIFIC COMMUNITY TO EXPLORE AND FIND A LINK BETWEEN MICROBE AND EVERY ASPECT OF HOST PHYSIOLOGY. OF COURSE THIS FUNDAMENTAL FOR THE CONTROL OF DIGESTION, FOR VIM SIN THEY SAYS, THE METABOLISM OF HORMONES BUT ALSO A ROLE IN THE CONTROL OF METABOLISM. THIS MICROBES HAVE BEEN SHOWN TO BE IMPORTANT FOR THE CONTROL OF THE NERVOUS SYSTEM. THERE IS LITERATURE THAT LINKED THE BIOSECURITY TO BEHAVIOR — MICROBIOTA. TO BEHAVIOR AND FUNCTION. THIS IS ONE OF THE AREAS OF RESEARCH WE HAVE EXTENDED OVER THE LAST FEW YEARS. THIS ACTUALLY HIGHLIGHTED THE FACT WHEN THAT THESE MIRES ARE EXTREMELY IMPORTANT IN THE IMMUNE SYSTEM. NOT THE LEVEL OF THE SITE IN WITH ETHER PRESENT. BUT ALSO DISTALE. SO OVER THE LAST FEW YEARS, WE AND MANY OTHERS HAVE DONE WORK THAT LINKED THE MICROBIOTA TO THE CONTROL OF EVERY ASPECT OF THE HUMAN SYSTEM. THE HUMAN SYSTEM DEVELOPMENT, FOR INSTANCE, IS DEPENDENT ON THE MICROBIOTA TO HAVE FORMAL STRUCTURES YOU NEED THE IMPRINT OF THESE MICROBES. THERE IS AN IMPORTANT ROLE IN FUNCTION AND EXTREMELY IMPORTANT OF THESE MICROBES IN CONTROLLING THE TISSUE FUNCTION AND ALLOWING CELLS TO EXERT EFFECTIVE FUNCTION AT THE SITE REQUIRED. AND THIS REALLY LINKED THE MICROBE TO A LOT OF BENEFICIAL OUTCOMES. THE MICROBE ARE EXTREMELY IMPORTANT FOR THE CONTROL OF INFECTION. THEY HAVE SHOWN TO BE IMPORTANT FOR THE CONTROL OF VACCINE, AND DEVELOPED ORALLY. SO HAS BEEN SHOWN TO REALLY BEAUTIFUL WORK DONE IN THE NIH TO THE IMPORTANT CONTEXT OF IMMUNOTHERAPY. SO THIS WAS LED BY THE GROUP OF [INDISCERNIBLE], BUT FOLLOWED BY MANY GROUPS INTERNATIONALLY, NOT ONLY LEVEL OF [INDISCERNIBLE] BUT IN THE CONTEXT OF CLINICAL STUDY. I REALLY HIGHLIGHTED THE IMPORTANCE OF THE GUT MICROBIOTA ALONG OFFICIAL RESPONSES TO CANCER TREATMENT. OF COURSE BECAUSE THE MICROBIOTA, THIS CAN HAVE NEGATIVE OUTCOMES FOR THE HUMAN SYSTEM. THEY HAVE BEEN LINKED TO DISORDERS, TO THIS MICROBE. THEY HAVE BEEN SHOWN TO BE IMPORTANT FOR METABOLISM SYNDROME. TYPE ONE AND TYPE II DIABETES. AND IMPORTANTLY, THE BIOSECURITY HAS BEEN LINKED TO THE DEVELOPMENT OF ALLERGY AND DISTURBED RELATIONSHIP WITH THE MICROBE EARLY IN LIFE HAS BEEN PROPOSED AS A CAUSATIVE AGENT OF LONG TERM ALLERGY RESPONSES. SO THE WORK THAT WE HAVE DONE OVER THE LAST YEARS ATTEMPTED TO EXPLORE THE CROSS TALK BETWEEN THE MICROBIOTA PATHOGENS. WE HAVE SHOWN AS WELL AS MANY OTHERS IN THE FIELD THAT THE MICROBIOTA WAS ABLE TO CONTROL EVERY STEP OF THE INTERACTION WITH THE PATHOGEN RANGING FROM TRANSMISSION TO RESOLUTION OF THE INFECTION AND TISSUE REPAIR. BUT BEFORE MOVING FORWARD I WANTED TO HIGHLIGHT AN IMPORTANT POINT THAT ALTHOUGH OFTEN WE SEPARATE MICROBE IN DISTINCTIVE PHASE, THE [INDISCERNIBLE] ARE MORE COMPLEX THAN THAT. THE LARGE NUMBER OF MICROBE THAT CAUSE DISEASE ARE NORMAL CONSTITUENTS OF THE MICROBIOTA THAT CAN BE PRESENT IN ALL OF US IN MANY CIRCUMSTANCES. SO WHAT THIS PATHOGEN CAN CAUSE A DISEASE IN THE CONTEXT OF IMMUNOSUPPRESSION, ANTIBODY TREATMENT, COINFECTION OR IN THE CONTEXT OF CERTAIN ENVIRONMENTAL TRIGGERS. UNMOST CIRCUMSTANCES THESE [NO AUDIO] GATEKEEPER OF THIS ENVIRONMENT THAT PREVENT EXUBERANT EXPRESSION OF THESE MICROBES. INDEED THE MIRES THAT LIVE WITH US OWE A PRIMARY SHIELD. IT’S PREVENTING PATHOGEN FROM INFECTING US. AND THEY DO THAT THROUGH MANY MECHANISMS. SOME OF THEM COULD BE INDIRECT. I’M GOING TO DISCUSS THAT FURTHER IN THIS LECTURE. BUT IT COULD ALSO BE DUE TO THE ACTIVITY OF IT MIRE, PRODUCT OF THE ACTIVITY OF THE MICROBIOTA. ALSO DUE TO DIRECT MECHANISM, MICROBE CAN TAKE A LOT OF SPACE AND ENERGY AND COMPETE AND PREHAVEN’T PATHOGEN. ALSO POSSESSING MOLECULES THAT CAN DIRECTLY INTERFERE WITH PATHOGEN OF OTHER MICROBES. THIS VARIES AND CAN PREVENT