Microbes for Health 2011

Bottom up signaling : can intestinal microbes affect brain function and behaviour in Humans ? - Fouad Boumezbeur

Cf. Bercik et al., 2011 ; Neufeld et al., NGM, 2011 - Fouad Boumezbeur

pathogen initiated interoceptive signals from the gut can enhance anxiety-like behaviour via vagal afferents - Fouad Boumezbeur

indirect clinical evidence for an important role fo intest pathogenic micrb to brain signaling in humans : acute gastroenteric infection are associated with strong negative emotions and major recution in motivational drive, and also dopamine signaling - Fouad Boumezbeur

Q : could commensal play a role un background emotions ? - Fouad Boumezbeur

Q : could probiotics beneficially affect gut to brain signaling ? - Fouad Boumezbeur

functional and neuroplastic brain change caused by stress may induce ACTH peak activity, inducing production of glucocorticids and catecholamines - Fouad Boumezbeur

discovery of the brain networks with relevance to gut brain interactions : homeostatic afferent network and emotional arousal network ! : Cf. Mayer, 2009 - Fouad Boumezbeur

Does chronic probiotic ingestion alter brain activity and responsiveness to emotional stimuli ? - Fouad Boumezbeur

it's much easier in California to conduct this kind of study than a drug study. - Fouad Boumezbeur

subject population : healthy women aged 18-50 - Fouad Boumezbeur

study overview : active product vs placebo --> functional MRI (5 min scan of brain, resting state activity), emotion reactivity and emotion induction tests were conducted at different times during the study period --> Whole-brain imaging comparisons - Fouad Boumezbeur

results of emotional induction and emotional reactivity analysis : overall, considerably more activity was observed in controls compared to the probiotic group - Fouad Boumezbeur

region of interest : reduced acitvity in primary interoceptive cortex in probiotic group - Fouad Boumezbeur

insula connectivity analysis : during negative emotion matching task, what connectivity patterns are different in the post-treatment Activia group ? - Fouad Boumezbeur

amygdala connectivity was studied too - Fouad Boumezbeur

results : there is a possible communication channel between gut microbiota and brain - Fouad Boumezbeur

Visceral Pain Responses : Effect of commensal bacteria - Fouad Boumezbeur

mouse model - Fouad Boumezbeur

Cf. Kamya et al. - Fouad Boumezbeur

effect of L. reuteri on HR response - Fouad Boumezbeur

the myenteric plexus preparation is used to record activity of enteric neurons (in situ Patch clamping of enteric neurons), in order to study the effects of commensal organisms on visceral pain perception. - Fouad Boumezbeur

effect of Lactobaccilus feeding on enteric nerve excitability : calcium-activated potassium channel - Fouad Boumezbeur

Gardos channels are present in erythrocytes, T cells and mast cells (MCs) - Fouad Boumezbeur

DCEBIO activates this channel - Fouad Boumezbeur

TRAM-34 reduces sAHP and excites IPANc - Fouad Boumezbeur

Hemidissection platform of the mucrosal layer and the myenteric plexus : probiotic effect depends on nerve conduction from epithelial cell layer - Fouad Boumezbeur

bacterial capsular polysacc down reg inflammation : Cf. Mazmanian et al. - Fouad Boumezbeur

JB-1 , B. fragilis or PolySacc A applied to epithelial ALL excite IPANc : increased number of action potential responses to standard depolarizing test pulse - Fouad Boumezbeur

organ bath motility platform dispositive : perfuse of the mucosal layer with bacteria+ Krebs metabolites vs Krebs metabolites only - Fouad Boumezbeur

L. rhomnosus (JB-1 strain) moderates motility within minutes, as shown on a dose-responses curve - Fouad Boumezbeur

this particular system was only observed with a video imaging technique - Fouad Boumezbeur

recordings of the effects of luminal JB-1 on firing frequency of mesenteric nerve bundle before and after vagotomy : the system is still excited after vagotomy - Fouad Boumezbeur

stres response in GF mice : GF show an exaggerated HPA response to ACTH - Fouad Boumezbeur

effects of L. ingestion on acute stress response (BALB/c mouse model) - Fouad Boumezbeur

enteric intrinsic primary afferent neurons in gut from GF mice are less excitable than those from control or conventional mice - Fouad Boumezbeur

