{"id":25810,"date":"2022-12-28T12:19:32","date_gmt":"2022-12-28T11:19:32","guid":{"rendered":"https:\/\/www.mylav.net\/nekategorizirano-sl\/microbiote-et-microbiome-intestinaux-ce-que-cest-et-comment-les-utiliser-clinique\/"},"modified":"2024-02-07T12:45:01","modified_gmt":"2024-02-07T11:45:01","slug":"crevesna-mikrobiota-in-crevesni-mikrobiom-za-kaj-gre-in-kako-ju-lahko-uporabimo-v-klinicni-praksi","status":"publish","type":"post","link":"https:\/\/www.mylav.net\/hr\/nekategorizirano-sl\/crevesna-mikrobiota-in-crevesni-mikrobiom-za-kaj-gre-in-kako-ju-lahko-uporabimo-v-klinicni-praksi\/","title":{"rendered":"\u010cREVESNA MIKROBIOTA IN \u010cREVESNI MIKROBIOM ZA KAJ GRE IN KAKO JU LAHKO UPORABIMO V KLINI\u010cNI PRAKSI"},"content":{"rendered":"<p>Vse pogosteje je govora o mikrobiomu in mikrobioti, tako v humani medicini kot tudi na na\u0161em veterinarskem podro\u010dju; o \u010dem je govora in kak\u0161en mo\u017een razvoj lahko pri\u010dakujemo v prihodnosti?<\/p>\n<p>O tem bomo spregovorili v novem blogu, ki je sad sodelovanja dveh strokovnjakov laboratorija Mylav: dr. Bottera in dr. Ruggiera.<\/p>\n<p>Prebavni trakt je dom zapletenemu ekosistemu, sestavljenemu iz razli\u010dnih skupnosti mikroorganizmov (bakterij, glivic, virusov, arhej in protozojev), imenovanem <strong>mikrobiota<\/strong>; z izrazom mikrobiom pa ozna\u010dujemo kompleksen sklop izra\u017eanja (ekspresije) genov teh mikroorganizmov.<\/p>\n<p>Glavnino mikrobiote predstavljajo bakterije (pribli\u017eno 97-99 %), ki se delijo na fakultativne in obligatorne anaerobe in so razporejene po celotnem prebavnem traktu.<\/p>\n<p>Prevladuje pet vrst bakterij (phyla): <strong>Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria in Actinobacteria<\/strong> (Honnefer 2017).<\/p>\n<p>V <strong>\u017eelodcu<\/strong> pri psu je prisotnih le nekaj vrst bakterij, ki so odporne na kislo okolje; med njimi so Helicobacter in v manj\u0161i meri laktobacili; <strong>tanko \u010drevo<\/strong> naseljujejo aerobne ali pogojno (fakultativno) anaerobne bakterije (Proteobacteri), medtem ko v <strong>debelem \u010drevesu<\/strong> prevladujejo obligatorno anaerobne bakterije (Clostridia, Bacteroides, Fusobacterium).<\/p>\n<p>Sestava mikrobioma slehernega posameznika je edinstvena in svojevrstna, \u010deprav obstajajo \u0161tevilne podobnosti med ljudmi in \u017eivalmi, ki \u017eivijo v podobnih epidemiolo\u0161kih razmerah.<\/p>\n<p>Kljub tem filogenetskim razlikam so si <strong>kon\u010dni metabolni produkti<\/strong> mikrobioma v prebavnem traktu posameznikov med seboj podobni. (Handl 2011).<\/p>\n<figure id=\"attachment_25793\" aria-describedby=\"caption-attachment-25793\" style=\"width: 900px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.mylav.net\/wp-content\/uploads\/2022\/12\/blog_microbiota_microbioma_fr.png\" alt=\"Taksonomska porazdelitev petih najbolj zastopanih debel v vzorcu blata pri psu (fotografija: dr. Michele Marino)\" width=\"900\" height=\"636\" class=\"size-full wp-image-25793\" \/><figcaption id=\"caption-attachment-25793\" class=\"wp-caption-text\">Taksonomska porazdelitev petih najbolj zastopanih debel v vzorcu blata pri psu (fotografija: dr. Michele Marino)<\/figcaption><\/figure>\n<p>Sodelovanje \u010drevesne mikrobiote z njenim gostiteljem je dvosmerno, dinami\u010dno in spremenljivo v skladu z modelom vzajemne simbioze, tj. mutualizma, pri katerem imata obe komponenti (\u017eivalska in mikrobna) koristi v smislu dobrega po\u010dutja in pre\u017eivetja. V vseh pogledih je to <strong>dejanski organ<\/strong>, ki je v interakciji predvsem, vendar ne izklju\u010dno s prebavnim sistemom (Baquero 2012).