THE INFECTION WITH INEFFICIENCY AGENT. ONE SETTING IN WHICH THE PROTECTIVE EFFECT OF THE MICROBIOTA CAN BE REVEALED IN THE CONTEXT OF ANTIBODY TREATMENT. OAIN’T BIOTIC TREATMENT. IT CAN BE DEPLETED BY ANTIBIOTIC TREATMENT ALLOWING THE EMERGENCE OF MICROBES THAT CAN BE LIFE THREATENING. THIS REALLY LED TO A NEW APPROACH OF THERAPY FOR THESE MICROBES THAT HAS LED TO THE ASSOCIATION OF MICROBIOTA TRANSPLANT. THIS FORM OF APPROACH HAS PROVEN EXTREMELY EFFICIENT IN THE COUNTERREACTION OF CDIFFICILE. SO WHAT IS HAPPENING TODAY IN THE FIELD IS REALLY A LARGE AMOUNT OF RESEARCH, SOME OF IT LED BY RICK, TO UNCOVER THE APPROPRIATE CONSORTIUM OF MICROBE TO COMPETE WITH THOSE INEFFICIENCY AGENTS AND THIS LINE OF RESEARCH IS APPLIED NOT ONLY IN THE CONTEXT OF DEFENSES BUT ALSO IN THE CONTEXT OF IMMUNOTHERAPY. SO AS I MENTIONED BEFORE, ANOTHER EFFECT OF THE MICROBIOTA TO CONTROL PATHOGEN IS THROUGH THE CONTROL OF RESPONSES AND IMMUNITY. AND ONE OF THE REACTIONS IS TO AMPLIFY RESPONSES THAT ARE LINKED TO THE IL17 RESPONSES THAT ARE SO IMPORTANT FOR THE TISSUE RESPONSE TO PATHOGEN. SO QUITE A LONG TIME AGO NOW, TWO VERY TALENTED FELLOWS IN THE LABORATORY, JASON WAS A STUDENT AT THE TIME, AND [INDISCERNIBLE] IS IS THE WITH ME, THANK YOU, SHOWN A TREATMENT OF ANTIBIOTIC OF MICE CAN BE SUFFICIENT TO REDUCE THE ABILITY OF CELLS IN THE TISSUE TO PRODUCE CYTOKINE, AND IN PARTICULAR, IL17 OR INTERFERON GAMMA. SUCH EFFECT WAS LINKED TO CAPACITY OF THE HOST TO MOUNT PROTECTIVE RESPONSE TO THE PATHOGEN. SUBSEQUENTLY WORK DONE IN THE LABORATORY WAS ABLE TO SHOW IN THE GERM FREE MICE, ADDITION OF ONE SINGLE MICROBE WAS SUFFICIENT TO RESTORE 17 PRODUCTION BUT ALSO RESTORE PROTECTIVE RESPONSES LENGTHING THE MICROBIOTA TO PROTECTIVE EFFECT IN THE GI TRACT. THIS ACTUALLY LINE OF RESEARCH WAS EXTENDED IN THE FIELD IN MANY OTHER PATHOGENS, NOT ONLY THE ONE THAT LIVE IN THE GI TRACT, BY ALSO DISTAL, EXPERIMENTALLY, FOR EXAMPLE, RESPONSE TO FLU HAS BEEN SHOWN TO BE CONTROLLED BY THE MICROBIOTA AND MORE RECENTLY THIS HAS BEEN SHOWN TO BE TRUE IN THE CONTEXT OF MALARIA. BUT AS I MENTIONED BEFORE WE OFTEN REFER TO BACTERIA AS A MEMBER OF THE MICROBIOTA. WE SHOULD REMEMBER THIS MICROBE IS HIGHLY DIVERSE. IN THE CONTEXT OF COLLABORATIONS, LIBERTY AT MT. SINAI AND MIKE AT THE NIH WERE ABLE TO SHOW THAT [INDISCERNIBLE] PRESENT IN THE MICROBIOTA CAN PROMOTE MINTY TO PATHOGENS. YOU CAN SEE HERE SINGLE PRESENCE OF THESE ARE SUFFICIENT TO RESTORE IMMUNITY. THEN THEY SHOWED THE VIRUS CAN BE SUFFICIENT IN SOME CASES TO RESTORE PREDICTABILITY. BOTTOM LINE, DIFFERENT KIND OF MICROBE MAY ENGAGE IN IMMUNE RESPONSES, MAYBE IMPORTANT FOR THE HEALTH OF THE HUMAN SYSTEM, WHAT IS IMPORTANT TO REMEMBER AND THE [INDISCERNIBLE] THAT ALL MICROBES CAN PROMOTE THE IMMUNE SYSTEM AND COMPETE AGAINST PATHOGEN. HOWEVER, THE MICROBIOTA IS NOT ALWAYS THE PITCHER ELEMENT IN THE ENCOUNTER WITH PATHOGEN. THERE WAS BEAUTIFUL WORK DONE A FEW YEARS AGO HIGHLIGHTING THE IMPORTANCE. MICROBIOTA IN FAVORING TRANSMISSION OF PATHOGEN AND FAVORING PATHOLOGICAL CONSEQUENCE OF INFECTION. WORK DONE BY [INDISCERNIBLE] SHOWED THAT ABILITY OF AN EGG TO HATCH WAS DEPENDING ON THE SENSING OF FACTOR IN THE GI TRACT, IN PARTICULAR [INDISCERNIBLE] THAT ALLOWED THE WORM TO BECOME INFECTED. WORK SHOWS THAT VIRUSES ACQUIRED ORALLY HIGHLIGHTS THE IMPORTANCE OF THIS MICROBE IN SOME CASES TIN PROMOTION OF INFECTION. IMPORTANTLY WORK WE HAVE DONE AS WELL AS OTHERS [NO AUDI] I’LL DISCUSS THAT IN THE NEXT FEW SLIDES. WORK DONE A FEW YEARS AGO HIGHLIGHTED THE IMPORTANCE OF MOUNTING DISALLY FROM THE GI TRACT. ALTHOUGH THIS MICROBE CONTROLS THE SYSTEM THEY ARE NOT . THIS IS DUE TO THE FACT THAT THERE IS