Cf. paper entitled "the intestinal microbiota effect control levels of brain-derived neurotropic factor and behaviour in mice" - Fouad Boumezbeur

effects of L. ingetion on constitutive GABA receptors in the brain --> incresed anxiolytic behaviour! (do bacteria got into the brain ?) - Fouad Boumezbeur

commensal bacteria signal to the nervous system within minutes of luminal introduction via several pathways, including inhibition of neural Kca3.1 and G protein linked activation - Fouad Boumezbeur

Cf. Cryan and O'Mahony, "The microbiome-gut-brain axis: from bowel to behavior", Neurogastroenterology and Motility, 2011 - Fouad Boumezbeur

Is the ENS a forgotten player un the microbiota/host crosstalk ? - Fouad Boumezbeur

~100 billions neurons in the gut !!! - Fouad Boumezbeur

ganglia are interconnected in order to induce reflexes along the gut and control digestive processes - Fouad Boumezbeur

neurons and astrocytes are associated as control of the gut functions and are forming neuro-glio epithelial units (NGEUs) in the gut - Fouad Boumezbeur

the ENS is fully integrated within the gut (it kind of works on its own, even in the absence of the brain) ! - Fouad Boumezbeur

Pr. Neunlist demonstrates that the enteric glial cells enhance barrier protection (in vivo IECs) : glia is able to modulate immune response - Fouad Boumezbeur

gut colonization by microbiota is associated with development of colonic motility : phenotypic changes of the colonic contractile activity in GF mice - Fouad Boumezbeur

bacterial colonization is associated with major neuroplastic changes in the ENS : glial maturation is enhanced - Fouad Boumezbeur

ENS regulation and ENS phenotype may be a strain-specific effect - Fouad Boumezbeur

L. reuteri modulate ENS functions and colonic motility - Fouad Boumezbeur

but how can a bacterial strain modulate ENS, knowing that enteric neurons express TLR receptors ? - Fouad Boumezbeur

only butyrate was able to induce cholinergic phenotype : neurons are able to detect bacterial metabolites - Fouad Boumezbeur

post-natal increaase in luminal butyrate (Barat et al) - Fouad Boumezbeur

butyrate enhance ENS maturation - Fouad Boumezbeur

Conjugated linoleic acid (cLA) producing bacteria medoluate host Fatty Acid composition - Fouad Boumezbeur

Do polyunsaturated fatty acids modulate ENS and GI functions ? an INRA-INSERM colloboration is addressing this question. - Fouad Boumezbeur

TORNADO Consortium : http://fp7tornado.eu/ -- Sven Pettersson interview : http://www.dn.se/nyheter... (swedish version only) - Fouad Boumezbeur

regulation of inflammation is controlled by brain, with some receptors connected to the pain reaction brain area - Fouad Boumezbeur

an unexplored field of research : the amniotic fluid - Fouad Boumezbeur

a study published in PNAS : BNDF and NGF-1-A growth factors related to brain development - Fouad Boumezbeur

anxiety vs fear : to convert a biochemical analysis into a behaviour analysis - Fouad Boumezbeur

gut microbiota can alter mouse behaviour (Dias-Haijtz et al, PNAS 2011) - Fouad Boumezbeur

Dark-Light test : an experiment on anxiety and fear on the mouse model - Fouad Boumezbeur

Toxoplasmosis can infect mice, such as an infected mouse may feel no fear even in front of a cat ! - Fouad Boumezbeur

gut-brain axis shed light on behaviour change in the Drosophila and C. elegans models as well - Fouad Boumezbeur

Gut microbiota modulate the Blood-Brain barrier (Maha Al-Asmakh) - Fouad Boumezbeur

Regulation of molecular flows : who is allowed in ? - Fouad Boumezbeur

in order to answer this question, the role of astrocytes and BBB are being studied intensively. - Fouad Boumezbeur

small molecules are tracked down using in vivo PET imaging - Fouad Boumezbeur

ventral palidum and anterior amygdala PET imaging in GF and SPF animals show that the PBS treated SPF mice show a change in BBB permeability, compared to GF mice, confimed by in-vivo imaging of blood vessls in SPF mice. - Fouad Boumezbeur

search for SCFA (acetate, butyrate and propionate) as an evidence of a gut-associated BBB permeability - Fouad Boumezbeur