<\/p>\n<p>Veliko \u0161tevilo genov, ugotovljenih v mikrobiomu (pribli\u017eno 3,3 milijona) predstavlja spremenljivo genetsko zasnovo psa ali \u010dloveka; zaradi njegove izjemne sposobnosti prilagajanja evolucijskim potrebam, ki se spreminjajo skozi \u010das, so ga poimenovali &#8220;<strong>adaptom<\/strong>&#8220;.  Po mnenju \u0161tevilnih avtorjev je bil ta &#8220;adaptom&#8221; temeljnega pomena za evolucijo ljudi in \u017eivali in odigrava klju\u010dno vlogo v zapletenem svetu epigenetike.  <\/p>\n<p>Trenutno \u0161e vedno ni mogo\u010de opredeliti, kdaj je mikrobiom &#8220;normalen&#8221;, saj ima vsak posameznik zelo individualen nabor mikroorganizmov, ki ga pridobi z rojstvom in ki se ohranja vse \u017eivljenje in se spreminja zaradi fiziolo\u0161kih, parafiziolo\u0161kih in patolo\u0161kih dogodkov, kot so staranje, spremembe v prehrani in bolezni. Kolonizacija na povr\u0161inah sluznice in ko\u017ee otroka se pojavi \u017ee ob rojstvu in se spreminja glede na na\u010din samega poroda (carski rez, naravni porod) in na okoljske dejavnike (dom, dru\u017eina in hi\u0161ne \u017eivali).<\/p>\n<p>Pomembni prelomi v \u017eivljenju so klju\u010dnega pomena tako za gostitelja kot za mikrobioto. Tako na primer pri odstavljanju pasjega mladi\u010da postopen prehod z mle\u010dne prehrane na trdno hrano spodbudi izrazit porast <strong>Bacteroidetes<\/strong> (od 1 % v dveh dneh do 39 % v dveh mesecih), ki razgrajujejo polisaharide, ter <strong>Fusobacteria<\/strong>, ki fermentirajo beljakovine in aminokisline in proizvajajo kratko veri\u017ene ma\u0161\u010dobne kisline (Small Chains Fatty Acids &#8211; SCFA).<\/p>\n<p>Pestrost vrst mikroorganizmov (biotska raznovrstnost) v blatu pasjih mladi\u010dev se znatno pove\u010da od starosti 2 dni do 52 tednov (Guard 2017), medtem ko so pri psih, starih od 3 mesecev do 12 let, opazili le malo ali ni\u010d sprememb v mikrobni raznolikosti (You 2021); to bi lahko podobno kot pri ljudeh nakazovalo, da se biotska raznovrstnost mikrobiote mladi\u010dev v poporodnem obdobju pove\u010da, nekaj mesecev po odstavitvi stabilizira, nato pa pri nara\u0161\u010dajo\u010di starosti po\u010dasi upada.<\/p>\n<p>Ta strnjen \u010dasovni prikaz poudarja pomen neonatalnega in mladostnega obdobja za oblikovanje mikrobioma, ki bo biotsko raznovrsten in kompleksen. Bazalna mikrobiota, ki se po mnenju \u0161tevilnih strokovnjakov oblikuje v prvih 4-6 mesecih \u017eivljenja psa, se imenuje &#8220;jedrni&#8221; mikrobiom.  Ravno v tej fazi lahko vse, kar pes izkusi, zau\u017eije ali preboli, v veliki meri vpliva na to, kako zdrav ali ob\u010dutljiv bo v prihodnosti.<br \/>\nLastnikom, vzrediteljem in veterinarjem je treba pojasniti, kako pomembno je v tej fazi podpirati in obvarovati mikrobiom. Nasprotno pa gre pri upadu raznolikosti \u010drevesne mikrobiote s staranjem za povsem fiziolo\u0161ki dogodek (Mizukami 2019).<\/p>\n<p>Poudariti je treba tudi, da je vez med prehrano in mikrobioto osrednjega pomena skozi celoten \u017eivljenjski ciklus. Tako je na primer mikrobiota klju\u010dna za vzpostavitev tako imenovane &#8220;oralne tolerance&#8221;, ki vpliva na bolnikovo dovzetnost na imunske motnje, kot so atopija ali kroni\u010dne vnetne enteropatije.<\/p>\n<p>Kot vsak drug organ ima tudi mikrobiota \u0161tevilne in zelo raznolike <strong>vloge<\/strong> in funkcije ter interakcije na \u0161tevilnih podro\u010djih: <strong>presnovno<\/strong> (npr. pretvorba \u017eol\u010dnih kislin), <strong>obrambno<\/strong> (npr. premagovanje in odpornost na patogene, kar predstavlja klju\u010dno sestavino naravne \u010drevesne pregrade), <strong>trofi\u010dno<\/strong> (npr. sinteza vitaminov B in K, proizvodnja SCFA), <strong>imunolo\u0161ko<\/strong> (npr. oralna toleranca) in <strong>nevroendokrino<\/strong> (npr. GABA, uravnavanje \u010drevesne peristaltike in izlo\u010danja).   <\/p>\n<p>Za <strong>kakovostno<\/strong> oceno mikrobiote je treba poznati koncept evbioze in disbioze.<\/p>\n<p>Z evbiozo je mi\u0161ljeno kakovostno in koli\u010dinsko ugodno ravnovesje sestavin mikrobioma, ki omogo\u010da pozitivno presnovno in imunolo\u0161ko sodelovanje z gostiteljem, izbolj\u0161uje delovanje prebavnega trakta, optimizira vnos hranil, uravnava imunsko odzivnost ter vnetne procese v \u010drevesju in sistemu nasploh.<\/p>\n<p><strong>Disbioza<\/strong> pa pomeni strukturno spremembo mikrobioma, tako v smislu sestave kot tudi delovanja (prese\u017eek patobiontov, zmanj\u0161anje ali celotna izguba &#8220;dobrih&#8221; komenzalnih bakterij, selektivna izguba nekaterih specifi\u010dnih sevov, sprememba profila mikrobiote, pritrjene na sluznico itd.).<\/p>\n<p>Pomembno je poudariti, da ti pojmi nimajo ostro za\u010drtanih in prekrivajo\u010dih se meja med posamezniki, ki pripadajo razli\u010dnim vrstam in\/ali razli\u010dnimi posamezniki iste vrste. Prag sprememb, po katerem lahko govorimo o disbiozi, se spreminja, prav tako pa \u0161e ni nedvoumno dogovorjeno, kateri je idealen, torej evbioti\u010den nabor bakterij, na podlagi katerega bi lahko opredelili tudi njegove spremembe.<br \/>\nNagnjenost k razvoju \u010drevesne disbioze je odvisna od zna\u010dilnosti in stabilnosti &#8220;jedrnega mikrobioma&#8221;, pri \u010demer je treba poudariti, da ima slednji veliko sposobnost obnavljanja svoje prvotne sestave (t.i. <strong>rezilienca<\/strong>) po tem, ko je bil izpostavljen mote\u010demu dogodku.<\/p>\n<p>Kako lahko torej opi\u0161emo in ocenimo stanje mikrobioma? Medtem ko so za ve\u010dino trebu\u0161nih organov na voljo klini\u010dno-patolo\u0161ke analize in metode posredne slikovne diagnostike, se pri analizi mikrobioma zana\u0161amo na tako imenovane &#8220;omi\u010dne znanosti&#8221; (metagenomika, metabolomika, proteomika in transkriptomika), ki temeljijo na na\u010delih napredne bioinformatike in kompleksnih analiti\u010dnih orodjih, ki so bili \u0161e pred nekaj leti nedostopna.  <\/p>\n<p><strong>Metagenomska analiza<\/strong> temelji na preu\u010devanju niza zaporedij DNK iz razli\u010dnih mikroorganizmov.<\/p>\n<p>Tehnologija <strong>sekvenciranja naslednje generacije<\/strong> omogo\u010da identifikacijo \u010drevesnih mikrobiolo\u0161kih skupnosti z analizo variabilnih regij V2-V4-V8 e V3-V6\/7-V9 gena, ki kodira RNA 16S; ker je prisoten v vsaki bakteriji, ga je namre\u010d mogo\u010de uporabiti kot merilo za razvr\u0161\u010danje. Seveda pa lahko na rezultate vpliva ve\u010d predanaliti\u010dnih dejavnikov (zbiranje matric, ekstrakcija RNA, primerji, uporabljena tehnologija). \u010ce povzamemo, za sekvenciranje gena 16S rRNA mikrobioma ne obstaja en sam, najbolj\u0161i pristop, vendar bi lahko razumevanje nekaterih njegovih omejitev, doslednost metod analize in uporaba dopolnilnih tehnik (NGS, qPCR, metabolomika) pomagali odpraviti vsaj nekatere od \u0161tevilnih dvomov.<\/p>\n<p>Zaradi \u0161tevilnih in raznovrstnih vlog, ki jih ima \u010drevesni mikrobiom pri fiziolo\u0161kih in patolo\u0161kih stanjih, pomen njegove analize ni zgolj \u0161pekulativne narave, temve\u010d predstavlja dejansko razse\u017enost s terapevtskega vidika.<\/p>\n<p>Tako imenovana &#8220;<strong>modulacija mikrobiote<\/strong>&#8221; se v praksi \u017ee uveljavlja, \u010deprav na nekoliko okoren in empiri\u010den na\u010din, z uporabo probiotikov, prebiotikov, simbiotikov, antibiotikov in fekalne transplantacije.