MUCUS LAYER. AND THIS REALLY PREVENTS EXUBERANT SENSING OF THE MICROBIOTA AND INFLAMMATORY. WHAT WE HAD SHOWN IS IN THE CONTEXT OF ACUTE INFECTION. THIS IS REMOVED AND NOW THE MICROBIOTA ARE IN TIGHT CONTACT, BECOME HIGHLY INFLAMMATORY. IN ADDITION, IN THIS CASE, WE CAN FIND MICROBES THAT ARE IN THE GI TRACT TRANSLOCATING AND PRESENT IN DISTAL TISSUE. THE CINNAMON HAS BEEN SHOWN BY THE BEAUTIFUL WORK OF [INDISCERNIBLE] IN THE CONTEXT OF BOTH HIV IN WHICH MICROBE TRANSLOCATION IS IMPORTANT FOR THE PATHOGEN OF THE INFECTION. RECENTLY OTHER WORK DONE IN OTHER ACUTE INFECTIOUS MODEL REVEALED IN LARGE MEMBERS OF INFECTIOUS SYSTEMS, IT CAN BE FOUND IN THE PERIPHERY. AND ADDITIONAL CONSEQUENCE OF THIS CHANGE OF THE RELATIONSHIP WITH THE MICROBIOTA IS THE FACT WE HAVE CHANGED THE QUALITY OF THE MICROBES PRESENT IN THE BI TRACT. BECAUSE OF THE INFLAMMATORY STATUS THIS LEADS TO THE ABERRANT OVEREXPRESSION OF CLASS OF MICROBE, FOR EXAMPLE, IN THE CONTEXT OF [INDISCERNIBLE], GAMMA BACTERIA, AND IN PARTICULAR [INDISCERNIBLE] WOMANS VERY DOMINANT, TAKING OVER THE ENTIRE GI TRACT. THESE ARE A CAUSATIVE AGENT OF THE PATHOLOGICAL RESPONSE OF THE PRIME MINISTER. IN MANY CIRCUMSTANCES, THE PATHOGEN IS NOT DUE TO THE PATHOGEN ITSELF BY DO TO AN ABERRANT RELATIONSHIP IN THE MICROBIOTA AND OVER-EXPRESSION THAT ARE HIGHLY INFLAMMATORY. SO THIS HAS CONSEQUENCES FOR THE ENVIRONMENT OF THE GI TRACT THAT REALLY EASE UNDER EXTREME PRESSURE. THE GI TRACT NEEDS TO MAIN TAKEN TOLERANCE TO IMPORTANT ANTIGENS BUT ALSO THE MICROBIOTA. AT THE SAME TIME DEALING WITH ACUTE INFECTION THAT CAN REPRESENT FREQUENT OCCURRENCE. FOR HUMAN HEALTH. SO OVER THE LAST FEW YEARS WORK THAT WAS DONE IN THE LABORATORY REVEALED IN THE CONTEXT OF AN INFECTION, YOU CAN TRANSIENTLY ALTER A RELATIONSHIP WITH THE BENEFICIAL AGENT. AND IN THE CONTEXT OF INFECTION, AN ANIMAL WILL DEVELOP FOOD ALLERGY IF THE FOOD IS INTRODUCED AT THE SAME TIME OF THE ACTIVE INFECTION. AT THE SAME TIME, WE HAD ACTUALLY SHOWN IN CERTAIN INSTANCES IN THE CONTEXT OF INFLAMMATORY, THE IMMUNE SYSTEM IS NO LONGER ABLE TO DISCRIMINATE BETWEEN THE PATHOGEN AND CAN DEVELOP AGGRESSIVE HUMAN RESPONSES, THINGS THAT HAVE LONG TERM CONSEQUENCES FOR THE GI TRACT. MORE RECENTLY, A TALENTED TEAM IN THE LABORATORY DECIDED TO EXPLORE THE POSSIBILITY THAT SOME INFECTION MAY PUSH THESE FORWARD AND MAY CREATE A POINT OF NO RETURN FOR THE IMMUNE SYSTEM. THE RELATIONSHIP WITH THE MICROBIOTA FOOD ANTIGEN. SO THE MODEL THEY DECIDED TO EXPLORE IS A MODEL OF ACUTE GI INFECTION DUE TO TUBERCULOSIS, A PRIME MINISTER OF HUMAN BUT ALSO INFECTS MICE. THIS CAN INDUCE ACUTE INFECTION. WHAT WE’RE ABLE TO SHOW IS DESPITE THE FACT THE MICROBE IS NOT PERSISTENT, IT WAS A SCAR IN THE TISSUE. IN PARTICULAR, THE LEVEL OF THE LYMPH NODE. AS YOU CAN SEE, THIS IS A MISENTRY LYMPH NODE THAT TRAINS THE GIT. THIS IS WHAT HAPPENED TO THE LIMP NOTICED AFTER INFECTION. THERE IS PROFOUND REMODELING. ALWAYS A FEAR. SO THERE IS A PROFOUND REMODELING OF THE [INDISCERNIBLE]. YOU CAN SEE THIS PASSIVE INFILTRATED NUT TRA FILLINGS AT THE CENTER. THIS IS NOT INEFFICIENCY PROCESS. THIS IS A SCAR POST INFECTION. SO WE BEGAN ACTUALLY TO EXPLORE THE QUALITY OF THESE LYMPH NODES AND ABLE TO SHOW IN A SURPRISING MANNER THAT THE ONE POPULATION OF CELLS WAS ABSENT FROM THE LYMPH NODES. YOU CAN SEE HERE THAT THIS POPULATION OF CELL THAT IS A DENDRITIC CELL THAT IS ABLE TO MIGRATE, IS COMPLETELY ABSENT MOST INFECTION, AND FOR THE ENTIRE LIFE OF THE ANIMAL. HE HAD PERMANENTLY REMOVE ONE POPULATION OF DENDRITIC CELLS. IN COLLABORATION WITH [INDISCERNIBLE], WE WERE ABLE TO SHOW USING A TECHNIQUE THAT, INDEED, THIS POPULATION OF DENIED DRAYEDIC CELLS