gut microbiota for health summit 2013 report

7/28/2019 Gut Microbiota for Health Summit 2013 Report

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S mm i r p24 -26 February 201 3

M a d r i d , S p a i n

2nd W or ld Summi t "Gut Mic ro b io ta fo r Hea l th"

L ki g c s l ch i sGut microbiota abnormalities involved in functionalbowel disorders

The precise genesis of the various functional bowel disorders (FBD) is still to beunravelled. Looking into the relations between gut microbiota and host hasopened a research avenue that will very likely lead to results that offer interestinganswers with a remarkable potential for clinical applications.

From le to right: moderator Dr Mark Porter (UK) in discussion with Prof. Fernando Azpiroz (Spain),Prof. Magnus Simrn (Sweden) and Prof. Giovanni Barbara (Italy)

FBD, such as irritable bowel syndrome(IBS) or dyspepsia, form a consider-able burden for the individual qualityof life, as well as for the public health sys-tems. FBD have a global prevalence of 11.2per cent, with a wide regional range from1.1 to 45 per cent, as Professor GiovanniBarbara (University of Bologna, Italy)pointed out. In countries such as Germany,Portugal and Switzerland, the annual costsper patient range between 700 and1,600.According to Prof. Barbara, there is increas-ing evidence that the gut microbiota is in-volved in the onset of FBD. He namedseveral bidirectional mechanisms betweenthe host and the intestinal microbiota, bywhich the latter can modulate gut motorfunctions. These mechanisms are related,

for example, to the release of neurotrans-

mitters or proteases, to the activation of toll-like receptors and to the production of short chain fatty acids (SCFA).

Every second patient consulting a gas-troenterologist complains of symptomstypical of FBD, said Professor FernandoAzpiroz (University of Barcelona, Spain),Chair of the Gut Microbiota & Health Sec-tion of the ESNM (European Society of Neurogastroenterology and Motility). Heconrmed the strong possibility of the gutmicrobiota to play an important role inFBD. He pointed to animal trials whichdemonstrate that the sensory pathwaysbetween gut and brain are affected by themicrobial composition, as germ-free ratsexhibit visceral hypersensitivity. Not onlythe absence of the gut microbiota, but also

its abnormal composition might induce

FBD. However, it is still unclear what suchresults, encouraging as they are, imply forthe clinical practice. To ll these gaps, Prof.Azpiroz asked for thorough physiologicaltests in order to better dene the varioussubgroups of FBD and then assign them todifferent microbial compositions.

SoMe ProbIotICS Can aLLevIate IbSOne microbiota-related factor that has fre-quently been held responsible for certainFBD, such as IBS, is small intestinal bacte-rial overgrowth (SIBO). But as ProfessorMagnus Simrn (University of Gothenburg,Sweden) pointed out, it is still unclear towhich extent SIBO is really involved in thepathogenesis, as the methodological va-lidity of the breath tests that have beenused to establish its causal role is ques-tionable. As regards possible treatments,Prof. Simrn presented studies which showthat some probiotics can alleviate IBSsymptoms, particularly gas-related ones,such as bloating. While meta-analysesconrm the benecial potential of probi-

otics, the evidence for the effects of par-ticular strains is limited. This calls, as Prof.Simrn said, for more in-depth trials con-cerning mechanisms explaining probioticefficacy in IBS.

ContentL di g xp s i M d id .......... 22nd Gut Microbiota for Health World Summitanother success & New AGA research centerC i g c s ......................... 3Stool transplants are highly effectivefor treating GI conditions

W p s g i s GI dis s s ...... 4Evidence for medical efficacyof pre- and probioticsP i ics d i c i i i s .... 5The underlying reality of gut feelingsD c i g s si .......... 6Microbiota and gut barrier leaksinvolved in disease onset

H w g i h l c ? ........ 7Diversity loss in the microbiota iso en associated with IBDP c ssi g h g ic p l .... 8Powerful techniques decipher theguts metagenome


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most popular topic, as the correspondingworkshop attracted the largest audiencewith over 100 participants. The summits attendees particularly welcomed thatample time for discussion had been allocated, so that a lively exchange of information, opinions and experiencesaccompanied the event from the start.

