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Hoeveel siektes kan gekoppel word aan ontwrigting in die mikrobioom van 'n mens?

Hoeveel siektes kan gekoppel word aan ontwrigting in die mikrobioom van 'n mens?


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Ek het na die radio geluister en gehoor onlangse navorsing het 'n verband gevind tussen kinders en hoër gevalle van asma wanneer sekere bakterieë in die mikrobioom ontbreek. Hoeveel ander siektes kan aan 'n ontwrigte mikrobioom gekoppel word en is daar maniere om ontbrekende bakterieë te herbevolk?


Dit is 'n oop vraag en 'n aktiewe navorsingsgebied. Jy sal nie 'n definitiewe antwoord op jou vraag van getal kan kry nie, aangesien elke nuwe ontdekking by die totaal sal bydra.

Wat herbevolking betref, ons het nie eers al die stamme van mikrobes wat ons bevolk bepaal nie, baie is baie moeilik om in vitro te kweek, en ons weet nie van al die funksies vir elke spesie nie, so ons het nie 'n duidelike prentjie van wat daar moet wees, watter nie, en of sommige spesies saamwerk om ons 'n voordeel te bied. Vir sekere toestande soos prikkelbare derm-sindroom, is fekale oorplanting een van die behandelings wat beproef is.

Doen 'n literatuursoektog vir onlangse resensies. Nature Resensies is geneig om gedetailleerde resensies te doen, veral oor onderwerpe soos in die nuus soos die Menslike Mikrobioom. Dit is waarskynlik die beste eerste plek om te begin. Dan kan jy begin om na die verwysingsvraestelle wat in die resensie aangehaal word, deur te gaan. Dit sal jou oor die algemeen 'n goeie stand van spel in die veld gee.


Mikrobes in ons en hul rol in menslike gesondheid en siektes

Finale uitkomste van die mees omvattende ontleding tot dusver van mense en hul mikrobiome verbind mikrobes en mikrobiese aktiwiteite definitief met gesondheidsprobleme.

Daar is 'n magtige maar onsigbare koninkryk van mikrobes teenwoordig in jou liggaam. Klein dog ongelooflik kragtig, hierdie duisende spesies en triljoene inwoners woon in alle dele van jou liggaam en vorm die diverse menslike mikrobioom. Hierdie mikrobiome ondersteun en handhaaf jou gesondheid, maar is ook, wanneer die mikrobioom op een of ander manier versteur word, gekoppel aan honderde kwale soos kankers, en outo-immuun- en kardiovaskulêre siektes.

Dit is dus nie verbasend dat die menslike mikrobioom 'n belangrike weg van gesondheidsnavorsing is nie. Dit is een met deurslaggewende implikasies vir ons gesondheid, soos 'n rits onlangs gepubliseerde artikels in Natuur van fase twee van die Menslike Mikrobioomprojek stel voor.

Wie is daar? Opname van die mikrobioom by mense

Die Nasionale Instituut van Gesondheid (NIH) se Gemeenskaplike Fonds het die dekade lange Menslike Mikrobioomprojek (HMP) in 2007 gestig. Die HMP-projek is ontwerp om 'n gemeenskapshulpbron te wees om navorsing te bevorder, in wat destyds 'n jong veld was. Die hoofdoel was om 'n gereedskapkas met datastelle en analitiese en kliniese protokolle te skep vir die groter navorsingsgemeenskap om die mikrobioom in spesifieke siektes en populasies te kan bestudeer.

Die eerste fase van die projek het 'n verwysingsdatastel van die tipes mikrobes (insluitend bakterieë, swamme en virusse) gekatalogiseer wat met vyf spesifieke liggaamstreke geassosieer word: vel, mondholte, lugweë, spysverteringskanaal en urogenitale kanaal, met behulp van monsters wat van 300 gesonde volwasse mans en vroue.

Hulle het DNA-volgordebepalingstegnologieë gebruik wat aangepas is van dié wat eers tydens die Menslike Genoomprojek ontwikkel is om hierdie mikrobiese gemeenskappe te ontleed. Mikrobioomverwante siektes is gewoonlik nie aansteeklik nie, maar het 'n verhouding wat deur die menslike mikrobioom verklaar kan word.

Navorsers het die verwysingsdatastel as 'n padkaart gebruik om die soorte mikrobiese gemeenskapsverskille te identifiseer wat met sulke nie-aansteeklike siektes of toestande geassosieer kan word.

Hier is 'n belangrike waarskuwing.

Navorsers weet nog nie of 'n verandering in 'n mikrobiese gemeenskap tot 'n siekte lei of as 'n mikrobiese gemeenskap verander in reaksie op die ontwikkeling van 'n siekte nie.

Navorsers weet nog nie of 'n verandering in 'n mikrobiese gemeenskap tot 'n siekte lei of as 'n mikrobiese gemeenskap verander in reaksie op die ontwikkeling van 'n siekte nie.

Alhoewel 'n momentopname van die mikrobioommetings in hierdie vroeëre HMP-studies geneem is, was 'n begrip van hoe hierdie gemeenskappe oor tyd verander nodig as hierdie soort studies kon begin om die oorsaak-en-gevolg-verwantskappe van die mikrobioom met siekte te bepaal. Dit is veral belangrik omdat mikrobiese populasies in die menslike liggaam oor 'n mens se leeftyd verander en deur dieet, stres en ander omgewingsfaktore beïnvloed word.

Die navorsers sal in werklikheid 'n video van die mikrobioom en die menslike liggaam moet maak.

Wat doen hulle? Hoe mense en mikrobes interaksie het

Die NIH Common Fund het 'n tweede fase, die Integrative Human Microbiome Project (iHMP) in 2014 begin. Hierdie fase is ontwerp om die metodes te ontwikkel vir die meting en ontleding van biomolekules soos RNA, proteïene en metabolisme-gekoppelde stowwe genoem metaboliete van die mikrobioom en die menslike gasheer.

Die navorsers het hierdie metodes toegepas om drie model-mikrobioom-geassosieerde toestande te bestudeer: premature geboorte, inflammatoriese dermsiekte (IBD) en prediabetes. Die doel was om te evalueer watter biologiese eienskappe of reeks eienskappe bewys is as die nuttigste om insig in hierdie toestande te verkry.

Die navorsers het die mikrobioom van gesonde en aangetaste individue vir elk van die toestande oor 'n lang tydperk bestudeer.

“Ons het 'n inventaris van die mikrobiese spesies in die menslike liggaam voltooi. Maar mikrobes is in wisselwerking met mekaar en met die gasheer. Elkeen kan die ander beïnvloed,” het Lita Proctor, programdirekteur van die Human Microbiome Project, gesê. "Dit was dus belangrik dat ons hierdie tydsensitiewe interaksies tussen die mikrobioom en die gasheer vasgelê het."

Premature geboorte en ontbrekende bakterieë in die vaginale mikrobioom

Premature geboorte, 'n toestand waar vroue geboorte skenk voor 37 weke van swangerskap, is die tweede mees algemene oorsaak van neonatale dood wêreldwyd. Premature geboorte gevalle verskil ook aansienlik volgens bevolking. Volgens die Centers for Disease Control and Prevention, in 2016, was die koers van voortydige geboorte onder Afro-Amerikaanse vroue 14% in vergelyking met wit vroue op 9% - 'n byna 50% verskil.