WAS REMOVED, WHILE THE OTHER POPULATION WERE STILL THERE. WHEREVER IT WAS REALLY STRANGE, TIN TISSUE ITSELF, THE DENDRITIC CELLS WERE PRESENT. SO IN THE GI TRACT TO RESPOND TO ANTIGEN IN BOTH REGULATORY MANNER OR AGGRESSIVE, YOU NEED CERTAIN CLASS OF DENDRITIC CELLS, EXPRESSING THIS LINKED AWAY FROM THE ANIMAL TRAJECT RE. INSTEAD OF GOING TO THE LYMPH NODE, THEY WERE DEVIATED IN WHICH NOW THEY CAN ACCUMULATE. YOU CAN SEE THEY CAN FIND A LARGE NUMBER OF THOSE WITHIN THE ADIPOSE TISSUE ITSELF. THE CELLS HAVE [INDISCERNIBLE] FROM TRAJECTORY AND NOT ACCUMULATE IN THE TISSUE. SO HAVING AN INTERPRETATION OF THE DIALOGUE BETWEEN THE TISSUE AND LIMP NOTICED COULD HAVE CONSEQUENCES. THIS IS WHAT WE TESTED, LOOKING AT THE ABILITY OF THE ANIMALS POST INFECTION TO DEVELOP NORMAL RESPONSE TO GI TRACT. WE WERE ABLE TO SHOW THE ANIMALS ARE NO LONGER ABLE TO DEVELOP — IT CAN BE VISUALIZED BY THE ABILITY OF THE ANIMALS TO DEVELOP REGULATORY CELLS. WE HAVE EVIDENCE THEY DO BLOCK FOOD ALLERGY POST INFECTION. IMPORTANTLY, THE ANIMALS ARE ALSO NOT ABLE TO DEVELOP RESPONSE TO ORAL VACCINE, AND COMPLETELY ABOLITION THE ABILITY TO MOUNT ADAPTIVE RESPONSES TO EVACUATION AND IN PARTICULAR IL17. SO THE ABILITY OF THE GI TRACT TO MOUNT COHERENT RESPONSE TO ORAL ANTIGEN IS FOR THE LONG RUN. SO COMING BACK TO THE MONTREAL, GOING TO –S — IF YOU HE ELIMINATE, THIS, YOU ELIMINATE THE CONSEQUENCE OF THE INFECTION AND RESTORE THE ABILITY OF THE ANIMAL IN RESPONSES. SO THIS MODEL ACTUALLY ALLOWS US, THE EXPERIMENT ALLOWS US TO PROPOSE THE FOLLOWING MODEL THAT SOME INFECTION HAVE THE ACT TO CREATE A SCAR FOR THE IMMUNE SYSTEM. THEY CAN DO THAT BY CREATING DAMAGES. THIS NETWORK DAMAGE ALLOWS THE DIFFUSION BETWEEN THE ADIPOSE TISSUE, MAINETINEED CREATING AN INFLAMMATORY LOOP THAT DEFLATES CELLS AND SHUT DOWN ALL DIALOGUE BETWEEN THE TISSUE AND THE LYMPHOID STRUCTURES. THESE COULD HAVE LONG TERM CONSEQUENCES FOR THE HOST. WE COULD SPECULATE, IN SOME CASES THIS MAY LEAD TO ACTIVITY OF THE MICROBIOTA, PREDISPOSED TO [INDISCERNIBLE]. MAYBE ONE OF THE AGENTS, IMPORTANTLY, THIS MAY BE ONE OF THE EXPLANATIONS FOR THE FAILURE TO DEVELOP ORAL VACCINE IN PART OF THE WORLD IN WHICH THE INFECTIOUS BURDEN IS SO HIGH. ON THE OTHER HAND WE NEED TO REMEMBER IT’S EXTREMELY IMPORTANT FOR THE ABSORBS OF LIPID. ANIMALS DO GAIN MORE WEIGHT AND DEVELOPS AN ABBERERANT RELATIONSHIP. THESE PR PROPOSED A MOD 8, THE INEFFICIENCY IS NOT THE PROBLEM BUT THE TRACE OF THE COPQUENCE OF INFECTION, MAYBE UNDERLYING CAUSE FOR THE DEVELOPMENT OF COMPLEX DISEASE. MAY BE LOOKING BEYOND THE GENES TO THE EFFECT OF THOSE MICROBES, AND IN EARLY LIFE, IN THE INDUCTION OF INFECTIOUS DISEASE MAY BE IMPORTANT THINGS TO DO. SO I HAVE MENTIONED SOME WORK AT THE GI TRACT, WHERE MOST OF THE FIELD AND MOST OF OUR WORK IN THE PAST HAD BEEN FOCUSED ON. HOWEVER, A FEW YEARS AGO WE BECAME INTRIGUED THAT OTHER TISSUE OUTCOME COULD BE CONTROLLED. EVERY SURFACE IS COLONIZED BY MICROBES. THE SKIN IS VERY LARGE SURFACE, A TARGET OF MANY INFLAMMATORY DISORDERS. PORTAL OF ENTRANCE OF PATHOGENS AND THE SITE OF DEVELOPMENT OF MANY TUMORS. ALSO HOME TO A LARGE NUMBER OF MICROBES. THESE MICROBES ARE IN DEEP STRUCTURES, SWEAT GLANDS, AND FUDGE EYE, BACTERIA AND WHAT INSPIRES US TO GO THIS DIRECTION WAS A BEAUTIFUL WORK DONE BY [INDISCERNIBLE] AT THE NIH THAT REALLY UNCOVERED REMARKABLE PARTTITIONENING IN THE MICROBE PRESENT IN HUMAN SKIN. SURVEYING THE SKIN OF HEALTHY DONOR THEY WERE ABLE TO SHOW EACH COMPARTMENT WAS ITS OWN COMMUNITY OF MICROBE THAT WAS VERY MUCH DICTATED BY THE NUTRIENT PRESENT IN THE SITE. TRUE FOR NOT ONLY BACTERIA BUT FUGI. SIMILAR WORK AGAIN HIGHLIGHTED THE IMPORTANCE OF THIS IN THE