The summits digital communicationmeans were widely used, which demon-strated the ever- rising interest that gutmicrobiota research is provoking insidethe scientic community. More than

Wider attendance at 2nd GutMicrobiota for Health WorldSummit

270 researchers and clinicians from 25nations attended the conference, whichwas hosted by the Gut Microbiota & HealthSection of the ESNM (European Societyof Neurogastroenterology and Motility) a member of UEG (United European Gastro-enterology) and the AGA (AmericanGastroenterological Associa tion). Over thecourse of three days, the speakers offeredcutting-edge science, presented as a well-balanced mixture of lectures, workshopsand posters.

Poster exhibition at the 2nd World Summit Gut Microbiota for Health

300 tweets communicated event-relatedmessages via the summits twitteraccount (@GMFHx). Almost 50 new followers joined during the event. Morethan 180 experts from all over the worldfollowed the live coverage of the plenarysessions on the Experts Exchange websitegutmicrobiotaforhealth.com (available

here ). Not to forget an online press conference with journalists from all overthe world, which can be viewed here .

The 3rd Gut Microbiota for HealthWorld Summit will be held on8 and 9 March 2014 in Miami, USA.

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The summits topics, all related tothe gut microbiota, ranged fromvarious GI diseases to effects of pre- and probiotics, from the intestinalmicrobiotas interplay with brain functions to molecular biology researchmethods. The programme covered basicscientic and translational aspects of the

eld. The six workshops, which providedcontinuing education presented byworld-leading experts, were very well attended. Summaries can be found here .Pre- and probiotics turned out to be the

n w aGa s ch cA virtual home for scientic exchange and education

The American Gastroenterological Association (AGA), co-organiser of the 2ndGut Microbiota for Health World Summit in Madrid, recently founded the AGA Center for Gut Microbiome Research and Education. Its mission is to advance

research and education on the gut microbiome in human health and disease. Thefoundation of the center, which will serve as a virtual home for research activitiesand exchange, is based on the AGA Governing Boards conviction that the gut microbiome is among the most exciting and promising areas of science today andshould be a top priority for gastroenterology and the organisation as a whole. Thisis an incredibly exciting time in science, where technological advances provide anunprecedented opportunity to explore not only the composition, but also the func-tion of the microbial communities that live in our intestinal tract, said Prof. Wu,chair of the centers scientic advisory board, comprising distinguished experts inall subspecialties of the eld. It is hoped that the know ledge gained will providenew insights into disease pathogenesis and innovative therapeutic modalities.

To me, personally, to meet the world leaders, who have published extensively on the eld of the gut microbiota, all at on e meeting is a bon us .

L di g xp s i M d id
http://www.gutmicrobiotaforhealth.com/t/sessions-of-the-gmfh-2013-107http://www.gutmicrobiotaforhealth.com/t/online-press-conference-at-the-2nd-world-summit-gut-microbiota-for-health-98http://www.gutmicrobiotaforhealth.com/t/online-press-conference-at-the-2nd-world-summit-gut-microbiota-for-health-98http://www.gutmicrobiotaforhealth.com/t/online-press-conference-at-the-2nd-world-summit-gut-microbiota-for-health-98http://www.gutmicrobiotaforhealth.com/t/workshops-at-the-gmfh-2013-108http://www.gutmicrobiotaforhealth.com/t/workshops-at-the-gmfh-2013-108http://www.gutmicrobiotaforhealth.com/t/workshops-at-the-gmfh-2013-108http://www.gutmicrobiotaforhealth.com/t/sessions-of-the-gmfh-2013-107http://www.gutmicrobiotaforhealth.com/t/online-press-conference-at-the-2nd-world-summit-gut-microbiota-for-health-98http://www.gutmicrobiotaforhealth.com/t/workshops-at-the-gmfh-2013-108


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Infusion of diluted donor faeces through the colon

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The basic principle of FMT is the in-

fusion of diluted donor faecesthrough the colon or the nasoduo-denal route in order to restore the lack of diversity of the gut microbiota, which isassumed to play a major role in the onsetof many GI diseases. Dr Anne Vrieze

C i g c sStool transplants are highly effective for treating GI conditions

Faecal microbiota transplantation (FMT) is a rapidly acting treatment for recurrentC. difficile infection (RCDI). It also offers a promising outlook regarding other GIdiseases. While a large part of the knowledge about FMT so far has been gainedthrough practical experience, the systematic exploration of its potential is nowunder way.

