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KEZDKRDS:

Mi a kedvence?

What is your favorite pet?Kutyus, cicus, kanri, vagy kszertekns?Mirt nem a blflra, amivel letnk els napjaitl az utolsig egytt lnk s testi-lelki jltnk lettemnyese?1

KRDS 2:

Mi az ami Te vagy

s mgis Nlad tbb?A mikrobiomod (lsd ksbb).2

KRDS 3:

Melyik a (kt) legstupidabb llny a Fldn?A blcsek blcse (H. sapiens sapiens) s legjobb bartja (m azt rontotta meg), mert egyedl ez a kt faj nem tudja, hogy mi a termszetes tpllka. Ha lttl mr kutyt csokoldt enni, ekkor egybl rted.3

Utazs a blflrm krlA faeces apotheosisaFrecskaEde sSzabAttila

201402.26.Bemutatom msodik testi nedet: Lady (vagy Miszter) Kak-t (jobb oldalon).Alcm: A szar dicsrete.4

Bltartalmunk 10-szer annyi sejtet tartalmaz mint szkebb magunk (ami nem mag, inkbb tokja a msiknak). Gntartalma pedig 100-szorosa a minknek.

Kt lbon jr Petri csszk vagyunk!Az elfelejtett szervezetHa exobiolgus lennk az Alfa Centaurirl s nagydoktorim tmja a gndiverzits lenne, akkor rdekldsem nem a gyr genomikj hegedtok jelleg hordozra fkuszlna. Most mr vilgos az UFO elrablsok (alien abduction) clja. Nemde?A humn szuperorganizusEmberi sejtekMikrobita organizmusok(vrus, baci, gomba)A humn genom nem vlaszthat el a mikrobiomtl!A mikrobita szerves rsze fenotpusunknak!Mikrobita genom(mikrobiom)A teljes emberi gnkszletHumn genom6

A humn mikrobita rsze a blflra300-1000, klnbz faj mikroorganizmusKommenzulis, st szimbiotikus kapcsolatban velnk, amely mgtt vmillis koevolci llMinden szinten szinte mindent befolysol a gazdaszervezetben

Bourlioux P et al. 2003, Am J Clin Nutrletre szl albrlink8Klcsns fggsbenA blflra szmos hasznos funkcit lt el:kihasznlatlan kalrikat fermentlgy a pH-t alacsonyan tartjaelnyomja a krokozkataz immunrendszert trenrozzaa bl, s az agy fejldst szablyozzavitaminokat termel (pl. biotin s K vitamin)beleszl a zsrhztartsbaf forrsa a kinurnsavnak s SCFA-nak (blhmsejtek, immunsejtek s neuronok szmra)Toll-like receptorokon keresztl reparlja a beletCarbohydrates that humans cannot digest without bacterial help include certain starches, fiber, oligosaccharides and sugars that the body failed to digest and absorb[2][10][11] like lactose in the case of lactose intolerance and sugar alcohols, mucus produced by the gut, and proteins.[10] A further result is flatulence, specifically due to the metabolism of oligosaccharides (notably from beans) by many different species.

SCFA - short chain fatty acid9

A tau'ri-k szimbitja is gygytja a rkot!Stargate SG-1, 1997

Szimbitnk immunregulcis hatsaicitokin aktivci, nyirokszvet stimulcitolerancia orlis allergnekkel szembenaz immunrendszert diszkrimincira tantjaa T-helper 17 sejtek kizrlag mikrobita hatsra differencildnak s aktivlsuk (pTH17 vlasz) tumor ellenes immun-krnyezetet teremta ciklofoszfamid s a platina kemoterpia hatsa is a mikrobitn keresztl rvnyesl!Viaud S et al. 2013, Science; Iida N et al. 2013, Science11Stargate SG-1, 1997

Szmos kritikus gn expresszijt modulljk: pl. BDNF, NMDAs 5-HT receptorokt.Kmiai ton kommuniklnak a striatummal, hippocampusszal, amygdalval, hypothalamusszal s a cingulummal. A blflra idegrendszeri hatsai

Rgta ismert tny, hogy az intestinlisan steril patknyok stresszrzkenyebbek, szorongbbak s kevesebb explortoros aktivitst mutatnak.A blflra befolysolja a stresszreakcit

A mikrobita-bl-agy tengely

Az agy-immun-bl hromszg (BIG-T) kzpontban a mikrobitval

bl-agy interakcibl-immun interakciagy-immun interakci

Szabo A & Rajnavolgyi E, 2013trend s blflraA blflra hrom f enterotpusa a hrom f tpanyag (sznhidrtok, zsrok s fehrjk) lebontsban kvziszelektvAz trendtl fggen vltozik a entero-tpusok egymshoz viszonytott arnyaKvetkezmnyes vltozsokkal a korbban felsorolt funkcikbanNincs mg olyan szervnk amely ennyire rzkeny lenne letmdvltozsokra!