CONTEXT OF INFLAMMATORY STATES OR DISEASE STATE SHOWING ASSOCIATION AND NOW HAVING PROVEN RECENTLY TO EXPERIMENTAL DATA, CLASS OF MICROBE CAN INFLUENCE INFLAMMATORY DISORDERS, SHOWING A CHANGE IN THESE MICROBIOTA IN THE CONTEXT OF PRIMARY IMMUNODEFICIENCY. THIS LINE OF RESEARCH HAS EXTENDED TO MANY DIFFERENT GROUPS, INTERNATIONALLY, HIGHLIGHTING ALMOST EVERY SKIN INFLAMMATORY DISORDER THERE IS DIFFERENT KIND OF MICROBE THAT LIVES AT THE SURFACE OF THE SKIN. TO MELANOMA. SO VERY BRAVE GRADUATE STUDENT JOINED ME LAB, WANTED TO SEE THE MICROBE LEAVING THE SKIN COULD BE IMPORTANT FOR THE IMMUNE SYSTEM. SHE LOOKED AT ANIMALS RAISED IN COMPLETE ABSENCE OF MICROBE, GERM FREE MICE. SHE WAS ABLE TO SHOW IN AN ANIMAL WITH NO BACTERIA, IN THE GI TRACT OR SKIN, THESE ANIMALS HAVE NO CAPACITY TO PRODUCE INFLAMMATORY CYTOKINE, IL17 AND INTERFERON GAMMA AT THE LEVEL OF THE SKIN. SHE WAS ABLE TO DO DIFFERENT EXPERIMENT TO PROVE THIS EFFECT WAS INDEPENDENT OF THE MICROBIOTA, AND IN THE SKIN, VERY IMPORTANT FOR THE LOCAL IMMUNITY. SHE WAS ANNUAL TO SHOW — ABLE TO SHOW IL1 ALPHA. SO I’M GOING TO GIVE YOU A COUPLE OF SLIDES FROM HER WORK TO MOVE ON TO MORE RECENT DATA. SHE WAS ABLE TO SHOW USING AN INFECTIOUS MODEL, IF YOU INFECT AN ANIMAL UNDER GERM FREE CONDITIONS, AN ANIMAL THAT HAS BACTERIA, AND UTILIZED DIFFERENT TREATMENT, ROLLIZATION OR NOT, ORAL ANTIBIOTICS SHE WAS ABLE TO SHOW IN A GERM-FREE MICE, THE LESION WAS WAY SMALLER THAN IN THE SPF MICE. WHEN THE MICE HAVE BACTERIA, THE LESION AND INFLAMMATION IS VERY HIGH. WHEN THE MICE ARE GERM FREE, THEY HAVE LESS INFLAMMATION COMING BACK TO THE POINT, INFLAMMATION IS ACTUALLY REDUCED. NOT HAVING INFLAMMATION IS NOT ALWAYS A PITCH THING FOR THE IMMUNE SYSTEM. THE ANIMAL IS NOT ABLE TO MOUNT ADAPTIVE RESPONSES PROPERLY. THIS IS IMMUNE RESPONSE AGAINST THE PARASITE THAT YOU HAVE IN AN SPF MICE, ACTUALLY [INDISCERNIBLE] INTO SKIN TO SEE WHAT THEY CAN PRODUCE THAT IS IMPORTANT FOR THE CONTROL OF THE INFECTION. THIS IS HAPPENED IN GERM FREE MICE, NOT ABLE TO DEVELOP ADAPTIVE RESPONSE TO PATHOGEN, AND INCAPABLE TO CONTROL THE INFECTION. HIGHLIGHTED THAT THE SKIN MICROBIOTA WAS FUNDAMENTAL IN CONTROLLING LOCAL IMMUNITY. SO MORE RECENTLY, WE MOVED IN A DIFFERENT STRATEGY, DIFFERENT APPROACH. THE REASON BEHIND IT WAS INSPIRED BY THE WORK OF JILLION HIDE A. WANTED TO WORK IN A MORE COMPLEX SYSTEM. USING ONE BACTERIA IN AN ANIMAL IS ABHERANT SETTING. WHAT I WANTED TO UNDERSTAND IS TO WHICH EXTENTED YOU CAN TAKE THE TWO MICROBE, APPLY TO AN ANIMAL JUST AT THE SURFACE OF THE SKIN AND SEE IF THESE COULD CHANGE THE IMMUNE SYSTEM. THIS HAS POTENTIAL APPLICATION IN THE CLINIC. THE SETTING IS SIMPLE. ANIMALS ARE NOT TOUCHED, NOT SHAVED. JUST APPLIED A DIFFERENT CLASS OF MICROBES. 2 WEEKS LATER THE IMPRINTING IS ASSESSED. FEW CONDITIONS WERE ESTABLISHED TO MAKE SURE WE COULD UTILIZE DIFFERENT [INDISCERNIBLE]. THEY COULD NOT CAUSE INFLAMMATION. THEY NEED TO ESTABLISHMENT PERSISTENT ASSOCIATION. AND IMPORTANTLY, THEY WERE NOT — BEFORE ASSOCIATION. SO REALLY, AN EXPERIMENT TO TRY TO SEE WHAT HAMID TO THE IMMUNE STEMMING. THE REAL LIFE EXPERIMENT, YOU ACQUIRING A DOG FOR EXAMPLE, WHAT DOES HAPPEN TO YOUR IMMUNE SYSTEM? THIS LED TO MANY PEOPLE GETTING ISOLATES FROM DIFFERENT SETICS RAINING FROM ANIMALS, ALSO IN THE CONTEXT OF PATIENTS. TRYING TO ASCRIBE DIFFERENT KIND OF MICROBE TO DIFFERENT SIGNATURE. THIS HAS BEEN QUITE SUCCESSFUL IN THE ALAB ALLOWING US TO UNCOVER SPECIFIC ASSOCIATION BETWEEN UNIQUE MICROBE AND DIFFERENT IMMUNE CELLS IN THE TISSUE. I’LL DISCUSS ONE OF THEM. SO A FEW YEARS AGO, ABLE TO SHOW THAT AN ANIMAL APPLIED WITH [INDISCERNIBLE], OF COURSE A COMMON SKIN [INDISCERNIBLE], CAN