(Academic Medical Center, Amsterdam,

The Netherlands) and Professor LawrenceBrandt (Monteore Medical Center, NewYork, USA) presented the audience withresults of clinical trials, as well as withcase studies and reports based on theirown clinical experience that impressively

demonstrated the potential of this treat-ment. As RCDI is a major eld of applica-tion, Dr Vrieze presented a study on theeffect of donor faeces in patients withthis condition, the conventional treat-ment of which with antibiotics o en fails.

Dr Vrieze described the safety proce-

dures, which make sure that the potentialdonors microbiota is healthy andmatches the recipients therapeuticneeds. She reported that 94 per cent of the patients who had received donor fae-ces were cured, compared to much lower

cure rates in the control groups who hadreceived conventional antibiotic treat-ment.

treatMent WItH ProMISInG futureThe high benefit of this comparativelylow-cost therapy was confirmed byProf. Brandt one of the FMT pioneers who provided an overview of the development of FMT during the lastdecades, as well as a follow-up study on

the long-term effects of the treatment,

both of which showed success rates of well over 90 per cent. Apart from RCDI,cases in which FMT has been shown tobe helpful include IBD, IBS and meta-bolic syndrome. Concerning the latter,Dr Vrieze presented a study thatshowed how faecal transplants of leandonors improved the insulin sensitivityof obese patients, as well as their gutmicrobial diversity. As Prof. Brandtpointed out, even in a number of non-GI-related diseases, such as Parkinsons,chronic fatigue syndrome and autism,FMT has been helpful.

However, as both experts made clear,there is still a whole range of questionswaiting to be answered. These concernpractical aspects (such as the rightamount of stool), the causative role of thegut microbiota in the different diseases,the need to further establish the efficacyof FMT, and the development of noveltreatments that could replace FMT in thelong run. One way might be the culturingof benecial microorganisms that could

be used for novel probiotics.

I was particularly intere st ed in the faecal microb iot a transplant discus si ons. I think this has a ver y i nteresting future. Th e microbiota in genera l i s the future inund er standing many of the di seases.

PRof.LAwRence

BRAnDt,Monteore

Medical Center,New York,

USA

DR Anne VRieze,

Academic Medical Center,

Amsterdam,The Netherlands


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Prebiotics are food for benecialintestinal bacteria! This catchydenition, presented by Dr KarenScott (University of Aberdeen, UK),stressed the clinical importance of prebi-otics, such as resistant starch andoligosaccharides. In her talk, Dr Scott out-lined the role of these prebiotics which occur, for example, in chicory asingredients that are fermented by gutbacteria, thus changing the compositionor activity of the microbiota in a positiveway. The main underlying process con-sists of the fermentation that results indifferent types of benecial SCFA. Thesecan help to protect the host against

bowel cancer, IBD, diarrhoea and consti-pation, or to moderate the course of dis-ease. Other positive effects are thedecrease of cholesterol and the increaseof calcium absorption.

SuffICIent evIDenCeThe clinical potential of some probioticswas at the centre of Professor Colin Hillstalk (University College Cork, Ireland). Hepointed out that between 2000 and2011, more than 1,000 publications on

human clinical trials with different probi-

W p s g i s GI dis s sEvidence for medical efficacy of pre- and probiotics

otics had appeared. The most commonlytargeted conditions for probiotics are IBS,diarrhoea, pouchitis, necrotising entero-

colitis and ulcerative colitis. Although notall of these studies have passed uncriti-cised, there is sufficient evidence, ac-cording to Prof. Hill, for the health benet

of some probiotics. What remains to beclaried is, among other things, whichtherapeutic outcomes are to be assignedto which bacterial strains. Prof. Hill pre-dicted a promising future: Probioticshave the potential to offer the cliniciananother weapon against GI conditions.

While research on probiotics has so far

mostly focused on the large intestine,

Professor Michiel Kleerebezem (Wagenin-gen University, The Netherlands) presentedndings that concern the interaction of

probiotics with the microbiota of the smallintestine, which forms the part of the gutwhere the initial interactions between foodand microbes occur and which is a highlyimportant region for controlling metabolicand immune functions. Prof. Kleerebezemdemonstrated that some probiotics exert

signicant inuence over genes involved inregulating the metabolism of cells lining thesmall intestine. Some of the observed ef-fects may be clinically signicant and maylead to the use of specic probiotic strains

for treatment.