<\/p>\n<p>Farmacevtska industrija \u017ee vrsto let uvr\u0161\u010da t.i. &#8220;bioprotiko&#8221; in modulacijo mikrobioma v ospredje svojih raziskav, katerih cilj je opredeliti terapevtska orodja, ki lahko popravijo specifi\u010dne vzorce disbioze, povezane z razli\u010dnimi vrstami bolnikov in bolezni. Po vsej verjetnosti smo na pragu nove dobe v zdravljenju gastroenterolo\u0161kih bolnikov.<\/p>\n<div class=\"riferimenti\">\n<h5>Literatura:<\/h5>\n<p>Jan Suchodolski, Jennifer Camacho, J\u00f6rg M. Steiner, Analysis of bacterial diversity in the canine duodenum, jejunum, ileum, and colon by comparative 16S rRNA gene analysis, FEMS Microbiology Ecology, Volume 66, Issue 3, December 2008<\/p>\n<p>Honneffer, J.B., Steiner, J.M., Lidbury, J.A. et al. Variation of the microbiota and metabolome along the canine gastrointestinal tract. Metabolomics 13, 26 2017.<\/p>\n<p>Guard BC, Mila H, Steiner JM, Mariani C, Suchodolski JS, Chastant-Maillard S. Characterization of the fecal microbiome during neonatal and early pediatric development in puppies. PLoS ONE. (2017)<\/p>\n<p>You I., Kim M.J. Comparison of Gut Microbiota of 96 Healthy Dogs by Individual Traits: Breed, Age, and Body Condition Score. Animals 2021, 11, 2432.<\/p>\n<p>Mizukami K, Uchiyama J, Igarashi H, Murakami H, Osumi T, Shima A, et al. Age-related analysis of the gut microbiome in a purebred dog colony. FEMS Microbiol Lett. (2019)<\/p>\n<p>Pilla R., Suchodolsky J.S. The Gut Microbiome of Dogs and Cats, and the Influence of Diet  Vet Clin Small Anim 51 (2021) 605-621<\/p>\n<p>Garrigues Q, Apper E, Chastant S and Mila H (2022) Gut microbiota development in the growing dog: A dynamic process influenced by maternal, environmental and host factors. Front. vet. Sci. 9:964649.<\/p>\n<p>Pilla R and Suchodolski JS (2020) The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease. Front. vet. Sci. 6:498<\/p>\n<p>Kalenyak K, Isaiah A, Heilmann RM, Suchodolski JS, Burgener IA. Comparison of the intestinal mucosal microbiota in dogs diagnosed with idiopathic inflammatory bowel disease and dogs with food-responsive diarrhea before and after treatment. FEMS Microbiol Ecol. (2018)<\/p>\n<p><strong>Enrico Bottero<\/strong>, dr. vet., strokovnjak za gastroenterologijo Mylav<br \/>\n<strong>Pietro Ruggiero<\/strong>, dr. vet., strokovnjak za gastroenterologijo Mylav<br \/>\n<strong>Michele Marino<\/strong>, mol. biol., odgovoren za oddelek molekularne biologije in genetike Mylav<br \/>\n<strong>Walter Bertazzolo<\/strong>, dr. vet. EBVS &#8211; Evropski specialist za veterinarsko klini\u010dno patologijo (dipl. ECVCP); Znanstveni direktor MYLAV\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Vse pogosteje je govora o mikrobiomu in mikrobioti, tako v humani medicini kot tudi na [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[],"tags":[],"class_list":["post-25810","post","type-post","status-publish","format-standard","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>\u010cREVESNA MIKROBIOTA IN \u010cREVESNI MIKROBIOM ZA KAJ GRE IN KAKO JU LAHKO UPORABIMO V KLINI\u010cNI PRAKSI - MyLav<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.mylav.net\/hr\/nekategorizirano-sl\/crevesna-mikrobiota-in-crevesni-mikrobiom-za-kaj-gre-in-kako-ju-lahko-uporabimo-v-klinicni-praksi\/\" \/>\n<meta property=\"og:locale\" content=\"hr_HR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"\u010cREVESNA MIKROBIOTA IN \u010cREVESNI MIKROBIOM ZA KAJ GRE IN KAKO JU LAHKO UPORABIMO V KLINI\u010cNI PRAKSI - 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