Omdat 'n swanger vrou se gesonde vaginale mikrobioom nou geassosieer word met die gesonde geboorte van 'n baba, het die iHMP se eerste modelstelsel, die Vaginal Microbiome Consortium Multi-Omic Microbiome Study: Pregnancy Initiative (MOMS-PI), gepoog om die vaginale mikrobiome van swangerskap te karakteriseer. vroue om hul risiko vir premature geboorte te meet, met 'n besondere fokus op Afro-Amerikaanse vroue.

Die projek het 'n groep swanger vroue ingeskryf en gevolg wat 'n totaal van 45 premature geboortes en 90 voltermyngeboortes ingesluit het. Deur te kyk na mikrobioomdata, sowel as ander kenmerke, insluitend geenuitdrukking, proteïen- en metabolietvlakke van beide die mikrobioom en die proefpersone, het die navorsers op iets verbasends afgekom.

In een studieresultaat het navorsers die normale vordering van die vaginale mikrobiome in ongekompliseerde swangerskappe vergelyk met dié by vroue wat voortydige geboortes gee. Hulle het bevind dat vroue (meestal Afro-Amerikaanse) wat voortydige geboorte ervaar het, gedurende die vroeë stadiums van swangerskap aansienlik laer vlakke van 'n natuurlik voorkomende bakterie gehad het, Lactobacillus crispatus. Dit is 'n sleutellid van die mikrobioom wat bekend is dat dit belangrik is vir die handhawing van 'n gesonde vaginale omgewing.

Teen die einde van die eerste trimester was die vaginale mikrobiome van hierdie vroue egter geneig om na normaal terug te keer, Lactobacillus-gedomineerde gemeenskap. Die navorsers wil nou weet hoekom hierdie mikrobe in die vroegste dae van haar swangerskap effektief uit die ma se vagina verdwyn.

Hierdie resultaat het ook aan die navorsers bevestig dat die bestudering van die mikrobiese gemeenskapsamestelling van 'n vrou vroeg in swangerskap, en nie later nie, die nuttigste kan wees om risiko vir premature geboorte te voorspel.

Die bestudering van die mikrobiese gemeenskapsamestelling van 'n vrou vroeg in swangerskap, en nie later nie, kan die nuttigste wees om risiko vir premature geboorte te voorspel.

"Hierdie resultate was besonder verblydend en aanvanklik onverwags, omdat hulle vir ons voorstel dat biomerkers vir premature geboorte makliker vroeg in swangerskap opgespoor kan word," sê Gregory Buck, Ph.D., senior ondersoeker van die studie en professor aan Virginia Commonwealth University . "Ons voorspellende model het sensitiwiteit en spesifisiteit reeds effens beter as wat tans gebruik word kliniese parameters."

As hierdie resultate in ander kliniese proewe met Afro-Amerikaanse vroue herhaal word, kan hulle dokters voorsien van mikrobioom-gebaseerde biologiese merkers wat vroeggeboortes vroeg in 'n vrou se swangerskap kan voorspel, en so meer tyd en geleentheid bied vir intervensies om premature geboorte te voorkom.

Inflammatoriese dermsiekte en die verlies van spesifieke mikrobiese produkte

Die sogenaamde "Westerse dieet," gewoonlik gekenmerk as 'n hoë vet, lae vesel dieet, en gereelde gebruik van antibiotika is geassosieer met verskuiwings in die samestelling van die derm mikrobioom van 'n gesonde een. Hierdie verskuiwings is op hul beurt nou geassosieer met verhoogde voorkoms van inflammatoriese dermsiekte (IBD) en die IBD subtipes Crohn se siekte en ulseratiewe kolitis. Albei is pynlike toestande, gekenmerk deur koors, verlies aan eetlus en moegheid, en raak meer as 3 miljoen mense in die VSA.

Daar was min kennis oor die rol van die mikrobioom in IBD en hoe die mikrobioom die vordering van die siekte beïnvloed. Tot nou toe.

Curtis Huttenhower, Ph.D., by die Harvard Skool vir Openbare Gesondheid, Ramnik Xavier, MD, by die Massachusetts General Hospital en ander lede van die iHMP se tweede modelstelsel, die Inflammatory Bowel Disease Multi-omics (IBDMBD)-projek, het die mees omvattende beskrywing van die mikrobiese gemeenskap in IBD.

Hulle het Crohn se siekte en ulseratiewe kolitis pasiënte gewerf wat óf lae vlak inflammasie getoon het óf ten volle ontwikkel het. Eenhonderd-twee-en-dertig pasiënte is vir 'n jaar bestudeer, en vir elkeen het navorsers aan die begin van die studie dermbiopsies geneem, stoelgangmonsters elke twee weke ingesamel en elke vier maande bloedmonsters van hierdie vakke geneem.

Soortgelyk aan die premature studie het navorsers hierdie monsters ontleed vir mikrobioomsamestelling sowel as proteïene, metaboliete en ander biologiese eienskappe. Met daardie data kon navorsers die wisselwerking van die mikrobioom en siektetoestand oor tyd bestudeer.

In baie gevalle het die mikrobioom van IBD-pasiënte in die loop van 'n paar weke heeltemal verander in make-up. Hierdie soort dramatiese verandering was skaars by die nie-IBD-deelnemers.

In baie gevalle het die mikrobioom van IBD-pasiënte in die loop van 'n paar weke heeltemal verander in make-up.

Hierdie navorsers het bevind dat mikrobes wat algemeen in 'n groot oorvloed in gesonde dermmikrobiome voorkom, soos F. prausnitzii en R. hominis, is verminder in die IBD-pasiënte. E coli, 'n ander bakterie wat ook algemeen in gesonde dermmikrobiome voorkom, maar gewoonlik in baie lae vlakke teenwoordig is, het toegeneem in die IBD-pasiënte.

Bakterieë in ons ingewande is noodsaaklik vir die afbreek van ons dieet. Tydens hierdie afbreking produseer bakterieë verbindings, waarvan baie as kommunikasieseine tussen die mikrobioom en die menslike gasheer dien. Die verlies van hierdie bakterieë kan dus hierdie belangrike seinmolekules verminder.

Hierdie studie het 'n beduidende afname in dermbutyraatvlakke gevind, 'n seinmolekule wat deur dermbakterieë gemaak word wat inflammasie verminder en die dermvoering versterk. Die navorsers veronderstel dat die afname in butiraat te wyte kan wees aan die noemenswaardige afname in mikrobes soos bv. F. prausnitzii en R. hominis, wat die belangrikste butyraatprodusente in die dermmikrobioom kan wees.

"Elke individu se mikrobioom en immuunstelsel het duidelik op 'n duidelike, gekoördineerde manier gereageer. Alhoewel dit die komplekse onderlinge verwantskappe wat tot siekte lei moeiliker uitmekaar maak, wys dit ons op nuwe geleenthede om hierdie ongewenste terugvoerlusse moontlik te ontwrig, wat lei tot nuwe maniere om IBD te behandel of te bestuur," het Huttenhower gesê.

Voorkomende staking: Tipe 2-diabetes in sy vroeë stadium

Tipe 2-diabetes (T2D) nader epiese proporsies in die wêreld en is nou gekoppel aan die stygende epidemie van vetsug. Tien persent van die Amerikaanse volwasse bevolking het T2D, en nog 30% is prediabeties. Prediabetes is 'n gesondheidstoestand waar 'n persoon se bloedsuikervlakke verhoog is, maar nie hoog genoeg is om 'n T2D-diagnose te regverdig nie. Dit gebeur omdat beide prediabetiese en T2D-individue gewoonlik aan insulienweerstand ly, waar die liggaam nie meer reageer op die hormoon se seine om glukose uit die bloedstroom na selle te beweeg nie. Byna 70% van die prediabetiese bevolking sal in hul leeftyd diabeet word.