Prebiotics can be found, for example, in chicory, probiotics in fermented dairy products

Over the past years, an ever-growingnumber of studies on the clinicalrelevance of pre- and probiotics havebeen performed. Although severalaspects still require clarication, a largebody of evidence in favour of theirbenecial impact has already beengathered.

F

O O D - m

i c r o -

f o t o l i a

C

h r i s t i a n J u n g -

f o t o l i a

PRof.coLin hiLL,

University College Cork,

Ireland

PRof.KARen Scott,

University of Aberdeen,

UK

PRof.MichieL

KLeeReBezeM,Wageningen

University,The Netherlands


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GI disorders are o en accompanied

by psychological symptoms, suchas anxiety or depression. This isdue to the tight interplay between thenervous system, the gut and theintestinal microbiota. Communication be-tween these three players runs bottom-up as well as top-down through a diversenetwork of signalling pathways, amongwhich the vagus nerve and the spinalchord are two important roads. ProfessorPremysl Bercik (McMaster University,Hamilton, Canada) presented a largenumber of mice trials that demonstratedhow closely emotional states depend on

P i ics d i c i i i sThe underlying reality of gut feelings

A widely ramied network of signalling paths enables a smooth and efficientcommunication between brain, gut and intestinal microbiota. Disturbance of this exchange,however, can severely affect the psychological balance. A growing number of ndingselucidate how strong the interdependence between these areas is.

the communication between the intes-

tine and the nervous system. Animalswith different kinds of GI infectionshowed anxiety- or depression-relatedbehaviour, accompanied by correspon-ding changes in neuroregulatory and

immunomodulatory processes. Also,Prof. Bercik could show how an induceddisturbance of the microbial composi-tion, o en combined with inammation,goes hand in hand with depression- oranxiety-related behaviour. On the otherhand, probiotics such as B. longum,

L. farciminis and L. rhamnosus can exert

a benecial effect, mediated through thegut microbiota, by reducing specic neuronal activities and thus inducing anormalisation of behaviour.

StuDy In HuManS ConfIrMS HyPotH-

eSIS GenerateD In anIMaL MoDeLSBy contrast with the abundance of animaldata, comparably few controlled studyresults have so far been provided on theconnections between gut, microbiota andpsychological conditions in humans. Thislends particular signicance to an inves-tigation that Professor Emeran Mayer(University of California, Los Angeles,USA) reported on: his team demonstratedthat some probiotics affect evoked brainresponses, in a measurable way, through

change of the gut microbial composition.The trial group consisted of 45 womenwho underwent an emotional reactivitytask that included viewing faces express-ing negative emotions, thereby activatingtask-related brain circuits concerned withthe central processing of afferent signalsfrom the gut. Brain imaging showed thatin those participants who had consumed a fermented milk product with probiotics,the neuronal response to the task was re-duced, compared to two control groupswithout intake of pro biotics. While Prof.Mayer cautioned against premature ex-trapolations from the study to complexhuman emotions, such as anxiety, he em-phasised the importance of having beenable to observe effects of some probi-

otics on the human brain.

There is a tight interplay between the brain, the gut and the intestinal microbiota

The gut microbiota plays important roles in meta - bolism, in the regulation of

the immune system, and not only in the functionof the brain, but actual ly inthe development o f the brainin the rst year s o f life.

C

L I P A R E A

. c o m

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d

i m d i m i c h -

f o t o l i a

PRof.eMeRAn MAyeR,

University of Califonia,

Los Angeles,USA

PRof.PReMySL

BeRciK,McMaster

University,Hamilton,

Canada


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How does the gut microbiota com-position inuence the develop-ment of obesity-related diseases?Professor Gary Wu (University of Pennsyl-vania, Philadelphia, USA) and his teaminvestigated the gut microbiota compo-sition and its correlation with food intakein 98 individuals, associating diet inven-tories with the outcome of the analysis of faecal samples. As a result, the individu-

als could be clustered into enterotypegroups, distinguished primarily by levelsof Bacteroides and Prevotella . Individualswho, over a long period of time, con-sumed more animal fat and less carbohy-drates showed a dominating amount of Bacteroides , while a high level of Pre-

votella indicated the reverse. This coin-

Microbiota composition andgut barrier leaks involvedin disease onset

The gut microbial composition respondsquickly to change of food, but onlylong-term diet can alter the enterotypestate. Another important mechanismunderlying obesity and metabolicsyndrome is the strong interplay of the gut microbiota, the bodys owncannabinoid system and leaks in thegut barrier.

