gmfh summit report new

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S r26-28 March 2012

v i a n , F r a n c e

1 s t W o r l d S u m m i t " G u t M i c r o b i o t a f o r H e a l t h "

For three days the charming town ofvian, located at Lake Geneva, pro-vided the venue for a conference

on the latest developments in the fieldof gut microbiota research. Round tables,lectures and workshops organised by theGut Microbiota & Health Section of theEuropean Society of Neurogastroenterol-ogy and Motility (ESNM) and held byinternationally distinguished experts at-tracted clinicians, general practitionersand nutritionists alike. They learned thatthe intestinal microbiota (formerly calledgut flora) can rightly be regarded as awhole organ in itself, including the in-credible amount of at least 1014 bacteriaweighing between 1.5 and 2kg.

ts saGut microbiota can be regarded as a new organ

A fascinating yet previously unknown diversity of life forms has been discovered,

not in outer space but inside our bodies. Myriads of bacteria symbiotically living

within the human gut form a biological society that profoundly influences our

health. The 1st World Summit on Gut Microbiota for Health (2628 March 2012,

vian/France) provided physicians, nutritionists and specialist journalists with new

insights into a most promising field of cutting-edge research.

ex aInterview with Professor

Fernando Azpiroz

(Autonomous University

of Barcelona, Spain)

eight million geneSAs Prof. James Versalovic (Baylor Collegeof Medicine, Houston, USA) pointed out,this abundant variety of life forms com-prises more than 1,000 bacterial species

The hoTel royal at vian Resort where workshops of the 1st World Summit on

Gut Microbiota for Health were held.

contentTruly interactive: in vian, old-fashioned lecturing was abandoned ................ 3Birth shapes gut microbiota: mode of delivery can make a difference............ 4Intricate interplay: immune system and gut microbiota are intertwined........ 5Rich harvest: gut bacteria help getting the most out of food ............................ 6Diet the driving force:unhealthy food triggers nutritional diseases via gut microbiota ...................... 7The potential of probiotics: promising outlook but many open questions..... 8

A Section of the europeAn Societyof neurogAStroenterology And motilityMember of UEG

Prof. Azpiroz, it is only recently that the

Gut Microbiota & Health Section wasfounded as part of the European Society

of Neurogastroenterology and Motility

(ESNM). What were the motives?

Prof. Fernando Azpiroz: Within our soci-ety, we have for a long time been con-cerned with the interaction between thegut and the brain but it was not until afew years ago that it became apparentthat there was a third player to be takeninto account: the gut microbiota. We in-tegrated this new organ in our frame-

work, so that we now speak of themicrobiome-gut-brain axis, which is bidi-rectional in terms of cause and effect.Due to the medical importance of thesefindings, we felt the need to create a sec-

Prof.

fernando

azPiroz,

Chairman of

ESNMs Gut

Microbiota& Health

Section

Continued on page 2 Continued on page 3


2/8

Prof. Versalovic and Prof. Dor presentedthe audience with a variety of recentstudies showing the tight interplay

between the gut microbiota and a broadvariety of malfunctions. Nutrition-relateddisorders, inflammatory bowel diseasesand certain allergies can oen be linkedto varying compositions of the intestinalmicrobiome. A better understanding ofthe gut microbiota will therefore provideinformation essential for improving dietsand efficiently dealing with diseasessuch as obesity, metabolic syndrome,food intolerance, ulcerative colitis or IBS.

Analysing the microbiota might also

allow to predict an individuals risk to de-velop gut diseases.

As mental processes are also affectedthrough communication paths betweenintestine and central nervous system,even the treatment of certain mentaldisorders is likely to benefit from the on-going research. Though, in order to makeuse of this huge diagnostic and thera-peutic potential, much basic and clinicalresearch remains to be done. But Prof.Versalovic and Prof. Dor le no doubtthat the answers to the still open ques-tions will soon improve the prevention,diagnosis and treatment of a broad rangeof gastrointestinal diseases in manyways.

Page 2

The gut microbiota is

extremely complex and diet

influences the microbiota

composition. We have lots of

evidence that the microbiota

composition is associated

with health.

and consists of 10 times more cells thanthere are human cells in the body. So far8 million genes of bacteria living inhuman intestines have been catalogued.Thus, the gut microbiotas metagenome

the so-called microbiome turns out

to be much more diverse than the humangenome with its 23,000 genes and doesin fact form a second genome har-boured by the human gut.

