Abstract
The gastrointestinal (GI) tract is a highly complex organ composed of the intestinal epithelium layer, intestinal microbiota, and local immune system. Intestinal microbiota residing in the GI tract engages in a mutualistic relationship with the host. Different sections of the GI tract contain distinct proportions of the intestinal microbiota, resulting in the presence of unique bacterial products in each GI section. The intestinal microbiota converts ingested nutrients into metabolites that target either the intestinal microbiota population or host cells. Metabolites act as messengers of information between the intestinal microbiota and host cells. The intestinal microbiota composition and resulting metabolites thus impact host development, health, and pathogenesis. Many recent studies have focused on modulation of the gut microbiota and their metabolites to improve host health and prevent or treat diseases. In this review, we focus on the production of microbial metabolites, their biological impact on the intestinal microbiota composition and host cells, and the effect of microbial metabolites that contribute to improvements in inflammatory bowel diseases and metabolic diseases. Understanding the role of microbial metabolites in protection against disease might offer an intriguing approach to regulate disease.
Highlights
The gastrointestinal (GI) tract is a highly complex organ composed of the intestinal epithelium layer, microorganisms, and local immune system
The GI tract contains high levels of multiple microbial metabolites, which can interact with the host cells and, in particular, cells localized to the intestinal tract, including intestinal epithelial cells (IECs) and local immune cells [11,86,87]
They act as signaling molecules by activating the nuclear receptor farnesoid X receptor (FXR) or the plasma membrane receptor G-protein–coupled receptor 5 (TGR5), which are expressed on IECs in the small intestine and colon [44,126]; for example, microbial bile acid derivatives deoxycholic acid (DCA) and lithocholic acid (LCA) bind to FXR and regulate IEC integrity [127]
Summary
The gastrointestinal (GI) tract is a highly complex organ composed of the intestinal epithelium layer, microorganisms, and local immune system. The intestinal microbiota is a microbial organ within the host as it is composed of different bacterial populations with the specific ability to communicate with each other and with the host cells [6]. The intestinal microbiota has co-evolved with the host, providing specific genetic and metabolic attributes. The microbiota contains anaerobic bacteria that break down ingested polysaccharides, the most abundant biological polymer, supplying carbon and energy resources for its own growth and for the host [7]. Different sections of the GI tract contain distinct populations of the intestinal microbiota [8,9]. Variation in intestinal microbial communities might be associated with differences in ingested foods and the host GI environment. Km);e[t1a3b]omliteetsaboof lditieestasreycrceotmedpboynetnhteshthoastt caerlel tarnadnsmfoordmiefidedbybythteheinitnetsetsintianlaml micircorboiboitoata(e(.eg..g, .c,osmecpoonudnadry bKile);a[1c3id]sm);e[t1a4b]omliteetsasbeoclriteetsedthbayt tahree hsyonstthceelslizaendd bmyotdhiefieindtebsytitnhaelimntiecsrtoinbaioltma idceronboiovtoa((ee..gg..,, sshecoortn-dchaaryin fabtitlye acids)(;S[1C4F]Amse)t[a1b5o,1li6t]e.sMthoarteaorveesry, nmthicersoizbeiadlbmyetthaebionltiteesstianrael mnoitcroonbliyotlaocdaelinzoedvoin(et.hge., sGhIotrrta-cht,abinut aflsaottybraocaidsly(SpCeFnAetsr)at[e15h,1o6s]t.tMissoure,opvreirm, mariiclryotbhiarol umgehtatbhoelsitmesaallreinnteosttoinnely[1lo7]c.aTlizheedeiffnetcht eofGmI tertaacbt,obliutets oanlstohebrhooasdtlyceplle,nseutrcahteashothstetipsrsoume,optriiomnaoriflyintthersotiungahl tehpeitshmealilallinretegsetnineera[1ti7o].nTahnedefbfeacrtrioefrminetteagbroiltiyteosr thoen rtehgeuhloastitocnelol,fsumcuhcaosstahleimprmomunoetiohnomofeionstetasstiins,aldeeppiethnedlsiaol nretgheenetarargtieotncaenlldtybpareri[e1r8i,n19te]g. rTithyeorerftohree, thregcuolmatpioonsiotifomn uofcothsaeliinmtemstuinnael hmoimcreoobsitoatsaisi,mdpeapcetnsdhsosotndtehveeltoarpgmetencet,llhteyaplteh[,1a8n,1d9d].isTehaesree.fore, the comRpeocseitniotlny,omf thaneyinstetustdinieasl mhaicvreobfiooctuasiemdpaocntsthoestmdoedvueloaptimonenotf, hineateltshti,naanldmdisceroasbei.ota and their metabRoelictenstfloyr, hmeanltyh ismtupdrioevs ehmaevnet faoncdusdeidseoasne tphreevmenotdiounlaotirontreoaftminetnets.tiHnaelremini,crwoebiaoitma taondprothveidire amn oetvaebrovliietews ofofruhpe-atolt-hdaimtepsrtouvdeimesehnitgahnlidghdtiisnegasteheprpeovteennttiioanl iomrptrleamtmenetnat.ioHneorefimn,ewtaebaoilmitetsofoprrohveiadlteh aanndodviesrevaiseewimofpurpo-vteom-deantet.stFuudritehsehri,gwhleigfhoctiunsg othnetphoetpenrotidaluicmtipolnemofenmtaictrionbioafl mmeettaabbooliltietessfoarnhdetahltehir baionldogdiicsaelaisme pimacptroonvethmeeinntt.eFsutirntahlemr, iwcreobfoiocutas coonmtphoespitriodnuacntidonhoosft mceilclrso, baisawl melel taasbtohlietecsonantrdibtuhteioirn obf imoleotgaibcaoliitmesptaoctthoen othneseint toefstininflaalmmmicraotobrioytabocwomelpdoissietiaosnesan(IdBhDoss)t, nceolnls-,aalcsowheolllicasfathtteycloivnetridbuisteioanse (NofAmFLetDab),oolibtesitoy, tahnedomnseettaboof liincfdlaimsemasaetso.ry bowel diseases (IBDs), non-alcoholic fatty liver disease (NAFLD), obesity, and metabolic diseases
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