cides with the nding that Prevotelladominates in agrarian societies, whileBacteroides are associated with a West-ern diet. Based on another trial, Prof. Wuand his team could also demonstrate that

the gut microbiobal composition alreadychanged measurably within 24 hours of initiating a high-fat/low-bre or a low-fat/high-bre diet. However, the alter-ations during the ten-day study were toosmall to affect the enterotype identity.This suggests that a long-term diet is nec-essary to induce alternative enterotypestates.

PrebIotICS benefICIaL In MetaboLICSynDroMeTo unveil the metabolic syndromes un-derlying physiological mechanisms is thegoal of investigations performed byProfessor Patrice D. Cani (University of Louvain, Belgium) and his team. Their re-cent ndings indicate that mutual inter-

actions between the gut microbiota, the

A low-fat/high-bre diet already changes the gut microbial composition within 24 hours

endocannabinoid (eCB) system and leaksin the gut barrier play an importantcausal role. The researchers found outthat, in obese patients, the gut barrier isleaky as its otherwise very tight junctionsare weakened. Hence, toxic molecules,so-called lipopolysaccharides (LPS) canpermeate this wall and provoke inam-matory reactions of immune cells. Thisfurther weakens the tight junctions, con-sequently raising the LPS level and thus

initiating a vicious circle. LPS are also as-sociated with the onset of insulin resist-ance and type 2 diabetes. An importantintermediary within this process is the in-tercellular network of the eCB system,

which, among other things, is involved inappetite control. Based on several trials,Prof. Cani showed that the gut microbiotacontrols obesity symptoms via modulat-ing the eCB system. Reversely, feedingprebiotics alters the microbial composi-tion in a way that downregulates the eCB

activity and reduces the symptoms.

C

e l s o P u p o -

f o t o l i a

I was particularly intere st ed in the implications o f diet and metabolic syndr ome, and

how the gut m i crobiota might modulate an d inuence the me ta bolic syndrome.

D c i g s si

PRof.PAtRice D.

cAni,University of

Louvain,Belgium

PRof.GARy

wu,University of

Pennsylvania,Philadelphia,

USA


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Diversity loss in the gut microbiota is o en associatedwith IBD

From antibiotics to faecal trans-plantation there is a broad rangeof IBD treatment options that arebased on altering the microbialcomposition. Improving their outcomeand determining the most suitableapproaches requires further researchon the gut microbiotas role indisease onset.

H w g i h l c ?

certain IBD patients might recruit a differ-ent microbiota from birth onwards.Environmental factors are not to be dis-regarded: for instance, repeated anti -

biotic treatments during adolescenceappear to increase the risk to developCrohns disease by leaving an inerasablengerprint in the gut microbiota. Nutri-tion also plays an important role, though,according to Prof. Haller, it still has to beexamined how diet and gut microbiotainteract precisely with regard to theonset and course of IBD.

CuStoMISeD treatMentS DeSIreDAdditional clinical evidence for the gutmicrobiotas key role in IBD was providedby Professor Balfour Sartor (University of North Carolina, Chapel Hill, USA). Hepointed to several studies showing thatnumerous Crohns disease and ulcerativecolitis patients have an imbalanced mi-

crobiota with an increase of detrimental

and a decrease of protective strains. Theexact proportions of this imbalance, how-ever, differ between individuals, whichcorresponds to the fact that, on the otherhand, what constitutes a healthy micro-bial balance is also unique in each indi-vidual. Prof. Sartor named several ways of repairing a disturbed microbiota com-position, among them the intake of com-mensal bacteria, which, according to him,

are more likely to have lasting therapeu-tic effects than traditional probioticstrains. As regards faecal microbiotatransplantation, Prof. Sartor acknowl-edged its success in patients with recur-rent C. difficile infection, while taking a

more sceptical stance towards its poten-tial for IBD, as there is a lack of trial re-sults. In any case, every treatment shouldbe guided by the insight that everyonesmicrobiota is different, thus requiring acustomised instead of a uniform ap-

proach, said Prof. Sartor.