Die iHMP se derde modelstelsel, die Integrated Personal -Omics Project (IPOP), gelei deur Michael Snyder, Ph.D., Stanford Universiteit, en George Weinstock, Ph.D., Jackson Laboratory for Genomic Medicine, is gevorm om fundamentele vrae te beantwoord soos: wat veroorsaak die vordering van prediabetes na T2D? Watter stressors tydens die prediabetes-toestand verhoog die risiko van so 'n verskuiwing?

Die IPOP-studie het 106 gesonde en prediabetiese individue gewerf, wat oor 'n tydperk van vier jaar bestudeer is. Hul derm- en nasale mikrobiome, sowel as biologiese faktore van beide gasheer en mikrobiome is oor daardie vier jaar gevolg.

Om mee te begin, het navorsers bevind dat gesonde deelnemers 'n ander dermmikrobioomsamestelling het as dié met prediabetiese simptome, en sodoende reeds hierdie prediabetiese pasiënte met 'n moontlik verminderde of ongesonde mikrobioom opgestel.

Verder het 'n subset van die gesonde en prediabetiese individue periodes van respiratoriese virale infeksie ervaar, waartydens navorsers hulle albei met die griep-entstof geïmmuniseer het.

Gewoonlik wanneer 'n persoon respiratoriese virale infeksies het, word hul immuunstelsel geaktiveer om die infeksie te beveg. Interessant genoeg, die studie het bevind dat wanneer prediabetiese deelnemers met respiratoriese virale infeksie geïmmuniseer is, hul immuunstelsel stadig was om te reageer, in vergelyking met gesonde deelnemers, maar steeds doeltreffend. Aangesien tipe 2-diabetes gekoppel is aan immuunstelselverwante stres, het die navorsers voorgestel dat dit moontlik is dat immunisering prediabetiese pasiënte kan beskerm teen die aanvang van die volle siekte.

Dit is moontlik dat immunisering prediabetiese pasiënte kan beskerm teen die aanvang van die volle siekte.

"Dit is ongelooflik om te sien dat mense wat insulienweerstandig is, verskillend was, selfs by hul gesonde basislyn met verskeie mikrobiese verskille," het Snyder gesê.

Daar is bewyse wat daarop dui dat prediabetiese pasiënte 'n veranderde mikrobioom het wat ook blyk te wees gekoppel aan 'n verswakte immuunstelsel. Prediabetiese pasiënte kan baat vind by immunisering om hul immuunstelsel 'n hupstoot te gee, wat hulle in werklikheid beskerm teen die ontwikkeling van T2D. Slegs groter studies sal hierdie hipotese kan bevestig.

Toekomstige insigte

Die iHMP het die grootste versameling biologiese inligting oor mikrobiese gemeenskapsamestelling en geenuitdrukking, proteïene, metaboliete en immuunstelsel-eienskappe van beide die menslike liggaam en sy mikrobioom geproduseer, gevolg met verloop van tyd deur drie mikrobioomverwante toestande.

Deur biologiese kenmerke binne die menslike liggaam en sy mikrobioom op te spoor, het die iHMP-projekte aan die lig gebring dat verlies of wins van sekere mikrobes en hul eienskappe nou verband hou met die toestand van premature geboorte, IBD en prediabetes by individue.

In sommige gevalle het hierdie faktore as vroeë aanwysers van die siektes gedien en bied dus belofte vir die toekomstige ontwikkeling van voorspellende biomerkers.

Die reeks data wat in hierdie drie modelmikrobioomtoestande ingesamel is, dien as 'n hulpbron vir die groter gemeenskap om te toets watter biologiese faktore die mees insiggewende in hul spesifieke navorsing sal wees. Data van hierdie studies is geargiveer en saamgestel deur die HMP Data Coordination Centre en is beskikbaar vir onbeperkte gebruik vir verdere navorsing deur die breër gemeenskap.


INLEIDING

Die menslike mikrobioom is saamgestel uit bakterieë, archaea, virusse en eukariotiese mikrobes wat in en op ons liggame woon. Hierdie mikrobes het 'n geweldige potensiaal om ons fisiologie te beïnvloed, beide in gesondheid en in siekte. Hulle dra metaboliese funksies by, beskerm teen patogene, voed die immuunstelsel op, en beïnvloed deur hierdie basiese funksies direk of indirek die meeste van ons fisiologiese funksies.

Die studie van die menslike mikrobioom is bevorder deur tegnologiese vooruitgang vir die uitvoer van kultuur-onafhanklike ontledings (1). In die meeste studies word die bakteriese bestanddele van 'n mikrobiese populasie geïdentifiseer deur volgordebepaling van die 16S rRNA-koderende geen (hierna 16S) gevolg deur vergelyking met bekende bakteriële volgorde databasisse. Metagenomiese analise deur opeenvolging van alle mikrobiese DNA in 'n komplekse gemeenskap het die bykomende voordeel om die genetiese potensiaal van die mikrobiese populasie te assesseer. Ander metodologieë om die mikrobiese transkriptoom, proteoom en metaboloom te ontleed verskaf bykomende inligting op opeenvolgende vlakke van mikrobiese fisiologie (2). Ons gaan nie in hierdie spasie verder op spesifieke tegniese oorwegings in nie, maar belangstellende lesers word verwys na onlangse oorsigartikels (3-5).

Groot vordering met die karakterisering van die struktuur van die mikrobioom het onlangs die weg gebaan vir voortgesette en toekomstige studies oor die funksionele interaksies tussen die mikrobiota en die gasheer. Studies oor die funksie van die mikrobiota sal van kritieke belang wees om die rol van die mikrobiota in menslike homeostase en siektepatogenese te verstaan. In hierdie oorsig sal ons onlangse vooruitgang bespreek in ons begrip van die struktuur en funksie van die mikrobioom wat verband hou met die gesonde toestand en met spesifieke siek toestande.

Ophoping van data oor die menslike mikrobioom

Die geweldige uitbreiding van inligting wat die afgelope paar jaar oor die menslike mikrobioom ingesamel is, word beklemtoon deur data wat gegenereer is deur verskeie grootskaalse pogings om die menslike mikrobioom te karakteriseer, naamlik die Europese Metagenomics of the Human Intestinal Tract (MetaHIT) en die NIH-befondsde Human Microbiome Project (HMP) (6, 7). In 2010 het die aanvanklike MetaHIT-konsortiumstudie gerapporteer dat 3,3 miljoen nie-oortollige fekale mikrobiese gene opeenvolging gemaak is, wat byna 200 keer die hoeveelheid mikrobiese DNA-volgorde verteenwoordig wat in alle vorige studies aangemeld is (7). In Julie 2014 is 'n gekombineerde stel metagonomiese volgordebepalingdata van 1267 derm-metagenome van 1070 individue, insluitend 760 Europese monsters van MetaHIT, 139 Amerikaanse monsters van HMP en 368 Chinese monsters van 'n groot diabetesstudie, gepubliseer met 'n nie-oortollige geenkatalogus van 9,8 miljoen mikrobiese gene (*8). Elke monster het ongeveer 750 000 gene of ongeveer 30 keer die aantal gene in die menslike genoom bevat, en minder as 300 000 gene is deur meer as 50% van individue gedeel. Die meerderheid van die nuwe gene wat in hierdie jongste studie geïdentifiseer is, was relatief skaars, gevind in minder as 1% van individue. Daar word vermoed dat hierdie versameling byna 'n volledige stel gene bevat vir die meeste menslike dermbakterieë en illustreer die hoeveelheid en veranderlikheid van die menslike mikrobioom.