INDUCE VERY POWERFUL CD8 RESPONSE WITHIN THE SKIN ENVIRONMENT. THOSE ARE QUITE UNIQUE. THEY CAN PRODUCE IL17 OR INTERFERON GAMMA. THIS WAS QUITE INTRIGUING, A FACT OF THIS SPECIFIC BACTERIA, NOT OTHERS, AND MORE IMPORTANTLY [INDISCERNIBLE]. HIGHLIGHTING THE IMPORTANCE OF THINKING ABOUT DIFFERENT ISOLATE IN ASSOCIATION WITH THE IMMUNE SYSTEM. NOT JUST THE WHOLE SPECIES. THIS WAS NOT A BUY STANDARD RESPONSE. WORK DONE BY A LABORATORY UNCOVERED THE ANTIGEN SEEN BY THE IMMUNE SYSTEM, PROVED THIS WAS AN ANTIGEN SPECIFIC RESPONSE. I REMIND YOU, THIS IS NOT INVASIVE, JUST LOOKING AT THE SURFACE OF THE SKIN. THIS LED US TO BEGIN TO EXPLORE SOME OF THE MECHANISMS AND FEATURES OF THOSE RESPONSES. AND ONE THING THAT WAS QUITE INTRIGUING FOR ME WHEN WE STARTED THIS PROJECT, HAVING WORK ON HOST INTERACTION MY WHOLE LIFE, UNUSUAL, WAS THE ABILITY OF THE IMMUNE SYSTEM TO MOUNT IMMUNITY IN INFLAMMATION. SO ANY TIME WE WORK ON HOST INTERACTION WE FIND, THIS IS LEADING TO A AGREE OF INFLAMMATION. IN THIS CASE, THIS MICROBE THAT LIVED ON THE SURFACE OF THE SKIN, ADAPTIVE RESPONSES WITHOUT DISTURBING IN ANY WAY THE TISSUES. SO A UNIQUE FORM THAT REFERENDUM [INDISCERNIBLE]. SO THE FIRST THING WE DECIDED TO LOOK AT IS KIND OF CELLS THAT COULD BE IMPORTANT FOR THESE RESPONSES. AND WE FOUND THE ABILITY OF THIS MICROBE TO ENGAGE WAS LINKED TO THE ABILITY TO UTILIZE THE ANTIGEN NETWORK OF ANTIGEN PRESENTING CELLS. THE SKIN HAS ACTUALLY DIFFERENT PRESENTING CELLS THAT ARE PRESENT AT STEADY STATE. THE MICROBE [INDISCERNIBLE] WE BELIEVE THIS HELPED TO INDUCE RESPONSE IN A WAY THAT IS SO [INDISCERNIBLE] FOR THE TISSUE. IN PARTICULAR, CAPTURED BY CELLS THAT MIGRATE TO THE LYMPH NODE, BACK TO THE SKIN AND CAN ENCOUNTER CELLS THAT PRODUCE IL1, REALLY REQUIRED FOR THE LAUNCHING OF IL17 PREDICTION BY THESE CELLS. 2 STEP, VERY COORDINATED RESPONSES TO THIS. SO WHAT WE WANTED TO UNDERSTAND IS WHAT COULD BE THE POTENTIAL ADVANTAGE OF THESE RESPONSES FOR THE IMMUNE SYSTEM. ONE OBSERVATION THAT WAS HAD WAS THAT THESE CD8 CELLS HAD UNUSUAL [INDISCERNIBLE]. THEY WERE ABLE TO LOCALIZE, REALLY, THE OUTER LAYER F THE SKIN. THIS LED US TO HYPOTHESIS THAT MAYBE ONE OF THE FUNCTIONS OF THE CD8. THE CELLS MAY BE TO REINFORCE OTHER RESPONSES. BY DOING A SURVEY OF THE GENES EXPRESSED BY THOSE SITES WERE ABLE TO SHOW, UPREGULATED WHEN THE CD8 CELLS WERE PRESENT. SO WE TESTED THE POSSIBILITY OF HAVING THIS IMMUNITY AGAINST COULD HELP RESIST AGAINST OTHER INFECTION. FOR THAT, WE APPLIED THE ANIMAL WITH [INDISCERNIBLE] AND THEN CREATED AN INFECTION. USING AN ABRATION. AND COUPLE OF DAYS LATER WE LOOKED AT THE INNATE RESPONSE. WE LOOKED AT THE ABILITY OF THE HOST TO CONTROL THE INFECTION. CONTROL MICE CONTAIN CANDIDA ALBYCANS. ALLOWING THE ANIMAL TO BE BETTER PROTECTED. BUT RYE MOVING THE CD8 THAT WAS GENERATED PREVENTED THE INMATE RESPONSE AND WE BELIEVE LINKED TO THE ABILITY OF THE CD8 CELLS TO ENGAGE IN THE PEPTIDE PREDICTION. THE MODEL PROPOSED IS THAT IMMUNEY TO THE CLASS OF [INDISCERNIBLE] HAVE THE ABILITY TO GO [INDISCERNIBLE], THEY CAN REINFORCE THE PREDICTION. AND THESE CONTROL THE OTHER INFECTION, CREATING A BROAD INNATED RESPONSES IN THE TISSUE. CAN BE REFERRED AS [INDISCERNIBLE] AGAINST PATHOGEN. SO THE MICROBIOTA CAN CONTROL THE HUMAN SYSTEM MANY DIFFERENT MECHANISMS. ONE WILL BE, OF COURSE, A DIRECT MECHANISM BY DEFINING IL1 RESPONSES, A REMARKABLE ADJUVANT. IL1 ENHANCED IN THE TISSUE HAS THE ABILITY TO ACT DIRECTLY ON LYMPHOCYTES ALLOWING THE CELLS — FUNDAMENTAL FOR THE ABILITY OF THE CELLS TO PREDICTIVELY EFFECT IN THE TISSUE. BUT THESE RESPONSES ARE NOT JUST AT THE LEVEL OF THOSE RESPONSES CLEARLY, THERE IS INTERACT MECHANISM. THE