What constitutes a healthy microbial balance is unique in each individual

What exactly is a normal gutmicrobiota composition? Thishas not been dened yet, saidProfessor Dirk Haller (Technical Univer-sity of Munich, Germany), pointing outthat, at the same time, it is an establishedfact that many inammatory bowel dis-eases are accompanied by a signicantloss of bacterial diversity. The extent of this decrease can depend on the disease

location: according to Prof. Haller, ilealCrohns disease is connected with aheavier loss of bacterial richness thancolonic Crohns disease, although theamount of bacteria in the colon is larger.Another factor most likely to be involvedin the intestinal microbial composition isgenetic predisposition, which means that

From this summit,I gained the insight that investigating the gut microbiota is muchtrickier than I had assumed.

PRof.DiRK hALLeR,

TechnicalUniversity of

Munich,Germany

PRof.BALfouR SARtoR,

University of North

Carolina,USA

k

a s i a s t o c k -

f o t o l i a


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P c ssi g h g ic p lPowerful techniques decipher the guts metagenome

The gut microbiota includes far more genes than the human genome itself.Comprehensive analysis of this astounding diversity is crucial to improve thetreatment of many GI diseases. Precise and efficient methods suitable foranalysing and processing vast amounts of data are a prerequisite.

human gut microbiota harbours four majorphyla: Bacteroidetes, Firmicutes, Actinobac- teria and Proteobacteria . The main metage-nomic questions to be answered areprecisely which kinds of microbes exist inthe gut and what functions they have. Atechnique particularly suited to answer therst question is the microbiota 16S geneproling (also called 16S barcode proling),which is based on the analysis of the 16SrRNA gene, a fundamental molecule of the

bacterial machinery. The procedure consists

of studying phylogenetic markers using 16rRNA gene amplication by pyrosequencing.

InveStIGatInG by SHotGunSequenCInGA second, particularly fast method is

shotgun sequencing, which is frequentlyused to analyse the whole of the micro-biota in order to establish the functionalrepertoire and the abundance of micro-bial genes. This approach is based onanalysing short and randomly fragmen-tised DNA strands. Bioinformatics helpsto put the resulting pieces together untilthe genetic picture is complete. The

application of these methods in the eldof gut microbiota research has led,among other things, to the detection of

three gut enterotypes bacterial communities, into which humans can besubclassied, as Professor StanislavDusko Ehrlich (INRA, Jouy-en-Josas,France) indicated. In his opinion, the enterotypes will be key in linking dis-eases with certain microbial communi-ties. A reference catalogue of theintestinal microbial genes, in which theresults of microbial DNA analyses of individuals are mapped, is a crucial element to obtain individual microbiotaproles. Studies that compared obese tolean individuals and IBD patients tohealthy controls demonstrated consider-able differences in the microbiota composition and diversity. According toProf. Ehrlich, this opens up promisingpaths to better understand the involve-ment of the microbiota in a broad rangeof clinical issues.

DNA analysing techniques are crucial for further progress in gut microbiota research

Published in June 2013 by:ESNMs Gut Microbiota & Health Section AGAConcept & Execution:impressum health & science communicationLayout: KaroGrak

As Professor Paul OToole (University College Cork, Ireland) and ProfessorJol Dor (INRA, Jouy-en-Josas,France) explained, the key to exploring thegut microbiota genes is metagenomics, aterm denoting the investigation of thegenes of all bacteria, viruses and fungi thatform the intestinal microbiota. Bacteria,which are currently at the centre of gutmicrobiota research, can be classied, indescending order, by phylum, class, order,family, genus, species and strain. The

PRof.JoL DoR,

INRA,Jouy-en-Josas,

France

PRof.S. DuSKo

ehRLich,INRA,

Jouy-en-Josas,France

PRof.PAuL

otooLe,University

College Cork,Ireland

S

e r g e y N i v e n s -

f o t o l i a

gut microbiota for health summit 2013 report

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