Unlike human genes, however, thegut microbiome is not inherited geneti-cally as we are all sterile at birth. Thecomposition of the microbiota and itsequilibrium is strongly influenced byconditions of birth, diet or intake of an-tibiotic drugs. But recent studies showthat, in spite of all individual differences,

the worlds human population can be di-vided into not more than three en-terotypes classes which are defined bythe domination of certain species withinthe individuals intestinal bacterial pop-ulation. These enterotypes are not re-lated to nationality, age or gender.

remArkAble Scientific progreSS

The remarkable scientific progress thathas been made during the past years re-garding the gut microbiota is largely due

to innovative research techniques. Theseallow to investigate in detail large num-bers of samples of microbiotal DNA as

well as individuals interactions betweenhost and microbes, as Prof. Jol Dor(INRA / French National Institute for Agri-

cultural Research, France) pointed out.Until recently, microbiota bacteria couldmostly be studied only under laboratoryconditions, which meant considerable re-strictions as around 60% of bacterialspecies will not grow in such an environ-ment. Important insight is also gained bytransferring bacteria of healthy and dis-eased individuals into the colons of ani-mals which are germ-free (i.e. withoutgut microbiota) in order to observe theeffects on the animals health. By consid-erably accelerating the technological ca-

pacity and extending the state-of-the-artknowledge during the past decade, mi-crobiota research has become one of themost exciting fields of cutting-edge sci-ence within gastroenterology. The cur-rent dynamics of scientific activity arereflected in the fact that nearly one thirdof the 1,600 publications on the intes-tinal microbiota listed by PubMed since1977 appeared in 2011.

huge impAct on heAlth

All this has a huge bearing on our healthas the microbial activities are stronglylinked with the whole human body. Both

S r26-28 March 2012


1s t Wo rl d S u m m it " Gu t M icro b io ta fo r Heal th "


Prof.

James

VersaloViC,

Baylor

College ofMedicine,

Houston,

USA

Prof.

Jol dor,

INRA,

Jouy-en-

Josas,

France

la GranGe

au laC,

the venue

for the

summits

plenary

sessions

B

ertrandNicolas-IN

RA


3/8


Page 3

The summits attendees already be-came aware at the registration deskthat this was going to be a truly in-

teractive event: everyone was handed aSpotMe device. The small black box,which provided the names, photos andsome basic professional features of allparticipants at the touch of a few but-

tons, accompanied the attendees allthrough the conference: it enabled themto locate colleagues, send messages, ex-change information and arrange meet-ings. In addition, a particularly usefulfunction allowed speakers and audienceto communicate during the talks and pre-sentations.

The organisers of the event hadabandoned the old-fashioned lecturewith the audience just passively listeningto the expert. Due to the fact that micro-biota research is a newly emerging areawith stakeholders from very differentbackgrounds and with diverse expecta-tions, they relied on formats which stim-ulated discussions and the exchange of

t aIn vian, old-fashioned lecturing was abandoned

At the 1st World Summit on Gut Microbiota for Health, gastroenterologists met

with biologists, nutritionists and experts from various other fields. Together they

shared the experience of three days filled with inspiring information exchange,

thought-provoking discussions and open-minded interdisciplinarity. This outcome

was made possible to a large extent through the interactive character of the

events formats.

different points of view. At the beginningof the conference, round tables featuringexperts from the various fields served tomake the audience familiar with the cur-rent state of research while ample timewas allotted to questions and comments.This input from the participants, comingvia SpotMe as well as Twitter, provided

the speakers with valuable informationon the background knowledge and thedemands of their audience. That in turnhelped them design the workshops tak-ing place on day two of the conference according to the needs of the attendees.These workshops, being the second mainformat of the summit, allowed focusingon certain selected aspects. Here, theemphasis on interactivity was evenstronger as discussions and workinggroups held centre stage. Once again,SpotMe came in handy: it allowed theworkshop leaders to direct standardisedquestions to all participants concerningtheir opinions and experiences usefulinput to build the presentations on.

This summit was really

an exchange of the opinion

leadersof the world. That

must be useful for the

planning and direction ofresearch in this important

fieldin the future.