SCFA dosage : a particular gut microbiota, or maybe just a single bacterial species is responsible for the regulation of the BBB permeability. - Fouad Boumezbeur

gut microbiota can regulate TJP in BBB of GF mice, and SCFA and gut microbiota can ameliorate leakiness of the BBB.in GF mice. - Fouad Boumezbeur

drastic envirnmental changes could be linked - Julien Tap

will focus on gut microbiota, dysbiosis ? - Julien Tap

a lot evidence of dysbiosis on Crohn disease (CD) - Julien Tap

(dysbiosis : it's a concept saying that gut microbiota composition and function chages compared to normal microbiota) - Julien Tap

there is a decrease in diversity in CD patient - Julien Tap

PCA cluster CD patient together - Julien Tap

with a concordance with host transcriptome activity - Julien Tap

is there a loss of host-microbiome crostalk in CD patient ? - Julien Tap

(citation of our diabetes journal paper !) - Julien Tap

meatbolism (fat mass) is correlated with Bacteroides (-), E.coli (-) and Bifido (+) - Julien Tap

update result from 454 pyrosequencing data - Julien Tap

correlation between transcritome and microbiota - Julien Tap

now focus on Feacalibacterium Prauznitzzi (F.prau) - Julien Tap

Joel cite work of Harry Sokol (a link between F. prau and inflammation) - Julien Tap

a bioactive compound is almost isolated from F.prau by Langella team - Julien Tap

let's switch to functional (screening) metagenomics ! - Julien Tap

a lot of clone candidate which could stimulate different host metabolic or inflammation pathway - Julien Tap

Joel talk about a collab with Maria Rescigno , dendritic cells used for metagenomics screening - Julien Tap

is prebiotic is relevant in the context of obesity ? - Julien Tap

Bifido are an interersting candidate to interact with prebiotics - Julien Tap

inulin for example prone to increase of bifido (still mice obese model) - Julien Tap

is metabolic changes produced by prebiotic is link to microbiota , - Julien Tap

SCFA are provinding energy and act as metabolic regulators - Julien Tap

microbial receptors in adipocytes tissue participate to adiposity - Julien Tap

which bacterial metabolits could play role with the interaction of adipose tissue ? - Julien Tap

(focus on PPAR-gamma) - Julien Tap

adipose tissue produce and secret leptin - Julien Tap

prebiotic increase sensitivity to leptin (know as satiety hormone) - Julien Tap

is it related with gut microbes ? - Julien Tap

Are bifido the main target of prebiotic ? - Julien Tap

(citation of our diabetes paper ...) - Julien Tap

increase in LPS level is related to fat intake - Julien Tap

prebiotics impact on cytokines - Julien Tap

Prebiotic could improve junction between gut cells (gut barrier) - Julien Tap

prebiotic play a positive role on the metabolism of Poly unsaturated fatty acid - Julien Tap

most important factor is the localization in the intestine (colon vs ileon vs jejunum) - Julien Tap

colonocytes of conventionally raised myd88 defincient mice have got more norovirus - Julien Tap

hypothesis : microbiota, diet and host genotype are linked by metabolic phenotypes - Julien Tap

SCFA could be linked to lipogenesis on the liver - Julien Tap

Gut microbiota supresses Fiaf expression in the small intestine (famous gordon lab paper in PNAS) - Julien Tap

Fiaf promotes fatty acid oxidation - Julien Tap

gut microbiota could also impact inflammation in gut tissue - Julien Tap

Blood glucose is also influence by the presence of gut microbiota - Julien Tap

LPS in important for the macrophage recruitement in adipocytes tissue - Julien Tap

how artherosclerosis is linked with gut and oral microbiota ? - Julien Tap

More enterotype 3 (ruminococcus) in Artherosclerosis patient - Julien Tap

Mass spectra could be used as variable for Principal component analysis - Julien Tap