Struktuur en dinamika van die gesonde volwasse mikrobiota

Karakterisering van die mikrobioom in gesonde individue is 'n belangrike eerste stap in die begrip van die rol van die mikrobioom om by te dra tot gesondheid en siekte. Gesonde volwasse mense huisves gewoonlik meer as 1000 spesies bakterieë wat aan 'n relatief min bekende bakteriese filums behoort, met Bacteroidetes en Firmicutes as die dominante filums (9). Die mikrobiota van die derm is redelik uiteenlopend (Tabel 1) in vergelyking met ander liggaamsplekke, en daar is aansienlike variasie in die bestanddele van die dermmikrobiota onder oënskynlik gesonde individue (10). As 'n manier om die mikrobiese variasie onder gesonde individue te verantwoord, het navorsers probeer om sekere stabiele patrone van mikrobiese populasies in die menslike bevolking te identifiseer (11). Data van die HMP is gebruik om gemeenskapstipes by verskillende liggaamsplekke te identifiseer gebaseer op statistiese ontleding van die konfigurasie van veelvuldige bakteriese taksa (*12). Vier afsonderlike gemeenskappe is in die stoelgang gevind, en metadatafaktore wat met gemeenskapstipes geassosieer word, het borsvoeding, geslag en opvoeding ingesluit. Interessant genoeg was gemeenskapstipes in die mondholte voorspellende van dié in die stoelgang alhoewel die spesifieke bestanddele anders was. In 'n onlangse studie van 37 gesonde Amerikaanse volwassenes wat nie antibiotika neem nie, was meer as 70% van fekale bakteriese spesies binne 'n individu stabiel oor 1 jaar, en min bykomende veranderinge is tot 5 jaar gemeet (*13). Berekeninge het getoon dat spesies waarskynlik stabiel was oor dekades as nie vir 'n individu se hele leeftyd nie, soos blyk uit spesies wat met volwasse familielede gedeel word, maar nie met onverwante individue nie. Terwyl ons 'n diep begrip van die struktuur en dinamika van die mikrobioom in gesonde mense gekry het, word hierdie poging bemoeilik deur beduidende variasie in die populasie, beskeie variasie oor tyd binne 'n individu, en onsekerheid oor die mees betekenisvolle maniere om die mikrobiota te karakteriseer.

Tabel 1

TermynDefinisie
Rykdomdie aantal afsonderlike lede ("spesies") in die gemeenskap
Diversiteit'n maatstaf van die rykdom en gelykheid eienskappe van 'n gemeenskap, dikwels
bereken as 'n spesifieke "diversiteitsindeks"
Dysbiose'n term wat gebruik word om te verwys na 'n mikrobiota-gemeenskap wat met 'n siek geassosieer word
staat wat onderskei kan word van die mikrobiota gemeenskap wat geassosieer word
met 'n gesonde beheertoestand

Metaboliese funksies van die mikrobiota

Nadat mikrobiese gemeenskapslidmaatskap en dinamika gekarakteriseer is, is dit van kritieke belang om die funksionele aktiwiteite te verstaan ​​wat uiteindelik gasheerfisiologie beïnvloed. Ingewande mikrobiota is 'n integrale deel van gasheervertering en voeding, en hulle kan voedingstowwe genereer uit substrate wat andersins onverteerbaar is deur die gasheer. Xiloglukane word byvoorbeeld algemeen in dieetgroente soos blaarslaai en uie aangetref, en die kapasiteit vir mikrobiese vertering van xiloglukane is onlangs gekarteer na 'n enkele lokus in 'n sekere spesie van Bakteroides (*14). Daar is getoon dat die vermoë om xyloglukane te verteer 'n relatief seldsame eienskap in lede van die filum Bacteroidetes is, en die belangrikheid van hierdie vermoë vir die menslike gasheer is gedemonstreer deur ontleding van 'n publieke metagenoom databasis wat toon dat 92% van individue ten minste een van hierdie skaars Bakteroides spesies wat in staat is om xyloglukane te verteer. Hierdie bevindings illustreer hoe mense wedersyds voordelige verhoudings met dermmikrobiota gekweek het met implikasies vir dieet en voeding.

Mikrobes bevry kortkettingvetsure (SCFA) van onverteerbare dieetvesels, en SCFA is 'n belangrike energiebron vir dermslymvlies en krities vir die modulering van immuunresponse en tumorgenese in die derm. Die rol van butyraat, 'n oorvloedige bioaktiewe SCFA in die ingewande, speel 'n komplekse rol in kolonkanker wat blykbaar konsentrasie- en konteksafhanklik is, soos geïllustreer deur twee onlangse prekliniese studies. Daar is gerapporteer dat butiraat tumorgenese bevorder in transgeniese muise met gekombineerde tumoronderdrukker geen (APC) mutasie en wanpassing herstel geen (MSH2) tekort, omdat tumorvorming verminder is deur antibiotika behandeling of lae koolhidraat dieet, wat albei butiraatvlakke verlaag, en verhoog is met voeding van butyraat aan muise wat met antibiotika behandel is (*15). Omgekeerd, is gerapporteer dat butyraat tumorgenese inhibeer, omdat muise met 'n tekort aan Grp109a, 'n reseptor vir butiraat, verhoogde tumorgenese bevorder het deur inflammatoriese stimuli of APC-mutasie en sein deur Grp109a het tumorgenese geïnhibeer deur hierdie stimuli (*16). Verdere ondersoeke na die rol van butyraat wat deur mikrobiota in kolitis en kolorektale kanker geproduseer word, word gewag. Die studies wat in hierdie afdeling bespreek word, demonstreer die behoefte om die funksie van die mikrobiota te assesseer om die rol daarvan in gesondheid en siekte beter te verstaan.

Gasheer-mikrobe interaksies op die immuunstelsel

Interaksies tussen die mikrobiota en die gasheer-immuunstelsel is talryk, kompleks en tweerigting. Die immuunstelsel moet leer om die kommensale mikrobiota te verdra en gepas op patogene te reageer, en op sy beurt is die mikrobiota 'n integrale deel van die opvoeding van die immuunstelsel om behoorlik te funksioneer. Hier beklemtoon ons studies wat beskryf hoe lede van die mikrobiese gemeenskap die differensiasie van anti-inflammatoriese regulatoriese T-selle (Treg) bevorder om te illustreer hoe die mikrobiota immuunhomeostase kan beïnvloed. 'n Reeks eksperimente het getoon dat versamelings van nie-patogeniese spesies van Clostridia uit trosse IV, XIVa en XVIII, geïsoleer na toepassing van 'n reeks nie-spesifieke seleksiestappe, in staat was om kolon-Treg te induseer, en een meganisme kan die produksie van butyraat behels wat beïnvloed epigenetiese beheer van die Foxp3-promotor wat Treg-ontwikkeling beheer (17, **18, 19-22). In kiemvrye muise wat nie endogene mikrobiota bevat nie, het 'n ander groep ook 'n nuwe metode uitgedink om menslike fekale monsters te sif vir bakteriese stamme wat Treg-ontwikkeling kan bevorder, en hulle het hierdie funksionele kapasiteit in meer stamme opgemerk as wat verwag is (*23). Alhoewel dit nie hier bespreek word nie, is daar bewyse wat gasheer-mikrobe-interaksies uiteensit wat immuunfunksies op alle vlakke beïnvloed vanaf die aanvanklike aangebore verdediging tot die komplekse verworwe response wat in hierdie afdeling bespreek word (24). Daar is groot belangstelling om toe te lig hoe die mikrobiota immuunhomeostase binne en buite die ingewande kan beïnvloed, aangesien hierdie proses belangrike implikasies het vir die patogenese en behandeling van inflammatoriese versteurings en 'n groeiende lys van siektes wat met inflammasie verband hou.

