Khungu la microbiome la mitundu yonse ya EB (2023)

Chidziwitso chatsopano chomwe chavumbulutsidwa mu polojekitiyi chimafotokoza kuti ndi tizilombo ting'onoting'ono (mabakiteriya, bowa ndi ma virus) omwe amakhala pakhungu. Nambala ndi mtundu zimapanga 'microbiome' ya khungu. Kuyerekeza kusintha kwa ma microbiome a khungu lotupa komanso lopanda matuza la anthu omwe ali ndi mitundu yosiyanasiyana ya EB komanso opanda mitundu yosiyanasiyana ya EB adazindikira mawonekedwe omwe adasintha pakuchiritsa mabala.

Maselo a chitetezo cha mthupi (neutrophils) ochokera ku zitsanzo za magazi adapezeka kuti akugwira ntchito kwambiri, makamaka ku JEB, kotero kuti mankhwala omwe amachititsa kuti khalidwe la maselowa likhale lolimba likhoza kufufuzidwa ngati mankhwala ochiritsira.

Puloteni yeniyeni yomwe imapezeka m'madzi amadzimadzi kuchokera kwa anthu opanda EB omwe anali kusowa kwa anthu omwe ali ndi EB angakhalenso chandamale chatsopano chamankhwala.

Mu Disembala 2023, Prof Chapple adasindikiza zotsatira kuchokera ku ntchito zothandizidwa ndi DEBRA UK zotchedwa Kulumikizana kwa Genotype-phenotype mu Junctional Epidermolysis Bullosa: zikwangwani mpaka kuuma. Izi zidanenedwanso mu nkhani ya anthu onse.

"Kafukufuku wathu wapititsa patsogolo kumvetsetsa kwaposachedwa kwa magwiridwe antchito akhungu, mapuloteni a blister komanso machitidwe a neutrophil mu EB angachiritse. Izi zitha kupangitsa kuti pakhale mavalidwe atsopano komanso njira zochiritsira monga kupanga ma pre- ndi ma probiotics ”

Prof Iain Chapple

Zitsanzo 94 za swab zapakhungu zasonkhanitsidwa ndipo kusanthula kwa microbiome kwayamba. Zotsatira zoyambirira zimasonyeza kusiyana kwa mitundu ya mabakiteriya omwe amakhala m'madera osiyanasiyana a thupi komanso kusiyana pakati pa khungu la anthu omwe ali ndi DEB ndi JEB poyerekeza ndi anthu opanda EB.

Zitsanzo za 16 za EB blister fluid zasonkhanitsidwa ndikuphunziridwa kuti zitsimikizire kuti ndi mapuloteni ati a chitetezo cha mthupi (cytokines) omwe amachulukitsidwa kapena kuchepetsedwa. Izi zapereka umboni wina wosonyeza kuti chitetezo cha mthupi chikhoza kuwononga m'malo mochiritsa mitundu ina ya EB.

A chojambula Kufotokozera mwachidule zomwe zikuchitika mpaka pano zidaperekedwa ku Society of Investigative Dermatologists mu Meyi 2022.

Wofufuza wamkulu: Prof Iain Chapple ndi Pulofesa wa Periodontology komanso Mtsogoleri wa Sukulu ya Udokotala wa Mano ku yunivesite ya Birmingham UK komanso Mlangizi wa Udokotala Wobwezeretsa Mano.

Amatsogolera gulu lolimba monga gawo la Birmingham's Periodontal Research Group ndipo ndi Director of Research for Institute of Clinical Sciences ku yunivesite ya Birmingham. Iain amayendetsa ntchito zachipatala zapakamwa ndi zachipatala kwa odwala EB akuluakulu mogwirizana ndi Prof Adrian Heagerty, Katswiri wa Dermatologist ndi katswiri wa EB. Iain adalandira mendulo ya Charles Tomes ndi Royal College of Surgeons mu 2012 chifukwa cha kafukufuku wake komanso International Association of Dental Research Distinguished Scientist for Periodontal Research mu 2018.

Ofufuza nawo: Dr Sarah Kuehne, Dr Josefine Hirschfeld, Dr Melissa M Grant ndi Prof Adrian Heagerty

"Ndife okondwa kwambiri ndi thandizo la DEBRA lothandizira ntchitoyi, makamaka chifukwa cha thandizo lamphamvu ndi chidwi kuchokera kwa odwala athu a EB ndi nthumwi pa Sabata la 2019 la mamembala a DEBRA. Izi zitithandiza kuyankha mafunso ofunikira okhudza zomwe mabakiteriya amakhala pakhungu ndikukhala zilonda, komanso momwe angakhudzire momwe chitetezo chathu cha mthupi chimayankhira ndi momwe matuza amachiritsira. Pamapeto pake, tikukhulupirira kuti izi zithandiza mtsogolomo kupanga njira zatsopano zamankhwala. ”

Prof Iain Chapple

Kuti mudziwe zambiri za polojekitiyi, mutha kuwona ulaliki wa Weekend 2018 wa mamembala a DEBRA apa.