Microbiota seems to be linked to a bunch of disorders, this could be leads to personalized medicine - Julien Tap

what is the impact of microbiota on normal physiology and influence on risk exposure ? - Julien Tap

Microenvironment influences the metabolic phenotypes in Rats - Julien Tap

Germ free vs conventional Rats have a different metabolites profile in kidney, liver and heart - Julien Tap

lets focus on RYGB in Rat model - Julien Tap

after gastric bypass (RYGB) there is in change in microbiota and metabolites profiles (increase in Proteobacteria) - Julien Tap

some microbial species (454 sequencing) correlates with metabolites - Julien Tap

Metabolic in host is is affected by pre and probiotic intake - Julien Tap

introduce now : liver-gut-brain axis - Julien Tap

Austism children have a different metabolic profile in urine - Julien Tap

Biomarkers from gut microbiota co-metabolome may identify autistic children - Julien Tap

Brain metabolites are also influenced by microbiota (germ free vs control mice) - Julien Tap

let's focus on preterm birth now - Julien Tap

Differential biomarkers are associated with preterm birth (urine NMR) - Julien Tap

how microbiota reposnse to high or low fat diet - Julien Tap

microbiota is shaped by diet over time (we talked about mice and very control diet here) - Julien Tap

Blaser focus now on Helicobacter pylori as model of metabolism interaction with the host - Julien Tap

(H. pylori is a pathogens which cause ulcer and stomach cancer) - Julien Tap

H.pylori prevalence decrease in US people since decades now - Julien Tap

H.pylori in stomach is linked to a bunch a metabolism parameters (H.pylori free stomach vs H.pylori present in stomach) - Julien Tap

Ancient stomach dominated by H. pylori is prone to gastric cancer while post modern is to GEJ adenocarcinoma - Julien Tap

how antibiotic interact with microbiota and metabolism parameters ? (still in mice as model) - Julien Tap

STAT (leptin deficient) mice vs control mice - Julien Tap

different in weight gain as expect now let's check antibiotic - Julien Tap

with antibiotic low decrease of alpha diversity in microbiota - Julien Tap

STAT mice change Short chain fatty acid in cecal content in mice - Julien Tap

genes are regulated in the liver as well - Julien Tap

model proposition : anitbiotic change composition of microbiota which impact SCFA production and regulate gene on the liver - Julien Tap

epidemiological point of view : is antibiotic pulse in early life change microbiota ? - Julien Tap

mice treated with pulse of antibiotic, gain more weight than control in early life - Julien Tap

Bacteroidetes/Firmicutes ratio seems to change according the antibiotics intake - Julien Tap

All sequences analysis is done in collab with George Weintstock - Julien Tap

q by Lipin Zhao: insulin-resistance and antibiotics ? yes, we have evidence of that in couple of our experiment - Julien Tap

Marc Daëron talks about Lactobacillus casei used by Danone in the yoghurts - Rayna

myeloid cells, polynuclear, with four different lineages (neutrophils, acidophils, basophils, eosiphils), can deal with the pathogens and adapt the immune response by presenting the antigen (e. g. an allergen) to T cells that will lead to differentiation of B cells and will result on a large production of antibodies, These mast cells will recruit the immunoglobulins (Ig). This is the effector phase, which leads to the pro-inflammatory response. - Fouad Boumezbeur

L. casei inhibits IgG-dependent passive arthritis - Fouad Boumezbeur

mast cells are involved in IgE-dependent passive systemic anaphylaxis and IgG-dependent inflammation - Fouad Boumezbeur

Marc Daëron presents some findings published in September here http://t.co/4Jx5lbU3 (via @juliantap ) - Rayna

L. casei inhibits IgE-dependent and IgG-dependent mast cell activation, however inhibition is not due to mast cell death or activation during exposure to the bacteria - Fouad Boumezbeur

L. casei inhibits the Lyn/Syk/LAT pathway - Fouad Boumezbeur

but not the NF-kB pathway ! - Fouad Boumezbeur

L.casei does not have to be alive to have beneficial effects - Fouad Boumezbeur

screening of 40 L. casei strains : these strains greatly differ in their morphology - Fouad Boumezbeur