1. Arumugam M. 2011, Nature; 2. Muegge BD. 2011, Science17An enterotype is a classification of living organisms based on its bacteriological ecosystem in the gut microbiome. The discovery of three human enterotypes was announced in the April 2011 issue of Nature by Peer Bork and his associates. They found that enterotypes are not dictated by age, gender, body weight, or national divisionsTmegpusztt fegyverek

Az alapjaiban elhibzott USDA* piramisTbbek kztt, mert nem termszetes, fejlds-tanilag fiatal dits komponensekre alapoz (gabonaflk, lisztes gumk, s hvelyesek).

Mi ms vrhat egy mezgazdasgi minisztriumtl?!*

* USDA= United States Department of AgricultureTbb szzmilli ember elhzsrt s kvetkezmnyes hallozsrt felelsek megalkoti. Ez nem tartozik a Hgai Brsgra?A nem sokkal klnb Harvard piramis

Csak nem tud elszakadni a teljes kirls gabona mtosztl. A szjt sem hagyja ki.

tmutat az elhzshoz s a cukorbetegsghezAlacsony zsr, limitlt fehrje s magas komplex sznhidrt tartalm trendet kvessEgyl teljes kirls gabont (tnklybzval, vadrizzsel)Igyl gymlcslevet vagy dtitaltKvesd a D vitamin szedsnek jelenlegi elrsaitReggelire fogyassz zabpelyhet vagy gabonamzlitMagas vrnyomsodra szedj vzhajtt vagy btablokkolttrend vltozsok a hominin evolciban rovarevs> 100 milli v levl- s gymlcsevs (lombdita) 18 milli v hs- s zldsgevs (paleolit dita) < 200 ezer v fmag- s gumevs (farmer dita) < 11 ezer v hulladk- s manyagevs (kanap dita) < 100 v

Hominin fejlds genercikban

Carrera-Bastos P et al. 2011, Res Rep Clin Cardrk, szvbaj, cukorbaj, gutats, impotencia, zleti bntalmak, PCO, vrszegnysg, akn, alopcia, allergia, autoimmun betegsgek, fogsorvads, fogtorlds, keskeny orr s arca civilizci bevezetse utn egy-kt genercin bell ezek megjelennek

Ami hinyzott a paleolit letbl

4060 ves gyjtget-vadszok vrnyoms rtkei

Vrnyoms s kor Yanomamo indinoknl [Hgmm]Perzisztl inzulinrzkenysg a kzp- s idskorak krbenAlacsony homi plazma leptin a horti-kultrlis Kitava s a gyjtget-vadsz Ache indinoknl (Paraguay) egszsges svd populcihoz s szak-amerikai hossztvfutkhoz viszonytvaKivl csontintegrits mutatk a fenti populcikbanNhny egszsgi mutat pre-agrikulturlis trsadalmakbanCarrera-Bastos P et al. 2011, Res Rep Clin CardAz agy fejldsnek 4+1 kvetelmnye. Azaz mire kell(ett) a j koszt?Kalriaforrsptkbnyavitaminokesszencilis amino- s zsrsavaknyomelemekBioregulciantioxidnsokflavonoidok, szteroloks zilli fitokemikliaA blflra karbantartsa+1. A puberts ksleltetse

Azok a rgi, szp idk, amikor a mogyornk nagyobb volt az agyunknl!