The summiTs ParTiCiPanTscould use the SpotMe device to communicate with the speakers

S r26-28 March 2012



tion which deals specifically with thisissue and which is open to everybodyworking in the field.

What are the goals of the section?Prof. Fernando Azpiroz: Our main activi-ties comprise education, information dis-semination and, of course, healthcare aswe want to translate scientific knowl-edge into clinical application for the pa-tients benefit.

How did the idea of the 1st World Summit

come into being?

Prof. Fernando Azpiroz: This meeting wasthe first major action that was taken by

our section and it was prepared within avery short period of time. With so manyexciting developments being under wayright now, we felt the urge to react andprovide a platform for high-quality infor-mation and exchange.

Have your expectations been fulfilled?

Prof. Fernando Azpiroz: Absolutely. Par-ticularly well received was the format ofthis meeting, which was quite unique in-sofar as we placed strong emphasis onthe overall interaction between partici-

pants and speakers. Another particularityof the event was that the excellence ofthe speakers was matched by that of theattendees. The success of this event en-couraged us to prepare a 2nd summit forspring 2013, to be held in Spain.

Interview continued from page 1


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Page 4

In most cases the bacterial colonisa-tion of the gut starts with the babyspassage through the birth canal. How-

ever, with children who are delivered bycaesarean section the situation is some-what different. Their intestines are initiallycolonised by environmental microbesfrom their mother, the air, and the nurs-ing staff. According to Prof. Olivier Goulet(Necker Hospital for Sick Children, Paris,France), these differing birth conditions

have important consequences: vaginally-delivered infants receive more of thebeneficial bacteria which provide shelteragainst diseases, help extracting nutri-ents and support the maturation of theintestinal mucosa. Most prominentamong these is Bifidobacteria, a speciesthat helps to produce certain vitamins aswell as to protect against immune andnutritional disorders.

At the same time, the guts of cae-sarean-delivered babies contain a higheramount of less beneficial or even poten-tially harmful bacteria, one examplebeing Chlostridium perfringens, a typethat might cause infections. In a similarway, breastfeeding offers better condi-

b sas aMode of delivery can make an important difference

Whether a baby is delivered vaginally or by caesarean section, whether it is breast-

or formula-fed has great impact on the colonisation of the gut. The consequences

for the individuals well-being may be far-reaching, even in adulthood.

tions for a balanced and healthy micro-biota than formula feeding.

birth conditionS And diSeASeS

How important these starting conditionsmay be is shown by studies which statis-tically link caesarean delivery and for-mula feeding as well as antibiotictreatment in early childhood to an in-creased risk for IBD, digestive disordersand allergies. The precise causal rela-

tions, however, remain to be clarified.Prof. Goulet points out that parents ofcaesarean-delivered or formula-fed chil-dren need not be alarmed, though, as thedeficits of these microbial populationsare oen levelled out aer around sixmonths. Nevertheless, caution andawareness are advisable as the colonisa-tion of the infants gut already givesshape to the composition of the micro-biota in later years. At around one year ofage, the childs intestinal microbiota al-ready starts to resemble that of a youngadult. A well-balanced gut microbiota iskey in preserving ones well-being, saysProf. Goulet. The foundations for this arelaid very early.

What the summit did best was

to summarise a broad range of

topics. I did not know as much

about the paediatric side of

things, about the initiation ofthe microbiome and things

that might influence that.

Prof.

oliVier

GouleT,

Necker

Hospital for

Sick Chil-

dren, Paris,

France,

at the Gut

Microbiota

for Health

summit

S r26-28 March 2012



Apart from birth conditions, anotherfactor in putting a healthy compositionof the gut microbiota at risk has emergedduring the past decades. According toProf. Goulet, the highly improved hy-giene in western countries, which hasdecreased the number of infectious dis-eases, also has its down side: as the ex-posure to microorganisms during infancyhas been significantly diminished, the

immune functions, which depend heav-ily on the intestinal microbiota, developinappropriately in a growing number ofindividuals. The result has been an in-crease in immune disorders such as IBD,asthma or type 1 diabetes.