In the mouse model, Citrobacter rodentium extracellular infection can naturally occur in the large intestine - Fouad Boumezbeur

7 days after infection (C57BL/6 mice) : C. rodentium are not alone ! - Fouad Boumezbeur

th enormal composiiton is disturbed during the infection --> in particular, after 7 days, lots of alpha-protobacteria are detected (transient community?) - Fouad Boumezbeur

diarrhea --> oxygen availability - Fouad Boumezbeur

differen thost susceptiblity to C. rodentium infection were observed, most of the mice survive - Fouad Boumezbeur

yet, no genetic determinant have been found - Fouad Boumezbeur

analysis of faecal transfer of microbiota using T-RFLP - Fouad Boumezbeur

differential microbiota can be transferred : microbiota can control host susceptibility! --> transferring the susceptible microbiota into resistant mice makes them more susceptible - Fouad Boumezbeur

How? --> IL-22 and Reg-3 beta are upregulated in resistant animals - Fouad Boumezbeur

impact of the microbiota on the chemical composition of the GI tract ? - Fouad Boumezbeur

method : collect faeces --> extraction of fecal metabolites --> metabolic pathways - Fouad Boumezbeur

levels of several hundred faecal metabolites and multiple host metabolic pathways are affected by antibiotic treatment - Fouad Boumezbeur

role of the microbiota in asthma : the hygiene hypothesis : do we live too cleanly in childhood in developed countries ? - Fouad Boumezbeur

industrialized countries : 22-32% children under 10 - Fouad Boumezbeur

epidemiologicval evidence: large birth cohort studies reveal gut microbiota differs between allergic and non-allergic infants - Fouad Boumezbeur

do antibiotic-induced shifts in microbiota affect asthma susceptibility ? - Fouad Boumezbeur

results in mouse model : neonatal antibiotic treatment affects asthma severity --> lung inflammatory, lung pathology, AHR, IgE, Eosinophils - Fouad Boumezbeur

large variation of the mb composition between Antibiotic treatments - Fouad Boumezbeur

Vancomycin treatment : profound gut alteration ! - Fouad Boumezbeur

what are the bacterial taxa that correlate with exacerbated asthma ? - Fouad Boumezbeur

Conclusion : Antibiotics can be used to differentially shift microbiota, microbiota can affect susceptibility to enteric infections and host resistance. - Fouad Boumezbeur

Crohn Disease (CD) colon tissue ... burk! - Fouad Boumezbeur

dealing with the environment change in IBD risk - Fouad Boumezbeur

history of the eradication of Helminths : Hookworm eradication was initiated in 1905, it is no longer epidemic in USA nowadays - Fouad Boumezbeur

similar decline observed for other helminths --> Helminths influenced human immune gene variation - Fouad Boumezbeur

Loss of helminths is an environmental change that have contributed in IBD risk increase - Fouad Boumezbeur

model : Helmosimodies bakeri (Nematodes) - Fouad Boumezbeur

H. bakeri exposure alters GALT cytokine expression - Fouad Boumezbeur

its exposure actively inhibits GALT T cell IL 17 via IL-10 and IL-4 - Fouad Boumezbeur

helminth exposure affects cytokine production by MLN cells from Stat6KO mice - Fouad Boumezbeur

H. bakery doesnot reverse colitis in Rag reconstituted in Stat6KO mice - Fouad Boumezbeur

H. bakeri exposure have an effect on cytokine in Stat6KO transfer colitis - Fouad Boumezbeur

other models of Helminth regulation mechanism are available - Fouad Boumezbeur

helminths alter host response to bacterial pathogens, Helminth colonization may alter intestinal microbiota --> benefit to bacteria - Fouad Boumezbeur

another tested model : porcine whipworm (Trichuris suis) - Fouad Boumezbeur

a CD open Label Trial case/control study and an UC study were conducted - Fouad Boumezbeur

UC trial results : all the components of the score improved in patients who were given T. suis, compared to patients who were given placebo - Fouad Boumezbeur

Case report : E. vermicularis in UC --> Cf. Broadhurst et al., Sci. Transl. Med, 2010 - Fouad Boumezbeur