Die rol van die mikrobiota in spesifieke siektes en toestande

Die bogenoemde afdelings het sommige van die vele maniere beskryf waarop die mikrobiota menslike fisiologie kan beïnvloed, en dit is geen verrassing dat daar groot belangstelling in die bestudering van mikrobiota veranderinge wat verband hou met siek toestande, dikwels na verwys as dysbiose (Tabel 1). Die verband tussen disbiose en siektepatogenese is egter onseker in die meeste voorbeelde op hierdie tydstip. Dit is dikwels nie duidelik watter mikrobiotaveranderinge wat met siekte geassosieer word, betekenisvol is nie en om tussen oorsaak en gevolg te onderskei is inherent uitdagend. Alhoewel dit intrigerend is om te spekuleer dat disbiose siekte kan veroorsaak, aangesien ons meer leer oor hoe die mikrobiota die gasheer kan beïnvloed, word daar ook opgemerk dat die siek toestand kan lei tot veranderinge aan die mikrobiota deur verskeie meganismes, insluitend veranderinge in eetgewoontes en ingewande funksioneer sowel as deur die byvoeging van medikasie soos antibiotika. In hierdie afdeling lig ons 'n paar van die onlangse bevindings oor die rol van die mikrobiota in spesifieke siektes of toestande uit, maar ons kan nie al die ontluikende bevindings in 'n menigte ander siektes binne en buite die ingewande aanraak nie, insluitend maar nie beperk tot rumatoïede artritis (25), kolorektale kanker (26), vetsug (27) en diabetes (28).

Kardiovaskulêre siekte

Daar is groeiende belangstelling in 'n verband tussen mikrobiota en kardiovaskulêre siektes gebaseer op data wat mikrobiese metabolisme van dieetfosfatidielcholien in die proaterosklerotiese metaboliet trimetielamien toon.N-oksied (TMAO) (29). 'n Onlangse studie van gesonde pasiënte wat met dieetfosfatidielcholien uitgedaag is, het verhoogde plasmavlakke van TMAO getoon wat deur voorafgaande behandeling met antibiotika onderdruk is. Hulle het ook bevind dat plasma TMAO-vlakke geassosieer word met verhoogde risiko vir kardiovaskulêre gebeure by pasiënte met kardiovaskulêre siekte risikofaktore (*30). In 'n ander studie het dieselfde groep getoon dat gesonde menslike vrywilligers wat 'n veganiese dieet handhaaf, in teenstelling met dié op omnivore dieet, nie verhoogde plasma TMAO-vlakke getoon het na dieet-fosfatidielcholien-uitdaging nie, en hierdie eienskap was geassosieer met spesifieke fekale mikrobiota samestelling toestande ( *31). Daar is dus baie belangstelling in hierdie mikrobiota-afhanklike pad wat diagnostiese en terapeutiese potensiaal vir kardiovaskulêre siekte kan bied.

Prikkelbare dermsiekte en die mikrobiota-derm-brein-as

'n Rol vir die mikrobiota in prikkelbare dermsindroom (IBS) word vermoed, alhoewel onbewese, en terapieë wat die mikrobiota verander, insluitend dieetveranderinge, probiotika en antibiotika, het bemoedigende, hoewel inkonsekwente, resultate getoon (32). In twee verslae wat die resultate van dieetintervensie met 'n lae FODMAP (f ermenteerbare o ligosakkariede, d isakkariede, m onosakkariede en poliole) beskryf wat bestaan ​​uit beperkte inname van sekere fermenteerbare substrate in vergelyking met 'n tipiese Australiese dieet in 'n klein aantal Australiese pasiënte met IBS, die lae FODMAP-dieet het simptome verbeter en gelei tot veranderinge in die dermmikrobiota, insluitend vermindering in vermoedelik gesonde bakterieë, soos dié in butyraatproduserende Clostridium cluster XIVa (33, *34). Een voorgestelde pad wat by IBS betrokke is, is deur 'n mikrobiota-derm-brein-as, wat veranderinge in die derm verbind met simptoompersepsie in die sentrale senuweestelsel. 'n Interessante onlangse verslag het getoon dat die inname van 'n probiotikaryke gefermenteerde melkproduk veranderinge in breinaktiwiteit tot gevolg gehad het in reaksie op visuele emosionele stimuli soos gemeet deur funksionele magnetiese resonansiebeelding in vergelyking met die inname van 'n kontroleproduk (35). Die studie van IBS is uitdagend as gevolg van die gebrek aan spesifieke diagnostiese toetse en die moontlikheid van heterogene etiologieë. Daar kan 'n subset van pasiënte wees waar mikrobiota veranderinge veral belangrik is en vir wie terapieë om mikrobiota samestelling en funksie te beïnvloed voordelig kan wees.

Clostridium difficile infeksie

Clostridium difficile infeksie (CDI) is die vernaamste voorbeeld van 'n menslike siekte wat ontwikkel as gevolg van kritieke veranderinge aan die dermmikrobiota en effektief behandel word deur mikrobiota-gebaseerde terapie (36). 'n Meta-analise om die gebruik van fekale mikrobiota-oorplanting (FMT) vir die voorkoming van herhalende CDI te hersien, het 11 studies met 273 pasiënte geïdentifiseer deur 2012, die algehele gevolglike doeltreffendheid was ongeveer 90% en geen aansienlike FMT-verwante nadelige gebeurtenisse is aangemeld nie (37). In 'n voornemende kliniese proef is pasiënte met herhalende CDI ewekansig aan een van drie behandelingsgroepe toegewys, standaard vankomisienterapie, vankomisienterapie gevolg deur dermspoeling, en vankomisienterapie gevolg deur dermspoeling en daaropvolgende infusie van skenkerstoelgang in die duodenum (** 38). Die studie is vroeg na tussentydse analise gestaak as gevolg van die meerderwaardigheid van FMT. Ontleding van die fekale mikrobiota van pasiënte wat met FMT vir herhalende CDI behandel is, het getoon dat die na-oorplanting mikrobiota van die ontvangers meer soortgelyk word aan dié van die skenker. After FMT the recipient microbiota was characterized by increased diversity, increased abundance of various Firmicutes and Bacteroidetes, and decreased abundance of Proteobacteria (*39). In a proof-of-principle study, two patients with CDI refractory to antibiotics were successfully treated with a stool substitute consisting of 33 strains of bacteria isolated and cultured from a healthy donor (*40). In this study, the stool substitute was delivered with colonoscopy, but it does provide promise for using a selected population of bacteria that could be prepared in a laboratory. Collectively, these studies strongly support the treatment of recurrent CDI with microbiota-based therapies.