fullmaturationfullmaturation10-years delaypubertypubertyA korai puberts hatsa az agy nvekedsre2 ves elny 10 v lemaradst okoz!Ez a j koszt hatsa lenne?Szivrg bl: a degeneratv s immunbetegsgek meleggyaA civilizlt bl jellemzje a fokozott permebilits.Az a megfigyels indtotta el, miszerint autisztikus viselkeds javult dits vltoztatsokra.Okai, okozi:a glutn s kazein proteotoxikus hatsa,felborult (diszbiotikus) blflra, stressz, sts, rostszegny tpllkozs, tlzsba vitt fizikai aktivitsAmelynek talajn:a blhmsejtek kapcsoldsa fellazul (szivrg bl)Amit tovbb fokoz:NSAID, aszpirin, szteroid, savcskkent (PPI), antibiotikum

A fokozott tereszt kpessg blen t a keringsbe kerl anyagok az anti-inflammatorikus pro-inflam-matorikus interleukin egyenslyt a pro-inflammatorikus irnyba toljk el, gy a szivrg bl chronic low-grade inflammation-t generalizl a egsz szervezetben.

Kvetkezmnyknt a megnvekedett blpermebilits kiterjed MINDEN membrnra s barrier-re (m. vr-agy gt, synovialis stratum, hrg s td nylkahrtya). A szivrg bl elmlet szerint a kiterjedt hatrzavar felel a civilizcis betegsgek j rszrt.Leaky Gut s a GUT (Grand Unification Theory) a medicinban

A glutnrzkenysg fokozataiLeaky

Alzheimer demencia vezet azon betegsgek sorban, amelyek magasan korrellnak endotoxmival Bengmark S. 2013, Pharmacol ResA szivrg bl szindrma tnetei

34

Szivrg bl szindrmval egyttjr(hat) llapotokAlzheimers dementiaCancerAttention deficitLupusParkinsons diseasePolycystic ovaryChildhood hyperactivityAutism spectrum disordersMacular degenerationDepressionOsteoporosis

35A clearance hipotzis szerint:A vr-agy gt nemcsak gt, hanem egy dinamikus oda-vissza szablyoz fellet (interface) a vr s a KIR kztt1 Az amiloid--peptid (ABP) oldhat formjnak felvtelt s leadst a vr-agy gton keresztl befel receptors for advanced glycation end products (RAGE) s kifel low-density receptor-related protein-1 (LRP1) komplexek szablyozzk2 Az ABP transzportjnak deficitje meghatroz tnyez az amiloid plakkok kialakulsban LPS induklta gyullads az ABP beram- lst nveli s kiramlst cskkenti3 Mindezen fell az endothelilis sejtek krosodsa is kimutathat, amely permeabilitst nvel faktor4

A vr-agy gt zavara Alzheimer krban1. Sharma HS et al. 2012, Int Rev Neurobiol; 2. Deane R et al. 2009, CNS Neurol Disord Drug Targets; 3. Erickson ME et al. 2012 J Neuroinflammation; 4. Bowman GL and Quinn JF 2012, Aging Health36

Az ASD szivrg bl + exorfin hipotzise 1A londoni Royal Free Hospital vizsglata tbb blkrosodst tallt autista gyerekekben (N=60) mint a kontroll csoportban.Az autistk 90%-a krnikus blhurutban szenved.A rosszul emsztett glutnbl s kazeinbl szrmaz gliadomorfinok s kazomorfinok:felszvdsra kerlnektlpnek a vr-agy gtonbta-endorfin-szer hatsokat vltanak ki1. Wakefield AJ. 2000, Am J Gastroenterol; 2. Shattock P. 2002, Expert Opin Ther Targets 37

Per os adott glutn tredkek detektlhatak voltak patkny agyban

Az agy opioid receptorai ktnek gliadomorfint

Parenterlis kazomorfin hatsa kimutathat volt a kzponti idegrendszerbenAz ASD szivrg bl + exorfin hipotzise 21. Dohan FC. 1980, N Engl J Med; 2. Hemmings WA. 1978, Lancet38Curr Opin Psychiatry 2011, 24(6):519-525Inflammatory mechanisms in major depressive disorder.BMC Medicine 2013, 11(200):1-16So depression is an inflammatory disease, but where does the inflammation come from?ditahibaszivrg blstresszelhzsatopiaD vit. hinynysorvadsRaedler TJ.