Case report : T. suis in UC --> Cf. Broadhurst et al., Sci. Transl. Med, 2010 - Fouad Boumezbeur

T. suis ova in Allergy : Patients with helminths have lower allergen response (Cf. Smits, Curr. Allergy Asthma Res., 2010) - Fouad Boumezbeur

T. suis ova in multiple sclerosis : Patients with MS and helminths have attenuated course - Fouad Boumezbeur

Open label safety limb of HINT trial (Fleming et al, Mult. Scler. 2011) - Fouad Boumezbeur

Markers for autophagy : LC3-puncto and LC3-II formation - Fouad Boumezbeur

bacterial infection can induce autophagy, e. g. some Shigella bacteria strains - Fouad Boumezbeur

autophagy acts as a selective system for pathogens via cargo receptor - Fouad Boumezbeur

Shigella-targeting autophagosomes : delta-icsB Shigella bacteria are sentitive to autophagy. - Fouad Boumezbeur

Atg5 (autophagy protein) and virulence protein VirG are both localized at one pole of Shigella : VirG is essential for the autophagy targeting Shigella, Afg5 targets VirG for Shigella-targeting autophagy - Fouad Boumezbeur

the Tecpr1 protein is essential for autophagic degradation of Shigella : formation of a Tecpr1-Afg5-VirG cargo receptor. How can this complex get anchored to the membrane ? - Fouad Boumezbeur

results : Tecpr1 is anchored to Shigella-targeting autophagosaomes by WiPi-2 and Ptdlns - Fouad Boumezbeur

autophagic recognition of VirG --> Afg5-VirG interaction is competitively inhibited by icsB in a dose-dependant manner - Fouad Boumezbeur

bacteria play a crucial role in IBD : antibiotics ameliorate symptoms in humans and animals - Fouad Boumezbeur

germ-free animals do not develop IBDs in several models - Fouad Boumezbeur

no definitive pathogens have been identified yet, or maybe it is just a question of tolerance over micro-organisms ? - Fouad Boumezbeur

dysbiosis : a major feature of the IBD-associated microbiota - Fouad Boumezbeur

E.g. Bacteriodetes fragilis : Gram- bacterium, obligate anaerobic, prominent commensal of the human GI tract - Fouad Boumezbeur

at least 2 polysaccharides (PSA) have a novel zwitterionic structure - Fouad Boumezbeur

PSA role in protection to chemically induced intestinal inflammation have already been assessed in the mouse model - Fouad Boumezbeur

colitis is correlated to pro-inflammatory T-helper cells proliferation and elevated IL-17 / IL-23 levels - Fouad Boumezbeur

PSA mediates the expansuion of functionally suppressive CD4+/CD25+/Foxp3+ T-regs during trinitrobenzene sulfonic acid (TNBS) induced colitis - Fouad Boumezbeur

and it directs the development of a specific gene expression for inducible Foxp3+ T-regs - Fouad Boumezbeur

protective role of PSA during TNBS colitis requires Toll-like receptor (TLR) 2 signaling - Fouad Boumezbeur

PSA transport : PSA is packaged into outer-membrane vesicles (OMVs) - Fouad Boumezbeur

Shen et al. (submitted) - Fouad Boumezbeur

OMVs protect mice from colitis in a PSA-dependant manner - Fouad Boumezbeur

gene expression profile of PSA-specific and TLR-dependant genes in dendritic cells (DC) have been obtained by analysing qPCR of the targeted genes. - Fouad Boumezbeur

Gadd45-alpha expression in DCs is required for PSA-mediated protection from colitis - Fouad Boumezbeur

wild-type DCs alone are able to complement and to protect IECs - Fouad Boumezbeur

B. fragilis occupies a mucasal niche during commensal colonization of germ-free mice ; it is beneficial at the first place. - Fouad Boumezbeur

PSA restrains Th17 responses to B. fragilis. adaptation ? - Fouad Boumezbeur

Cf. Round et al., Science 2011 - Fouad Boumezbeur

TLR2 expression on CD4+ T cells is required for in vitro IL-10 production in the presence of PSA - Fouad Boumezbeur