Grant Title: Makhalidwe a khungu la microbiome ndi kufufuza ntchito ya neutrophil mu epidermolysis bullosa odwala.

Kodi akufufuzidwa chiyani?
Kafukufukuyu adzafufuza mabakiteriya osiyanasiyana omwe amapezeka pakhungu la anthu omwe ali ndi epidermolysis bullosa (EB). Thupi la munthu lili ndi kuchuluka kwa ma cell a bakiteriya kuwirikiza kawiri poyerekeza ndi maselo amunthu chifukwa chake ndife osakanikirana osakanikirana azinthu zamunthu ndi mabakiteriya, ndipo thanzi limafuna kuti chitetezo chathu cha mthupi chikhale mogwirizana ndi mabakiteriya athu. Ambiri mwa mabakiteriyawa ndi ochezeka. Komabe, mu zilonda za EB, mabakiteriya amatha kusintha ndi kuyambitsa matenda, kuchedwa kuchira, zomwe zimapangitsa kuti zipsera. Pakalipano, mabakiteriya omwe amakhala pakhungu la anthu omwe ali ndi EB sakudziwika bwino. Gululi likukonzekera kufufuza kuti ndi mabakiteriya ati omwe amapezeka pakhungu la anthu omwe ali ndi EB komanso momwe amachitira.

Chifukwa chiyani izi zikufufuzidwa?
Thupi la munthu lili ndi maselo apadera oteteza thupi ku matenda. Ntchito yawo ndi kupeza ndi kuwononga maselo achilendo kapena mabakiteriya omwe angatipangitse kukhala osachiritsika. Mu thanzi, tili ndi mabakiteriya olimbikitsa thanzi, omwe amakhala mosangalala ndi chitetezo chathu cha mthupi, komabe, ngati chilengedwe chikusintha (mwachitsanzo, kuvulala komwe kumayambitsa chithuza), mabakiteriya osiyanasiyana amatha kuyamba kukula ndipo izi zikhoza kusokoneza chitetezo chathu cha mthupi. . M’matenda ena, pamene izi zichitika, maselo a chitetezo cha m’thupi sagwira ntchito monga momwe ayenera kukhalira ndipo amatha kuchita mopambanitsa ndi mabakiteriya ena, m’njira imene imawononganso minofu yathu ndipo ingachedwetse kuchira kwa bala.

Nchifukwa chiyani izi ziri zofunika?
Kafukufukuyu ndi wofunikira pakumvetsetsa ngati maselo a chitetezo chamthupi, otchedwa neutrophils, amagwira ntchito moyenera mu epidermolysis bullosa (EB). Anthu ambiri omwe amakhudzidwa ndi EB nthawi zambiri amadwala matenda osiyanasiyana ndipo izi ndizomwe zikuwonetsa kuti chitetezo chawo cha mthupi sichikugwira ntchito bwino. Kufufuza momwe ma neutrophils amagwirira ntchito kungapereke umboni wopangira njira zamankhwala zomwe zingapangitse kuti athe kuchotsa mabakiteriya osokoneza, kulola kuti mabakiteriya athanzi abwerere ndikukhazikitsanso mgwirizano wofunikira pakati pa mabakiteriya athu "athanzi" ndi chitetezo chathu.
Mbali ziwirizi zidzaphunziridwa chifukwa mu matenda ena amadziwika kuti mabakiteriya ndi mayankho a chitetezo cha mthupi kwa iwo amagwirizana kwambiri. Mabakiteriya ndi maselo a chitetezo cha mthupi amatulutsa zizindikiro zomwe zimakhudza machiritso a khungu, zomwe zingayambitse khungu ndipo zingatipangitse kuti titenge matenda ena. Padzakhalanso zizindikiro kapena mauthenga a "mamolekyu" omwe amathandiza kuchiritsa khungu ndipo kumvetsetsa bwino kwa izi kudzathandizira chitukuko cha mankhwala omwe amaletsa zizindikiro zovulaza koma kuwonjezera zothandiza. Pobweretsa maderawa a kafukufuku palimodzi, tikuyembekeza kupititsa patsogolo chitukuko cha njira zothandizira machiritso kwa anthu omwe ali ndi EB m'tsogolomu.