While susceptibility to CDI after antibiotic use is associated with decreased microbiota diversity, little is known about the functional difference in the microenvironment that permits CDI. In preclinical studies, the microbiota changes that occurred after antibiotic treatment in mice susceptible to C. moeilikheid were accompanied by changes in the metabolome that supported C. moeilikheid germination and growth (*41). In the antibiotic-treated mice, primary bile acids that support C. moeilikheid germination and certain carbohydrates that support C. moeilikheid growth were present at significantly increased levels compared to control C. moeilikheid-resistant mice. This study, and others, are helping to unravel the mechanism by which antibiotic-induced changes to the microbiota contribute to CDI, potentially leading to novel therapies for this burdensome disease.

Inflammatoriese dermsiekte

Inflammatory bowel diseases (IBD) are characterized by inappropriate inflammation in the gut resulting from a combination of environmental and genetic risk factors. Targets of the inflammatory response include the commensal microbiota, and IBD are associated with alterations in the gut microbiota, though it is not clear if microbial changes contribute to disease pathogenesis or develop as a result of local inflammation (42). Here, we highlight two recent publications describing the microbiome and host response measured in treatment naïve pediatric patients with newly diagnosed IBD that provide early findings not confounded by anti-inflammatory therapies.

In the first report, 447 treatment naïve pediatric Crohn’s disease (CD) patients and 221 controls were included in a study where the microbiome from multiple sites was characterized by 16S sequence analysis (**43). Multivariate analysis identified microbial taxa significantly associated with disease phenotype in ileal and rectal samples but not from stool samples. The microbiome of CD patients had a lower diversity, increased abundances of Enterobacteriaceae, Pasteurellaceae, Fusobacteriaceae, Neisseriaceae, Veillonellaceae, and Gemellaceae, and decreased abundances of Bifidobacteriaceae, Erysipelotrichaceae, Clostridiales, and Bacteroidales. Using these microbiome-disease associations, they formulated a microbial dysbiosis index that showed a strong positive correlation with clinical disease activity (PDCAI) and a negative correlation with species richness ( Table 1 ). In addition, microbiome comparison between CD patients with and without antibiotic exposure revealed that antibiotic use amplifies the microbial dysbiosis associated with CD. Of note, the authors demonstrate that many of their observations were only seen when analyzing hundreds of samples, emphasizing the importance of large-scale studies.

In the next report, host gene expression and the microbiome were characterized from the ileum of treatment naïve pediatric patients with ileal CD (iCD), colonic CD (cCD), and ulcerative colitis (UC) as well as controls (**44). A core iCD gene expression signature of 1281 genes was identified by comparing iCD and control groups. Upregulated genes included those induced by bacterial products and proinflammatory signals, and downregulated genes included nuclear receptors involved in metabolic pathways and anti-inflammatory signaling. Interestingly, the cCD group, including those without any microscopic inflammation, had a similar expression pattern in the ileum to the iCD group, and this pattern was different from control and UC groups, indicating a core CD gene expression profile in the ileum independent of inflammation. Similarly, iCD and cCD groups had similar profiles of dysbiosis that was different from control and UC groups. Of note, an increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. Finally, multivariate analysis showed correlations between bacterial taxa, gene expression and clinical disease activity scores in CD patients irrespective of the presence of ileal inflammation, and a prediction model based on gene expression, microbe abundance and clinical factors outperformed clinical disease activity scores alone in predicting response to therapy.

These studies provide additional information towards understanding a potential role of the microbiota in the pathogenesis of IBD that has not been established to date. This stands in contrast to CDI where microbiota alterations clearly increase the risk for disease and restoration of a diverse microbiota with FMT clearly prevents disease recurrence in most patients. Early efforts to utilize FMT for the treatment of IBD have been rather disappointing (45, 46). It seems quite likely that the role of microbiota in IBD, and other multigenic traits, will prove to be more complex and depend on specific genetic susceptibilities and certain environmental factors. Therefore, it will be important to further characterize the microbiota population and its functions at various time points in IBD development in conjunction with assessments of host susceptibility, host response and environmental exposures.


You may be damaging your body's ecosystem and not know it

One of the hottest topics in medicine concerns the relationship between the body's bacteria and a range of serious diseases -- from cancer to obesity. Georgetown University Hospital gastroenterologist Dr. Robynne Chutkan said our squeaky-clean lifestyle is wreaking havoc on those vital bacteria and damaging our health.

"We are super sanitizing ourselves into illness and thinking that we are being clean and preventing disease we're actually causing disease by disrupting the microbiome," Chutkan said Wednesday on "CBS This Morning."

Her new book, "The Microbiome Solution: A Radical New Way to Heal your Body from the Inside Out," explores the microbiome, a term that refers to the over 100 trillion microbes -- bacteria, viruses and fungi -- that live in and on the human body.

"The vast majority of the microbes that live in our bodies are a vital part of our ecosystem and they're essential to our health. They're not disease-causing germs as we've been taught," she said.

In fact, imbalance to the microbiome, or dysbiosis, has been linked to a range of health problems including certain types of cancer autoimmune diseases like thyroid disorders, multiple sclerosis and type 1 diabetes as well as gastrointestinal disorders like Crohn's disease and irritable bowel syndrome.

Chutkan said studies have also revealed an altered microbiome in some children with autism.

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Dysbiosis affects up to 30 million Americans, according to Chutkan. She said symptoms of microbiome imbalance include bloating, food intolerance, skin rashes, brain fog and weight-loss resistance.

In addition to hyper-sanitizing our environment with antibacterial cleaning products, a number of drugs contribute to dysbiosis.

Antibiotics are the primary cause for concern, according to Chutkan.

"Five days of a typical, broad-spectrum antibiotic can remove up to one-third of your gut bacteria and there's no guarantee that these species come back," Chutkan said.

Many doctors recommend probiotics to combat those effects, but Chutkan said taking a probiotic does not fix the damage done by an antibiotic.

"Taking a probiotic after that is like draining out the entire bath of water and then putting in a cup of water and thinking 'OK, I'm fixed,'" she said. Furthermore, not all probiotics are the same and it's important to pick the right strain.

Other drugs like steroids, hormones, acid-blockers and NSAID pain relievers -- ibuprofen, for example -- can damage the microbiome, which may lead to damage of the intestinal lining and other organ systems, she said.

What can we do to keep our microbiome happy?

"We need to eat food that feeds our gut bacteria, what we called prebiotic foods," Chutkan said.

Foods like garlic, asparagus, leeks, onion, oats, lentils and artichokes, as well as fermented foods like sauerkraut, kimchi and pickles all act as prebiotics.

Her book also includes information on fecal microbiome transplant, a therapy that has shown increasing success in treating certain intestinal infections. Chutkan said there's also evidence that it could be used to treat certain autoimmune disorders.


The role of the microbiome in human health and disease: an introduction for clinicians

Research into the microbiome—the indigenous microbial communities (microbiota) and the host environment that they inhabit—has changed clinicians’ ideas about microbes in human health and disease. Perhaps the most radical change is the realization that most of the microbes that inhabit our body supply crucial ecosystem services that benefit the entire host-microbe system. These services include the production of important resources, bioconversion of nutrients, and protection against pathogenic microbes. Thus disease can result from a loss of beneficial functions or the introduction of maladaptive functions by invading microbes. This review will show how an understanding of the dynamics and function of the indigenous microbiota has altered our view of microbes in maintaining homeostasis and causing disease. It will discuss how disruption of the beneficial functions of the microbiota can lead to disease. Methods for studying the microbiota will be introduced as part of a conceptual framework for using these methods to delineate novel roles for microbes in health. Key associations between specific changes in the microbiome and disease will be discussed. This will lead to an explanation of how the intentional manipulation of the microbiota, either by restoring missing functions or eliminating harmful functions, may lead to novel methods to prevent or treat a variety of diseases. With the explosion of studies relating the microbiome to health and disease, this review aims to provide a foundation for clinicians to follow this developing area of biomedical research.