OMVs signal through TLR2 on DCs, unlike PSA which can directly activate CD4+ T cells - Fouad Boumezbeur

TLR2 deficient T cells are unable to restrain in vivo Th17 responses to B. fragilis - Fouad Boumezbeur

PSA is required for enabling B. fragilis to colonize the germ-free mice mucosa - Fouad Boumezbeur

a global picture as a conclusion : PSA evolved to promote mucosal toleerance during colonization by B. fragilis. - Fouad Boumezbeur

1/ functional (DNA cloning and screening) - 1985 - Fouad Boumezbeur

2/ phylogenetic (16S gene) - Fouad Boumezbeur

3/ metagenomics of annotated genes (WGS approach) - 2000's - Fouad Boumezbeur

qualitative metagenomcis reveals genetic potentials of the microbial genomes - Fouad Boumezbeur

from the sample, the abundance of reference genes can be assessed by mapping and counting reads over the reference databases - Fouad Boumezbeur

description of what is quantitative metagenomics to study human microbiome, a huge step since few years ... - Julien Tap

the MetaHIT metagenomic approach acts like a microscope - Fouad Boumezbeur

the human intestinal microbiota is still unknown, as a forgotten organ. - Fouad Boumezbeur

chronic diseases may be linked to variations of microbiota diversity and dysbiosis - Fouad Boumezbeur

extensive international collaboration is needed for integrative microbiomics - Julien Tap

the MetaHIT approach : to construct the largest gene catalogue ever, by sequencing microbiome sampled from a hundred of individuals - Fouad Boumezbeur

this gene catalogue leads to establish a classification of individuals between 3 types of microbiota composition : the enterotypes ! - Fouad Boumezbeur

enterotypes can be likened to blood groups - Fouad Boumezbeur

but the reasons for their existence remain to be elucidated - Fouad Boumezbeur

Enterotypes linked to blood group ? - Julien Tap

obesity : a case/control study of 6,784 danes - Fouad Boumezbeur

obese individuals differ from the others by their bacterial gene number (based on the MetaHIT gene catalogue) - Fouad Boumezbeur

low gene abundance suggests low bacterial diversity in most of the obese individuals - Fouad Boumezbeur

study focused on low-gene obese people - Fouad Boumezbeur

LG obese Danish women have increased inflammatory partameters - Fouad Boumezbeur

weight of low-gene obses people : no significant difference between women and men, although low-gene danes have gained more weight over the 9 years. - Fouad Boumezbeur

Dusko introduce metaspecies concept using MetaHIT "barcode" - Julien Tap

a tentative to find the species by correlating genes between individuals based on their relative abundance in metagenomic samples (quantitative metagenomics approach) - Fouad Boumezbeur

focusing on Metanogenesis pathway - Julien Tap

four meta-species may help improve diagnostic for low and high gene individuals - Fouad Boumezbeur

low diversity fo the human gut microbiota is associated to inflammation. - Fouad Boumezbeur

also, ulcerative colitis related microbiota is usually linked to low-gene abundance - Fouad Boumezbeur

12 meta-species work well as biomarkers of UC - Fouad Boumezbeur

5 relapse-associated bacterial species were found connected --> pronostic biomarkers ? - Fouad Boumezbeur

a few bacterial species are clearly associated to chronic diseases. - Fouad Boumezbeur

take-home message : the metagenomic microscope should be pointed to specific species that are likely to work as reliable biomarkers in IBD studies in a close future. - Fouad Boumezbeur

19-21 march 2012 : MetaHIT/IHMC Congress !! - Fouad Boumezbeur

glaser " microbiotyping compagny" ? - Julien Tap

why work on the elders ? - Fouad Boumezbeur

Irish population is a ageing one. - Fouad Boumezbeur

people gets significantly older and older - Julien Tap

world population average age is increasing, as life span is. - Fouad Boumezbeur

microbiota composition and activity are related to increased infection rates, but to what extent ? - Fouad Boumezbeur