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Page 5

Why do we not all develop in-flammation as we all harboursuch a huge amount of bacte-

ria, including potentially harmful ones,inside our intestine? Prof. Balfour Sartor(University of North Carolina, USA) tookthis question as a starting point to out-line the complex interactions betweengut microbiota and immune system. Nor-mally the gut serves as an efficient bar-rier against bacteria and their productsas it consists of several layers of defence.These include the mucus, the epithelialwall and the intestinal immune system,which functions through complex inter-actions of cellular signalling pathways

that stimulate the immune response. Asmuch as 70% of our immune cells are lo-cated in the gut.

By no means all bacterial species areharmful to the host, as Prof. Sartorpointed out. Some are neutral or evenprotective. These beneficial functions in-clude the direct inhibition of pathogengrowth, the depletion of pathogens nu-

ia aImmune system and gut microbiota are tightly intertwined

The immune system and the gut microbiota interact to protect the body against

hostile intruders. However, when immune functions fail, it may lead to inflamma-

tory conditions such as ulcerative colitis or Crohns disease. Growing insight into

the interplay between immune cells and bacteria will help to establish therapies

which are based on supporting the beneficial species of the gut microbiota and

on correcting defective immune signalling pathways.

trients or the stimulation of immune re-sponses. The gut immune system and gutmicrobiota work closely together as theintestinal cells immune responses con-

trol and shape gut bacteria into commu-nities that help defend the body againstdisease-causing invaders.

inflAmmAtory conditionS

A product of interAction

However, when gut barrier functions fail,it may lead to inflammatory conditions.In certain cases of Crohns disease, a mal-

My first impression of

the summit is its quite

high level. There are many

experts here from different

fields. I learned that the

gut microbiota is some kind

of ecosystem because its

quiteon its own. And the

more diverse it is, the more

stable it is.

a Well-BalanCed miCroBial ComPosiTionis key in preserving gut health.

S r26-28 March 2012



function of the NOD2 gene induces anoverreaction of the immune systemagainst several bacterial components.

We believe that Crohns disease is aproduct of interaction between geneticsusceptibility, environmental factorssuch as diet or antibiotic treatment andcertain bacteria that provide antigenswhich drive an immune response that inthe end leads to the disease, says Prof.Sartor.

In the healthy individual, the compo-sition of the microbiota is very diverse,including a high level of protective and alow amount of potentially harmful

species. In patients with ulcerative colitisand Crohns disease, the general diver-sity is lower and the proportion of bene-ficial and pathogenic bacteria isreversed.

better underStAnding

improved treAtment

According to Prof. Sartor, translating thebetter understanding of the gut micro-biota interaction into better and less ag-gressive treatments will include theselective elimination of detrimental bac-teria while at the same time preservingor enhancing the protective bacterialspecies as well as correcting defectiveimmune signalling pathways.

Prof.

Balfour

sarTor,

University

of North

Carolina,

USA


6/8


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Page 7

Prof. Colin Hill (University CollegeCork, Ireland) and Prof. Jan Tack(University of Leuven, Belgium)

presented the audience with a numberof studies which reveal that obese andlean individuals carry a clearly distinctgut microbial composition. In obese indi-viduals, the efficiency of energy harvest

is particularly high while mechanisms es-sential for controlling food intake are dis-turbed. Two main groups of gut bacteriaare known to be responsible: Firmicutes,which are capable of extracting and stor-

d Unhealthy food triggers nutritional diseases via gut microbiota

Metabolic disorders such as obesity or diabetes are triggered by several

factors among which the interaction of diet with the digestive functions of the

gut microbiota plays a key role. Healthy and diverse food intake significantly

influences the gut microbial composition and thus the health status.

ing energy from otherwise indigestiblealimentary components, and Bacteroi-detes, the function of which is somehowopposed as they encapsulate carbohy-drates which are then being excreted. Inhealthy individuals, the occurrence ofboth species is more or less balanced,while in those suffering from obesity, the

Firmicutesoutnumber the Bacteroidetes,thus causing a considerable gain ofweight and fat mass through an over-effi-cient energy extraction. How tightlychanges in diet, body weight and gut mi-crobiota composition are linked hasbeen shown by utilising mice which werefed a high-fat diet. Within a short periodof time, the food intake increased the rel-ative abundance ofFirmicutesat the ex-pense ofBacteroidetes. But aer shiingback to the original diet, the changes inthe microbial composition were reversed.Similar results have been gained throughexperiments with microbiotas from leanand obese mice being transplanted intothe colons of germ-free mice.