Human microbiome could shed light on higher morbidity rate in minoritized populations

Credit: Pixabay/CC0 Public Domain

The human gut is more than a source of instinct.

A new Northwestern University study is the first to explicitly address the gut microbiome as a pathway to understanding how environmental inequities could lead to health disparities.

Biological anthropologist Katherine Amato, assistant professor of anthropology at the Weinberg College of Arts and Sciences at Northwestern, is the study's lead author.

Amato says, despite a rich body of literature documenting environmental impacts on the microbiome, and the microbiome's impact on human health, the links between structural discrimination, altered environments, microbiome structure and health disparities have not been comprehensively outlined.

The new study calls for a better understanding of how structural discrimination that exposes minoritized populations to 'unhealthy' environments—from altered diets, pollution, sanitation and lack of access to green space—impacts the human gut microbiome, which in turn affects almost every aspect of human biology and health.

"Research has implicated the microbiome in most chronic diseases, and we know that there are disparities in most chronic diseases in which higher morbidity is observed in minoritized populations," Amato said.

Prior studies have demonstrated the impact of environmental inequality on health. For example, a 2020 study showed that children who are exposed to plants and dirt daily at school have higher microbial diversity and improved immune markers, likely because the exposure to microbes in these materials are transmitted to children's bodies. The pattern suggests that minoritized populations living in neighborhoods with little access to outdoor green space are more likely to have lower microbial diversity and associated health risks.

Among its many roles, the gut microbiome contributes to protection from pathogens, nutrition and metabolism, immune function, brain development and behavior. An altered gut microbiome can also have an impact on the gestational environment and the resulting health of the next generation.

Amato's study builds on prior research that shows the environment's role may be stronger than genetics in shaping the human microbiome, and that changes to the composition and function of the microbiome are most flexible in early life.

According to Amato, more empirical and interdisciplinary research is needed to facilitate epidemiological approaches that can tease apart multiple interacting determinants of health and help isolate the factors leading to chronic disease.

An ultimate goal of the research is to be able to deliver interventions that address environmental issues and individualized therapies to restore and improve microbiome health.

"Demonstrating the potential importance of these therapies in combatting health inequities could lead to transformative policy interventions that strive for universal access to emerging health technologies, and to healthcare more generally," Amato said.

"The human gut microbiome and health inequities" will publish June 14 in the journal Verrigtinge van die National Academy of Sciences (PNAS).


The role of the microbiome in human health and disease: an introduction for clinicians

Research into the microbiome—the indigenous microbial communities (microbiota) and the host environment that they inhabit—has changed clinicians’ ideas about microbes in human health and disease. Perhaps the most radical change is the realization that most of the microbes that inhabit our body supply crucial ecosystem services that benefit the entire host-microbe system. These services include the production of important resources, bioconversion of nutrients, and protection against pathogenic microbes. Thus disease can result from a loss of beneficial functions or the introduction of maladaptive functions by invading microbes. This review will show how an understanding of the dynamics and function of the indigenous microbiota has altered our view of microbes in maintaining homeostasis and causing disease. It will discuss how disruption of the beneficial functions of the microbiota can lead to disease. Methods for studying the microbiota will be introduced as part of a conceptual framework for using these methods to delineate novel roles for microbes in health. Key associations between specific changes in the microbiome and disease will be discussed. This will lead to an explanation of how the intentional manipulation of the microbiota, either by restoring missing functions or eliminating harmful functions, may lead to novel methods to prevent or treat a variety of diseases. With the explosion of studies relating the microbiome to health and disease, this review aims to provide a foundation for clinicians to follow this developing area of biomedical research.


Gut Microbiota and COVID-19 Disease Severity

Although COVID-19 primarily compromises the lungs, it also affects other parts of the body, including the gut . Gastroenterologist Ajiz Ahmed and colleagues at Stanford University showed that patients with GI symptoms were five times more likely to be admitted to the hospital — a connection that begins to make sense when we understand what the gut and lungs have in common.

As different as the roles of the gut and lungs are, they share some of the same basic structural features because they develop from the same embryonic tissues. For example, they are both lined with mucous membranes — a thin layer of specialized cells that lubricate and protect against pathogens — and they are both part of the same mucosal immune system , an integrated immune network that protects the body from infection.

COVID-19 enters cells by binding to angiotensin-converting enzyme 2 ( ACE2 ) receptors on the surface of cells throughout the body. ACE2 is a protein involved in normal biological processes, including blood pressure regulation, wound healing, and inflammation. COVID-19 uses ACE2 receptors as a doorway to enter cells and start replicating. In the process, the normal functions of ACE2 receptors are blocked. Cells that line the gut and lungs are particularly vulnerable to COVID-19 infection because they have many ACE2 receptors. People who have pre-existing deficits in their microbiota tend to have more ACE2 receptors. This may increase their susceptibility to inflammation and to COVID-19 infection, especially more severe cases.

Microbiologist and immunologist Gregor Reid of Western University in Canada says that “inflammation in the gut and lungs [can] provide the virus access to distant sites and potentially [contribute to] poorer patient outcomes.” For example, inflammation damages the cellular structure of the gut’s lining, undermining its ability to act as a protective barrier. In this way, pathogens may exit the gut, enter the bloodstream, access other organs expressing ACE2, and trigger inflammation in distant parts of the body. Other scientists are hypothesizing that disruption of the gut’s mucosal barrier may lead to severe COVID-19 for this very reason.

Reid cautions that the severity of COVID-19 symptoms likely depends on many variables and interactions that are still not entirely clear. For example, certain individuals may be more susceptible to severe COVID-19 based on the pre-existing status of their gut microbiota and their susceptibility to inflammation, Reid says. Even medications that a patient takes could alter their gut microbiota and influence COVID-19 infection and severity.

Gastroenterologist Siew Chien Ng and researchers at the Chinese University of Hong Kong found that certain bacteria known to reduce inflammation were depleted in COVID-19 patients who had elevated inflammatory markers in their blood, regardless of whether they received medications.


Parkinson's Disease Linked to Microbiome

Caltech scientists have discovered for the first time a functional link between bacteria in the intestines and Parkinson's disease (PD). The researchers show that changes in the composition of gut bacterial populations&mdashor possibly gut bacteria themselves&mdashare actively contributing to and may even cause the deterioration of motor skills that is the hallmark of this disease.

The work&mdashwhich has profound implications for the treatment of PD&mdashwas performed in the laboratory of Sarkis Mazmanian, the Luis B. and Nelly Soux Professor of Microbiology and Heritage Medical Research Institute Investigator, and appears in the December 1 issue of Sel.

PD affects 1 million people in the US and up to 10 million worldwide, making it the second most common neurodegenerative disease. Characteristic features of PD include symptoms such as tremors and difficulty walking, aggregation of a protein called alpha-synuclein (αSyn) within cells in the brain and gut, and the presence of inflammatory molecules called cytokines within the brain. In addition, 75 percent of people with PD have gastrointestinal (GI) abnormalities, primarily constipation.