MICROBIOTA CAN BE SENSED BY THE IMMUNE SYSTEM. I THINK THIS IS VERY FASCINATING OBSERVATION. SO IMPORTANT AND INDUCING IMMUNE RESPONSES. THERE IS WAY MORE COMMUNICATION AT THE LEVEL OF THE [INDISCERNIBLE] THAN THOUGHT. MICROBE CAN ENGAGE THE SYSTEM. ADAPTIVE RESPONSE AGAINST THEM. IN THE EPIDERMIS. THEY CAN PUT OUT PROTECTIVE RESPONSES. THEY HAVE FOUND THE CD8. THE CELLS INDUCED BY THE MICROBIOTA NOT ONLY ARE ABLE TO PROTECT AGAINST INFECTION, BUT ALSO ABLE TO INDUCE TISSUE REPAIR, SHOWING THIS IS A VERY DIFFERENT CLASS OF IMMUNITY HIGHLY ENTWINED WITH THE TISSUE NOT ONLY ABLE TO REFORCE [INDISCERNIBLE] BUT REINFORCES FUNDAMENTAL TISSUE OF TISSUE REPAIR. MUCH NEEDS TO BE LEARNED YET, AND MUCH MORE TO BE LEARNED ABOUT THE NATURE OF THE INTERACTION WITH THE MICROBES AND THE IMMUNE SYSTEM. SO IN CONCLUSION, THE MICROBES THAT LEAVE TO DIFFERENT DISTURB THINGS ENGAGE IN MANY MECHANISMS AND OTHER FACTORS FOR THE CONTROL OF INFECTION. THESE REALLY IS UNIQUE APPROACH FOUR THE FIELD TODAY. WHICH IS TO TRY TO EXPLORE MECHANIC STATISTICALLY HOW DIFFERENT CLASS OF MICROBES OR MOLECULES THAT ARE PRESENT IN PATIENTS CAN ACTUALLY ENGAGE SPECIFICALLY DIFFERENT CLASS OF IMMUNE RESPONSES. AND THESE CAN GIVE US A MECHANISTIC UNDERSTANDING OF THE [INDISCERNIBLE] IN WHICH MICROBE AND IMMUNE SYSTEM. BY LEARNING FROM THESE PATHWAYS AND THE MOLECULES AND FACTORS UTILIZED, WE MAY BE ABLE TO DEVISE A WHOLE NEW CLASS OF THERAPY THAT IS BASED ON THE UNDERSTANDING OF THIS INTERACTION. THIS THERAPY MAY HAVE ENORMOUS ADVANTAGE FOR A FIGHT AGAINST RESISTANT PATHOGEN, BUT IN THE CONTEXT OF DISEASE THAT ARE IN SUCH A NEED SUCH AS CANCER THERAPY. SO I HAVE TO THANK THE WONDERFUL PEOPLE THAT HAVE BEEN BRAVE ENOUGH TO JOIN MY LAB THE LAST FEW YEARS. AS I AMERICANS ADD FEW OF THEM, I NEED TO THANK EVERY SING HAVE OF THEM. ALL THE WORK DONE IS THEIR WORK. AND I REALLY THANK THEM FOR THE CREATEDIVITY AND MAKES MY LIFE A PLEASURE. THANK YOU TO ALL OF YOU, PAST AND PRESENT MEMBERS. IMPORTANTLY, I HAVE TO THANK ALL THESE FANTASTIC PEOPLE. TWO PEOPLE THAT ARE MORE THAN OTHERS, MY PARTNER IN CRIME, JULIE AND GORGEIO. REMARKABLE COLLABORATORS. I WOULD LIKE TO THANK ALL THE PEOPLE OVER THE FEW YEARS THAT HAVE HELPED BUILDING RESOURCES AROUND THE MICROBE RESEARCH, MANY PEOPLE THAT HAVE BEEN MENTORS AND HELPING US THROUGH THESE PROJECTS. THANK YOU VERY MUCH. [APPLAUSE]>>SO IT IS A GREAT PLEASURE TO PRESENT YOU WITH THE PLACK COMMEMORATING THIS OUTSTANDING LECTURE, AND TO CONGRATULATE YOU ON SUCH REALLY ELEGANT WORK.>>THANK YOU.>>THANK YOU VERY MUCH. [APPLAUSE] I ALSO BEFORE QUESTIONS, QUINN, REMIND YOU THAT AFTER WE HAVE A RECEPTION IN THE LIBRARY RIGHT NEXT DOOR. WE INVITE YOU ALL TO COME AND BOMBARD HER WITH QUESTIONS AND COMMENTS AT THAT TIME. BUT I THINK WE HAVE A FEW MINUTES NOW WITH MICROPHONES SO PLEASE FEEL FREE TO, IF YOU’RE WILLING, TO –>>YES.>>I’LL TAKE THAT.>>CONGRATULATIONS FOR EXPLORING THE BUGS IN OUR GUTS. SO I WAS WONDERING, WE KNOW ABOUT THE IMMUNE SYSTEM, THE GOOD EFFECTS OF THE BACTERIA, SO WHY DON’T WE USE THEM? IN TRANSLTIONAL RESEARCH? ARE YOU TOO SLOW? BECAUSE — [LAUGHTER]>>THAT’S EXACTLY WHAT IS HAPPENING. I THINK THERE IS REAL TRANSFORMATION RIGHT NOW. I WOULD DESCRIBE SOME HAPPENING IN THE CONTEXT OF TRANSPLANT FOR [INDISCERNIBLE] FOR EXAMPLE. OR DEVELOPMENT OF TARGETED STRATEGY TO UTILIZE CONSORTIUM BACTERIA. EXACTLY WHAT IS HAPPENING. THE POINTED I WOULD LIKE TO HIGHLIGHT, I THINK THERE IS STILL A LOT OF MECHANISTIC WORK THAT NEEDS TO BE DONE TO MAKE SURE THAT UTILIZE THE IMPORTANT MICROBES, SO I MAY BE TOO SLOW. THE FIELD IS MOVING FORWARD IN THIS DIRECTION.