The fungus Candida albicans can live harmlessly in our guts, where it exists in a dynamic relationship with the huge numbers of other microorganisms that are also present in the gut (microbiota), and with our immune system. When this relationship gets disrupted e.g. when our immune systems are dampened, or long courses of broad-spectrum antibiotics deplete our microbiota, Candida albicans can cause serious infections. It can cause thrush in the vagina which effects 70% of women at least once during their lifetime and approximately 8% of these women suffer from recurring infections. Many HIV+ individuals experience thrush in the mouth at some point during their lifetime. These diseases reduce the quality of people’s lives, and in the case of systemic infection it can be life threatening. Systemic infection is caused by Candida entering the bloodstream and leads to more than 50,000 deaths per year worldwide and is a major burden on the healthcare system. The problem of Candida infections has the potential to become even worse in the future as these fungi are showing increasing resistance to antifungal drugs, so it is important to find other ways of preventing infection from Candida living in our gut.
Previous studies have provided the proof of concept that it is possible to cure infections by manipulating the bacterial community in the gut. For example, faecal microbiota transplants have been proven to cure antibiotic resistant Clostridioides difficile infections. However, very little has yet been done to develop a similar therapeutic approach towards fungal infections like Candida. Thus, this project, as part of the FunHoMic Innovative Training Network, looks at the microbiota as a therapeutic target for the prevention of C. albicans infections. It aims to investigate the molecular mechanisms utilised by specific gut bacteria to inhibit the growth of C. albicans. The ultimate aim is to identify prime candidates that might subsequently be developed as live biotherapeutic products (LBPs) These candidate LBPs will be assessed for their effectiveness in order to provide proof of principle that they may reduce the risk of systemic infection or vaginitis caused by C. albicans.
Is féidir leis an fungas Candida albicans maireachtáil go neamhdhíobhálach inár n-inní, áit a bhfuil sé i gcaidreamh dinimiciúil leis an líon mór miocrorgánach eile atá i láthair sa ghoile (microbiota), agus lenár gcóras imdhíonachta. Nuair a chuirtear isteach ar an gcaidreamh seo m.sh. nuair a dhéantar dampened ar ár gcórais imdhíonachta, nó nuair a ídíonn cúrsaí fada de antaibheathaigh speictrim leathan ár micribhiota, is féidir le C. albicans ionfhabhtuithe tromchúiseacha a chruthú. Féadann sé smólach a chur faoi deara sa vagina a mbíonn tionchar aige ar 70% de na mná uair amháin ar a laghad le linn a saoil agus bíonn ionfhabhtuithe athfhillteacha ag thart ar 8% de na mná seo. Bíonn an smólach i mbéal an-chuid daoine HIV+ ag am éigin le linn a saoil. Laghdaíonn na galair seo caighdeán saoil daoine, agus i gcás ionfhabhtaithe sistéamaí is féidir leis a bheith bagrach don bheatha. Is é Candida ag dul isteach i sruth na fola is cúis le hionfhabhtú córasach agus bíonn níos mó ná 50,000 bás ann in aghaidh na bliana ar fud an domhain agus is ualach mór é ar an gcóras cúraim sláinte. Tá an poitéinseal ag fadhb na n-ionfhabhtuithe Candida a bheith níos measa fós sa todhchaí toisc go bhfuil friotaíocht mhéadaitheach ag drugaí na bhfungas seo do dhrugaí antifungal, mar sin tá sé tábhachtach bealaí eile a aimsiú chun cosc a chur ar ionfhabhtú ó Candida a chónaíonn inár n-inní.
Chuir staidéir roimhe seo cruthúnas ar choincheap ar fáil gur féidir ionfhabhtuithe a leigheas trí an pobal baictéarach sa ghoile a ionramháil. Mar shampla, cruthaíodh go gcruthóidh trasphlandú microbiota faecach leigheasanna ionfhabhtaíocha Clostridioides difficile atá frithsheasmhach in aghaidh antaibheathach. Mar sin féin, is beag a rinneadh fós chun cur chuige teiripeacha den chineál céanna a fhorbairt i leith ionfhabhtuithe fungais cosúil le Candida. Dá bhrí sin, mar chuid den “FunHoMic Innovative Training Network”, féachann an tionscadal seo ar an microbiota mar sprioc theiripeach chun ionfhabhtuithe C. albicans a chosc. Is é an aidhm dheiridh príomh-iarrthóirí a aithint a d'fhéadfaí a fhorbairt ina dhiaidh sin mar "live biotherapeutic products” (LBPs). Déanfar measúnú ar a n-éifeachtúlacht maidir leis na LBPs is iarrthóirí chun cruthúnas prionsabal a sholáthar go bhféadfadh siad an baol ionfhabhtaithe sistéamaí nó vaginitis de bharr C. albicans a laghdú.