This very exciting areais

in its infancy. I think were

just at the beginning of

understanding the impor-

tance of the gut microbiota

and its relevance tohuman

disease.

links BeTWeen GuT BaCTeria and healThprovide a promising field for research.

S r26-28 March 2012



loSS of diverSity cAuSeS

diSeASeS

While it is beyond doubt that gut micro-bial composition, diet and health statusare associated, the causal direction be-tween them is still a matter of discussionand further research. According to Prof.Tack and Prof. Hill, the current state of re-

search seems to point to diet as the maindriver in changing health conditionswhile the gut microbiota has an amplify-ing effect. Evidence is being provided,among other findings, by an ongoing in-vestigation of food intake and other lifestyle factors of elderly people in relationto their gut microbial composition andhealth status. The results that have beengained so far support the claim that asthe food gets less healthy and less di-verse, the gut microbial composition fol-

lows, said Prof. Hill. This loss of diversitycan not only trigger digestive disorderssuch as obesity and diabetes but proba-bly inflammatory bowel diseases, aller-gies and mental disorders too.

Prof.

Colin hill,

University

College

Cork,

Ireland

Prof.

Jan TaCk,

University

of Leuven,

Belgium

ViolaineRochet-INRA


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Page 8

Probiotics have attracted public at-tention for quite a long time. Al-though their principally beneficial

role is undisputed, there are still manyaspects under scientific discussion.These regard the precise effects of pro-biotics considering various conditions aswell as how to employ probiotics mostefficiently for prevention and treatment.

The most compelling evidence forthe impact of probiotics in patients with

bowel function disorders is their effecton gas-related symptoms such as bloat-ing and flatulence, said Prof. MagnusSimrn (University of Gothenburg, Swe-den). Another promising field for appli-

t a sPromising outlook but many open questions

Probiotics can help in the treatment of a number of GI conditions such as gas-

related disorders, diarrhoea or IBS. However, in many cases the precise effects as

well as the most efficient modes of clinical application remain to be clarified. This

also affects the question which kind of evidence is needed to establish a public

health claim for food containing probiotics.

cation is abdominal pain: patients with ahigh degree of pain were shown to havea low proportion of Bifidobacteria, one ofthe most prominent bacterial strainsused as probiotics, and vice versa. Probi-otics have similar beneficial effects ondiarrhoea associated with antibiotics:studies show that this condition can beprevented to a large extent through pro-biotic products. With regard to acute di-arrhoea in children, the results are

somewhat mixed: although certain pro-biotic preparations reduced the durationof the disease and improved the stoolconsistency, they had no effect on feverand vomiting.

helpful AgAinSt ibS

An extensively researched area is the im-pact of probiotics on IBS. As Prof. Simrnpointed out, probiotics can affect differ-ent factors that are responsible for IBSincluding the intestinal barrier, neuromo-tor functions, gut-brain functions andvisceral hypersensitivity. Many clinicaltrials show some kind of effect. But thereis still insufficient evidence as to whichprobiotic should be given to which pa-

S r26-28 March 2012



tient, says Prof. Simrn. With regard toinflammatory bowel diseases, accordingto him, so far probiotics have not provenvery successful compared to other treat-ment options.

The various research issues which areawaiting further investigation raise thequestion of what kind of evidence isneeded to establish a health benefit forprobiotics. Dr Mary Ellen Sanders (Davis,USA) tackled this question with regard toprobiotics that are not adminstered asdrugs but included in food. She pointedout that companies wishing to communi-cate health claims on the labels of theirprobiotic products have to meet ratherstrict regulations as the EU requires evi-dence based on scientific assessment of

the highest possible standard. The resultis that the great majority of health claimsis rejected. One possible solution mightbe to accept different grades of evidencewhile at the same time informing theconsumer which of these standards ismet by the respective products.

dr mary

ellen

sanders,

Davis, USAProBioTiCsare oen included in dairy products.

C

laudioBaldini-Fotolia.c

om

Prof.

maGnus

simrn,

University of

Gothenburg,

Sweden

The main message is that

everything concerning pro-

biotics isvery promising.

Publisher: Gut Microbiota & Health Sectionof ESNM Concept & Execution: impressumhealth & science communication Layout:Kerstin Wendel

A Section of the europeAn Societyof neurogAStroenterologyAnd motility

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