Project ElderMet, for Elderly Metagenomics, focuses on Elderly Irish people - Fouad Boumezbeur

material : faecal microbiota (500 subjects > 65 yrs old) at time T0, T3 and T6 (months) during hospitalization - Fouad Boumezbeur

the subjects are coming from all over Ireland. - Fouad Boumezbeur

results : Claesson et al., 2011 PNAS, USA - Fouad Boumezbeur

the Bacteriodetes : Firmicutes ratio varies considerably in Elderly Irish people, as well as the Actinobacteria and Proteobacteria communities - Fouad Boumezbeur

compared to younger adults, the core microbiota is less diverse - Fouad Boumezbeur

yet, O'Toole et al observed a temporal stability of the faecal microbiota composition. - Fouad Boumezbeur

Is microbiota composition related to community location, diet or metadata? - Fouad Boumezbeur

UniFrac reveals a microbiota seperation based on subject location - Fouad Boumezbeur

between day hospital and rehab people ... - Julien Tap

Hierachical Clustering seperates Microbiota by community location - Fouad Boumezbeur

separation in 2 major microbiota composition types, characterized by a few known species ... what about the enterotypes ? - Fouad Boumezbeur

enterotypes in the ElderMet cohort ! - Fouad Boumezbeur

Prevotella type and Bacteroides type are the 2 major types what were predicted by HC based on the UniFrac database. - Fouad Boumezbeur

association of interest : Diet, Age and Microbiota --> should elderly people change their diet, depending on their microbiota composition ? - Fouad Boumezbeur

fermentation of dietary polyssaccharides is accomplished by microbes linked in a metabolic food web. - Fouad Boumezbeur

approach : colonize germ-free mice with sequenced species isolated from human microbiota - Fouad Boumezbeur

one of the advantage of this approach is to eliminate the uncertainty surrounding the "who's there ?" issue. - Fouad Boumezbeur

RNA-seq could lead to metabolism pathway prediction - Julien Tap

Accumulation of H2 gas decrease efficiency of fermentation - Julien Tap

colonized mice are studied by applying an INseq (insertion sequencing transposon mutagenesis) technique on GI tract samples - Fouad Boumezbeur

3 pathway known to consume H2 : Acetate, CH4 and SH2 - Julien Tap

sulfate-reducing bacteria generate hydrogen sulfate, that can be toxic in high concentrations, as an end-product of the fermentation pathway - Fouad Boumezbeur

my thought about this : Metanobrevibacter links to CH4 and coorelate with Ruminococcus, SH2 is produce by Desulfovibrio (correlating with Prevotella), Acetate could be produced by Bacteroides ... enterotypes ! - Julien Tap

one of the questions that were addressed is "how does diet affect colonization and metabolism of Desulfovibrio?" - Fouad Boumezbeur

construction of a 9-species composed microbiota in germ-free mice - Fouad Boumezbeur

Western diet promotes higher levels of D. piger and hydrogen sulfate in the distal gut - Fouad Boumezbeur

this hydrogen-sulfate increasings were associated with the growth of the piger community - Fouad Boumezbeur

study of the genes involved in sulfate reduction and utilization of hydrogen : these genes are required for colonization of mice in both low-fat and high-fat diets - Fouad Boumezbeur

however, diet can play a role as a selective pressure - Fouad Boumezbeur

milk products expose our microbiota to bacterial exposure, resulting in shared community responses to probiotics intake. - Fouad Boumezbeur

probiotics impact on the microbiota was studied in human gut microbiota and defined human gut microbial comminity transplanted in gnotobiotic mice, analysed before and after introducing FMP strains - Fouad Boumezbeur

Many correlation between Microbiota but few causes-effect is established - Julien Tap

Rapid colonization of gut babies bu Microbiota dominated by Actinobacteria - Julien Tap

Proteomic analysis reinforce the interplyay between microbes and the human host - Julien Tap

I stop cover De Vos, no consent from him - Julien Tap

you can still have a look on his publication here : http://1.usa.gov/vBwgDn - Julien Tap

question sessions begin - Julien Tap

"Gut microbial communities viewed through the MetaHIT microscope" by Dusko Ehrlich, MetaHIT coordinator - MetaHIT

"Molecular adaptation of lactobacilli to the gastrointestinal tract" by Michiel Kleerbezem - MetaHIT