AbstractAs the monoamine hypothesis of depression' fails to explain all aspects of major depression, additional causes are being investigated. Several observations suggest that inflammatory mechanisms pay a role in the cause of major depressive disorder (MDD). This article reviews their role in major depression.Recent studies support the concept that inflammatory mechanisms play a crucial role in the pathomechanisms of major depression. Major depression shares similarities with 'sickness behavior', a normal response to inflammatory cytokines. Elevations in proinflammatory cytokines and other inflammation-related proteins in major depression were found in plasma and cerebrospinal fluid (CSF) as well as in postmortem studies. Elevated levels of proinflammatory cytokines persist after clinical symptoms of depression are in remission and can also predict the onset of a depressive episode. Antidepressant treatment can lead to a normalization of elevated cytokine levels in major depression. Finally, we understand how inflammatory mechanisms affect the metabolism of tryptophan and how nonsteroidal antiinflammatory drugs (NSAIDs) can interfere with the effects of antidepressants.39Depresszi s gyullads1. Reichenberg A et al. 2001, Arch Gen Psychiatry; 2. Udina M et al. 2012, J Clin Psychiatry; 3. Connor TJ et al. 1998, Life Sci; 4. Xia Z et al. 1996, Immunopharmacology; 5. Maes M et al. 1999, NeuropsychopharmacologyCitokineket stimull endotoxin infzi tipikus major depresszis tneteket okoz egszsgesekben1 Exogn citokinek parenterlis adagolsa a depresszi viselkedses, affektv s kognitv tneteit okozhatja (pl. a hepatitis C interferon kezelse folyamn a pciensek negyede depresszis lesz)2,3Antidepresszvumok, kivltkpp SSRI-ok, cskkentik a pro-inflammatorikus citokinek szintjt: pl. TNF-, IL-1; s nvelik az anti-inflammatorikus citokinekt: pl. IL-104,5SSRI-k a fenti faktorok gnexpresszijt is hasonl irnyba modulljk fehrvrsejtekben40J reggelt! a blflrnakCanopy smoothie 2 szemlyre:1 kis alma hjastul1 kis krte hjastul1 kivi hjastulutna a molnr fazekastul...1/2 bann hjatlanul1 salta levl1 kelkposzta levl1 piroskposzta levl2 knai kel levlnhny spent levl1 fej gomba1 evkaln fahjkevs szerecsendi, szegfszeg meg gymbr pordurr bele csukamj- vagy lenolajmz zestsnek2 deci vz (vagy tea) hgtnakavocado ha van, szz olvaolaj is ptolhatja nmilegSEMMI TEJ, SEMMI SZJA! TOJS OK!41Flavonoids: apples, apricot, cherry, cocoa, cranberries, grapes, hip, kiwi, olives, peach, pears, plum, pomegranate, and strawberries (countless berries and tropical fruits)Carotenoids: basil, beets (NC), carrots (NC), citrus fruits, coriander, dark leafy greens, dill, lovage, mint, parsley, pumpkin, rosemary, sage, and tarragonTurpenes: citrus and spinachAllyl sulfides: garlic (NC but modified leaf), chives, leeks, scallion, ramson, shallots, and onions (NC but modified leaf)Isothiocyanates: cabbage, cauliflower, broccoli, bok choy, brussels sprout, artichoke, asparagus, kale, turnips, mustard greens, and chard (NC)Curcuminoids: turmeric (NC) and ginger (NC)Spices: black pepper, cinnamon, clove, and nutmegFermented food: sauerkraut, chimchi, kombucha, and picklesAnti-inflammatory food cropsNC = not canopy; others yes!42CD4+ - T helperTh0 - naiveTh1Th3TregTh2CellularHumoralTolerantIL-2IL-12INF-IL-4IL-9IL-13IL-10 TGF-T helper-fgg immunvlaszokDott. Salvatore Bardaro - www.amnco.itdepresszi Th2 (humorlis)IL-4, IL-5, IL-9, IL-13 depresszi Th1 (cellulris)IL-2, IL-12, IFN-, TNF- Citokinek depresszibanA blflra diszbizisa Th1 irnyba tolhatja el az egyenslytDaganatIl-1 kritikus kapcsolatban van gyulladssal s onkogenezisselIL-1 a stressz hatsok fontos meditoraStresszDepressziIL-1 adagolsa depresszv tneteket induklIL-1 gtolja a hippocampalis neurogenezistAz IL-1 kapcsolatA diszbiotikus blflra emeli az IL-1 szinteketSaid HS et al. 2013, DNA ResWe can say that the marker of Th2 Inflammation, thats to say the low grade chronic systemic inflammation, is the IL-1Beta.Il1-Beta is recognized as a common element in Cancer, Stress and Depression. .Anedonia: mancanza di piacereInflammation (Th2)CANCER: Il-1 is a critical link between inflammation and oncogenesis IL-1beta, besides its central role in inflammation, is a powerful player in tumour progression, angiogenesis, invasiveness and cell migrationSTRESS: IL-1 is an essential mediator of the effects of stress (IL-1beta is also a critical mediator of the antineurogenic and depressive-like behavior bhevj(r)/caused by chronic stress - Stress decreases neurogenesis in the adult hippocampus)FOETUS: Detectable serum levels of IL-1 are predictive of successful implantation and ongoing pregnancy 45Feher et al. 2011, Orv Hetilap