>>THE GUT MICROBE, EVERY TEAM WE HAVE INFECTION IN EVERY PARTS WE TAKE ANTIBIOTICS, SO IN KILLING ALL OF THAT, OBVIOUSLY, WE WANT TO KILL AND WE HAVE NO CHOICE, SO WHY DON’T WE TREAT SOME OF THEM AND FIND A GOOD WAY SO WE SAVE THEM IN THE FREEZER OR SOMEWHERE. ANTIBIOTICS, WE COULD USE IT TO REGENERATE THE WHOLE SYSTEM.>>YOU’RE CORRECT. WORK DONE RIGHT NOW AT SLOAN-KETTERING DOES EXACTLY THAT. TRANSPLANT, HAS BEEN SHOWN IN THESE PATIENTS. OF COURSE FROM DYSREGULATION OF THE MICROBIOTA BECAUSE OF THE TRANSPLANT BUT ALSO BECAUSE OF ANTIBIOTICS, THEY’RE STORING THE MICROBIOTA PRIOR TO TREATMENT. SO I THINK THIS IS PROBABLY GOING TO BE SOMETHING WAY MORE COMMON THAN WE THINK. WE CAN STORE AUGMICROBIOTA PRIOR TO TREATMENT OF ANY SORT. ANTIBIOTICS SAVE LIVES. BUT THEY CLEARLY HAVE CONSEQUENCES. THIS IS CLEARLY ONE OF THEM. SOME PEOPLE ARE MOVING FORWARD. MAY BECOME A PRACTICE VERY SOON IN MANY SETTINGS.>>SO IT’S COMING. THANK YOU.>>IT’S COMING.>>THE INITIAL COMMENTS YOU MADE ABOUT AVERAGE OF ABOUT 4GI INFECTIONS PER YEAR IN THE DEVELOPING AND REAL WORLD, YEARS AGO I SERVED IN MEXICO, AND I CAN TELL YOU FROM EXPERIENCE, I DIDN’T FIND THAT THERE WERE THROUGH MANY. MOST OF THE PEOPLE THERE HAVE EXPERIENCE IN IMMUNOLOGY IN TERMS OF THEIR — MOST OF THE PEOPLE DIE OFF IN THEIR INFANCY OF GI SYMPTOMS. I REMEMBER IN A PAEDIATRIC — IN MY INTERNSHIP, WE HAD A HUGE WOE COOLED THEM [INDISCERNIBLE]. IT WAS LIKE HUNDREDS, IF NOT — MAYBE NOT HUNDREDS. MAYBE 150 OR 200 CRIBS, THEY ALL HAD THE SAME THING. DIARRHEA. THY DRANK CONTAMINATED WATER. I DIDN’T SEE THEM HAULED OUT IN CASKETS, I’M ASSUMING THOSE ARE THE ONES THAT DIED OFF. THUS WHEN YOU GET INTO A GENERAL CLINICAL SITUATION, I DIDN’T FIND A LOT OF ADULTS COMING TO ME WITH A [INDISCERNIBLE] IN THE MEXICAN POPULATION. HOWEVER, I CAN SAY THAT THOSE THAT DID GET INFECTIONS WENT ON TO GET LIVER [INDISCERNIBLE], MIXED LIVER ABSCESSES WAS VERY COMMON IN INTERNAL MEDICINE. GI INFECTIONS PER SE, OTHER THAN [INDISCERNIBLE] IN VERY PAEDIATRIC, THEY WOULD HAVE WHAT’S CALLED [INDISCERNIBLE]. THEY GRIND THEIR TEETH AND THE MOTHER WOULD PULL OUT PART OF A WORM OR SOMETHING. OR FIND IT IN THE STOOL. THAT WOULD BE COMMON. THE IDEA THAT THERE IS 4 INFECTIONS PER YEAR IN AN ADULT POPULATION –>>NO. THIS WAS IN YOUNG CHILDREN.>>WHAT?>>IN YOUNG CHILDREN. THE DATA, INITIALLY WE GOT DATA IN THE CONTEXT OF LOW INCOME COUNTRY, CAME FROM BANGLADESH, AND REALLY TRACKED CHILDREN OVER TIME. SO MAYBE MEXICO WAS DIFFERENT. IN BANGLADESH THERE WAS A VERY HIGH BURDEN. IN TERMS OF NUMBER OF GI INFECTIONS, DO WE REPORT EVERY SINGLE INFECTION? I HAD TWO CHILDREN. THEY HAD A LOT OF INFECTIONS. SO I THINK WE ARE UNDER-REPRESENTING. THEY’RE NOT LIFE THREATENING. STILL MEANS THAT THE IMMUNE SYSTEM CAN BE CHALLENGINGED BY THE ENVIRONMENT. ONE THING REALLY IMPORTANT TO THINK IS WE PROBABLY NEED TO TRACK BETTER THE ENCOUNTER OF PEOPLE WITH INFECTION OVER TIME TO SEE WHICH ONE HAS ANTIBIOTIC OR NOT. YOU’RE CORRECT. PROBABLY MEXICO WAS LESS. IN BANGLADESH, THEY HAD A HYBRID OF INFECTION. I THINK THEY IDENTIFIED BECAUSE THEY HAD GOOD MEDICAL CARE.>>THANK YOU.>>GREAT TALK. IN THE BACTERIA THAT CAUSED THE SCARRING, IS THERE ANY — DO YOU HAVE ANY INDICATION THERE MAY BE SOMETHING THAT CAN REVERSE THAT? THAT CAN CAUSE THOSE DENDRITIC CELLS TO REMIGRATE? ANOTHER INFECTION, OR.>>SO REALLY, ANTIBIOTIC TREATMENTS — EVERYTHING COME BACK TO STEADY STATE AND REMOVE THE PRESSURE OF THE MICROBIOTA, YOU CAN RESTORE THE IMMUNE SYSTEM FUNCTION. WE CAN’T REPAIR BUT WE CAN REPAIR BY LIMITING THE INFLAMMATION THAT IS IMPORTANT FOR THE MIGRATION.>>THANKS.>>OKAY. ALL RIGHT.>>THANK YOU. [APPLAUSE] [APPLAUSE] 0

Leave a Reply

Your email address will not be published. Required fields are marked *