"The gut is a permanent home to a diverse community of beneficial and sometimes harmful bacteria, known as the microbiome, that is important for the development and function of the immune and nervous systems," Mazmanian says. "Remarkably, 70 percent of all neurons in the peripheral nervous system&mdashthat is, not the brain or spinal cord&mdashare in the intestines, and the gut's nervous system is directly connected to the central nervous system through the vagus nerve. Because GI problems often precede the motor symptoms by many years, and because most PD cases are caused by environmental factors, we hypothesized that bacteria in the gut may contribute to PD."

To test this, the researchers utilized mice that overproduce αSyn and display symptoms of Parkinson's. One group of mice had a complex consortium of gut bacteria the others, called germ-free mice, were bred in a completely sterile environment at Caltech and thus lacked gut bacteria. The researchers had both groups of mice perform several tasks to measure their motor skills, such as running on treadmills, crossing a beam, and descending from a pole. The germ-free mice performed significantly better than the mice with a complete microbiome.

"This was the 'eureka' moment," says Timothy Sampson, a postdoctoral scholar in biology and biological engineering and first author on the paper. "The mice were genetically identical both groups were making too much αSyn. The only difference was the presence or absence of gut microbiota. Once you remove the microbiome, the mice have normal motor skills even with the overproduction of αSyn."

"All three of the hallmark traits of Parkinson's were gone in the germ-free models," Sampson says. "Now we were quite confident that gut bacteria regulate, and are even required for, the symptoms of PD. So, we wanted to know how this happens."

When gut bacteria break down dietary fiber, they produce molecules called short-chain fatty acids (SCFAs), such as acetate and butyrate. Previous research has shown that these molecules also can activate immune responses in the brain. Thus, Mazmanian's group hypothesized that an imbalance in the levels of SCFAs regulates brain inflammation and other symptoms of PD. Indeed, when germ-free mice were fed SCFAs, cells called microglia&mdashwhich are immune cells residing in the brain&mdashbecame activated. Such inflammatory processes can cause neurons to malfunction or even die. In fact, germ-free mice fed SCFAs now showed motor disabilities and αSyn aggregation in regions of the brain linked to PD.

In a final set of experiments, Mazmanian and his group collaborated with Ali Keshavarzian, a gastroenterologist at Rush University in Chicago, to obtain fecal samples from patients with PD and from healthy controls. The human microbiome samples were transplanted into germ-free mice, which then remarkably began to exhibit symptoms of PD. These mice also showed higher levels of SCFAs in their feces. Transplanted fecal samples from healthy individuals, in contrast, did not trigger PD symptoms, unlike mice harboring gut bacteria from PD patients.

"This really closed the loop for us," Mazmanian says. "The data suggest that changes to the gut microbiome are likely more than just a consequence of PD. It's a provocative finding that needs to be further studied, but the fact that you can transplant the microbiome from humans to mice and transfer symptoms suggests that bacteria are a major contributor to disease."

The findings have important implications for the treatment of Parkinson's, the researchers say.

"For many neurological conditions, the conventional treatment approach is to get a drug into the brain. However, if PD is indeed not solely caused by changes in the brain but instead by changes in the microbiome, then you may just have to get drugs into the gut to help patients, which is much easier to do," Mazmanian says. Such drugs could be designed to modulate SCFA levels, deliver beneficial probiotics, or remove harmful organisms. "This new concept may lead to safer therapies with fewer side effects compared to current treatments."

The paper is titled "Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease." Other Caltech coauthors include Taren Thron, Gnotobiotic Facility manager and research technician for the Mazmanian laboratory undergraduate Gauri G. Shastri postdoctoral scholar Collin Challis graduate student Catherine E. Schretter and Viviana Gradinaru, assistant professor of biology and biological engineering and Heritage Medical Research Institute Investigator. The work was funded by the Larry L. Hillblom Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council, Mr. and Mrs. Larry Field, the Heritage Medical Research Institute, and the National Institutes of Health.


Transkripsie

Bakterieë. Virusse. Swamme. We normally think of these organisms as our enemies.

But they aren’t all bad. Our bodies are full of them and it turns out we can’t live without them. But what exactly are they and what do they do for us?

From the moment we’re born, we acquire, and nurture an internal ecosystem of symbiotic bacteria and other microbes, trillions of them in all. In fact there are roughly as many microbial cells in our bodies as human cells. This thriving microbial world is called our microbiome.

While some microbes can make us ill, we need our microbiome to survive. Combined, they are every bit as essential as our heart, our lungs or our brain.

We have microbes living all over our skin and in every orifice of our bodies. But most of the microbiome is found in our gut. Our gut microbes are essential for digestion. They also help regulate hormones and they can boost our immune system.

Our microbiome contains a wide range of microbes, some of which have beneficial effects on our health and some of which are detrimental. A healthy collection of microbes seems to be vital for our wellbeing, protecting against some of the biggest health threats, like heart disease, obesity, diabetes, arthritis and even depression.

On the other hand, having an unhealthy microbiome may be a contributing factor for many common diseases.

Our modern lifestyles, western diets and overuse of antibiotics might all be having a harmful effect on our internal ecology.

So how do you cultivate a healthy microbiome? Well it seems that the more diverse your microbial population is, the better. And the best way to increase your diversity is to eat a wide range of plant-based foods.

Research shows that people who have at least 30 plant-based elements in their diet every week have a wider range of bacteria in their gut, and that’s linked to better weight management, better heart health and better mental health.

One easy way to boost your numbers is to add a teaspoon of mixed seeds to your breakfast – each type of seed counts as one of the elements. Whole grains, nuts and legumes are all good things to add to your diet as well.

For a few very unlucky people, your microbiome can go badly awry. For years, a man in the US experienced unexplained mental fogginess, dizziness and memory loss. He was repeatedly pulled over for drink driving, even when he said he hadn’t touched any alcohol.

Finally he was diagnosed with a very rare condition called auto-brewery syndrome, which happens someone’s gut gets colonised by Saccharomyces cerevisiae, also known as brewer’s yeast. These yeasts convert carbohydrates into alcohol, so this man was brewing beer inside his own stomach. That might sound fun, but this guy will tell you it really isn’t.

You can learn more about how your microbiome affects your health by subscribing to Nuwe wetenskaplike. We’ve even got a special discount for our wonderful YouTube viewers: click the link in the box below and enter the code SAM20 to get 20 per cent off.

The influence of your gut microbes goes a lot further than you might think. In the last 20 years, we’ve learned that they communicate constantly with the brain, perhaps even exerting control over your mood and emotions.

In fact, microbes can produce every neurotransmitter found in the human brain, including serotonin and dopamine. And there are cells in the gut lining that can detect neurotransmitters and send signals to the brain.

Studies have found that when human volunteers are given probiotic yoghurts containing four different types of bacteria, this affects the activity and connectivity in emotion centres in the brain, producing changes linked to healthier emotion processing.

Another study found that pregnant women who were given certain bacteria had lower scores on depression and anxiety tests compared with a control group. Research like this has led to the idea that mental illness could be treated using treatments that change our gut bacteria, which have been dubbed psychobiotics.

Your microbiome is a big part of who you are. So take care of it, and it will take care of you! If you enjoyed this video don’t forget to like and subscribe for more Science with Sam.


Kyk die video: Retke bolesti - Metabolički poremećaji (September 2022).