46StresszDepressziBlfalLizoszma tlterhelsLPS- s endotoxmiaChronic, low-grade inflammationPro-inflammatorikus citokin tlslyIntestinal barrier impairment is incriminated in the pathophysiology of intestinal gut disorders associated with psychiatric comorbidity. Increased intestinal permeability associated with upload of lipopolysaccharides (LPS) translocation induces depressive symptoms. Gut microbiota and probiotics alter behavior and brain neurochemistry. Since Lactobacillus farciminis suppresses stress-induced hyperpermeability, we examined whether (i) L. farciminis affects the HPA axis stress response, (ii) stress induces changes in LPS translocation and central cytokine expression which may be reversed by L. farciminis, (iii) the prevention of "leaky" gut and LPS upload are involved in these effects.Psychoneuroendocrinology. 2012 Apr 25. [Epub ahead of print]Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats.Ait-Belgnaoui A, Durand H, Cartier C, Chaumaz G, Eutamene H, Ferrier L, Houdeau E, Fioramonti J, Bueno L, Theodorou V.SourceNeuro-Gastroentrologie and Nutrition Team, TOXALIM, UMR 1331-INRA/INP/UPS, Toulouse, France; Institut Rosell-Lallemand, Blagnac, France.AbstractBACKGROUND AND AIMS: Intestinal barrier impairment is incriminated in the pathophysiology of intestinal gut disorders associated with psychiatric comorbidity. Increased intestinal permeability associated with upload of lipopolysaccharides (LPS) translocation induces depressive symptoms. Gut microbiota and probiotics alter behavior and brain neurochemistry. Since Lactobacillus farciminis suppresses stress-induced hyperpermeability, we examined whether (i) L. farciminis affects the HPA axis stress response, (ii) stress induces changes in LPS translocation and central cytokine expression which may be reversed by L. farciminis, (iii) the prevention of "leaky" gut and LPS upload are involved in these effects.METHODS: At the end of the following treatments female rats were submitted to a partial restraint stress (PRS) or sham-PRS: (i) oral administration of L. farciminis during 2 weeks, (ii) intraperitoneal administration of ML-7 (a specific myosin light chain kinase inhibitor), (iii) antibiotic administration in drinking water during 12 days. After PRS or sham-PRS session, we evaluated LPS levels in portal blood, plasma corticosterone and adrenocorticotropic hormone (ACTH) levels, hypothalamic corticotropin releasing factor (CRF) and pro-inflammatory cytokine mRNA expression, and colonic paracellular permeability (CPP).RESULTS: PRS increased plasma ACTH and corticosterone; hypothalamic CRF and pro-inflammatory cytokine expression; CPP and portal blood concentration of LPS. L. farciminis and ML-7 suppressed stress-induced hyperpermeability, endotoxemia and prevented HPA axis stress response and neuroinflammation. Antibiotic reduction of luminal LPS concentration prevented HPA axis stress response and increased hypothalamic expression of pro-inflammatory cytokines.CONCLUSION: The attenuation of the HPA axis response to stress by L. farciminis depends upon the prevention of intestinal barrier impairment and decrease of circulating LPS levels.47Most azon muszj elmerengnem:hogyha te nem lennl velem,elvesztenm dolgos belem,s kimerlne fradt lelkem. BlflrnakA Nyjas HallgatnakTMOGASD A MIKROBITT!Sok embernek nincs ms kultrja48Chart16564.57069.57574.58079.58584.59089.59590.59691.59792.59893.59994.599.895.510096.510097.510098.510099.310099.8

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