Kunja kwa khungu kumakhala tizilombo toyambitsa matenda, monga mabakiteriya, bowa, ndi mavairasi, omwe ambiri mwa iwo ndi opanda vuto komanso ochezeka. Komabe, pakakhala zoopsa zomwe zimayambitsa chithuza, tizilombo toyambitsa matenda timeneti timatha kuchita mosiyana, kumayambitsa matenda, kusokoneza machiritso, ndi kupanga zipsera. Thupi la munthu lili ndi maselo apadera a chitetezo cha mthupi omwe amatiteteza ku matenda ndi kutithandiza kulimbana nawo, kuzindikira tizilombo toyambitsa matenda ndi kuwawononga, kotero kuti mabala amatha kuchira.

M'matenda ena, ma cell a chitetezo chamthupi samachita momwe amayenera kukhalira ndipo amatha kuchitapo kanthu mopitilira muyeso ku ma virus ena, zomwe zimayambitsa kuchedwa kwa machiritso a bala ndikuwononga minyewa yathu monga zotsatira zake. Pulojekiti yathu inali ndi cholinga chofuna kudziwa kuti ndi tizilombo ting'onoting'ono timene timakhala pakhungu mu EB, ngati tisintha pakachila, komanso ngati mtundu wina wa chitetezo cha mthupi, neutrophil, umagwira ntchito moyenera mwa anthu omwe ali ndi EB. EB yakhala ikuganiziridwa kuti ndi chikhalidwe chobadwa nacho chomwe chimapangitsa kuti khungu likhale lopweteka kwambiri. Komabe, tikuganiza kuti kuchedwa kuchira kwa zilonda zapakhungu mu EB kungayambitse, mwa zina kuchokera ku maselo ofunika kwambiri a chitetezo cha mthupi sakugwira ntchito bwino.

Kuphunzira kwa tizilombo toyambitsa matenda pakhungu kungakhale kovuta. Choyamba, chifukwa cha kuchepa kwa tizilombo toyambitsa matenda pakhungu, ndizovuta mwaukadaulo kuwayesa kuti afufuze. Kachiwiri, magulu a tizilombo amasintha m'thupi lonse: mawonekedwe a khungu la microbiome m'manja ndi osiyana ndi mapazi. Chifukwa chake, tidayenera kutsimikiza kuti tagwiritsa ntchito njira yoyenera yotsatsira, monga thonje swabs, ndipo tinatha kuzindikira tizilombo toyambitsa matenda, tisanatenge zitsanzo kuchokera kwa odwala EB.

Titatsimikizira kuti njira zathu zagwira ntchito, tidapereka zida zotsuka ndikufunsa anthu omwe ali ndi EB komanso opanda EB kuti atenge zotupa pakhungu pakapangidwa matuza kuti athe kusamutsa ma virus pakhungu lawo kupita ku swab. Poyang'ana DNA, yomwe imagwira ntchito ngati barcode, tinatha kunena zamoyo zomwe zinalipo komanso zomwe zinkachita.

Sitinangoyang'ana pakhungu losakhudzidwa, koma tawonanso kusiyana kwa khungu la matuza, ndi momwe maderawa amasinthira pochira mabala. Tapeza kuti khungu la odwala EB liri ndi tizilombo toyambitsa matenda a gulu linalake lotchedwa "bacillales", komanso kuti gulu ili linali lachindunji pa EB iliyonse. Tidawonanso kusiyana kwa bowa omwe amakhala pakhungu la anthu omwe ali ndi EB komanso momwe izi zimasinthira pakuchiritsa mabala.

Chinthu china chofunika kwambiri cha polojekiti yathu ndikumvetsetsa zomwe zimachitika m'matuza ndi momwe chitetezo cha mthupi cha anthu omwe ali ndi EB amachitira ndi tizilombo toyambitsa matenda. Tinapempha anthu odzipereka kuti atole madzi kuchokera ku matuza ndipo tinasanthula madzi a chithuza kuti tifufuze ndi kuwerengera mapuloteni omwe amapezeka mwa iwo. Tawonetsa kuti pali kusiyana kothekera kwa mapuloteniwa omwe angatiuze za momwe matuza amapangidwira kapena kuchira. Mwachindunji, tidazindikira puloteni yofunikira yomwe sinapezeke mwa anthu omwe ali ndi EB koma idapezeka mwa anthu opanda vutoli. Tsopano tikufuna kumvetsetsa ntchito ya puloteniyi komanso ngati ingakhale cholinga cha chithandizo chamankhwala chatsopano. Tidazindikiranso masiginecha a mapuloteni amitundu yonse yosiyanasiyana yamadzimadzi omwe amawunikidwa, kutilola kufotokoza kusiyana pakati pa ma subtypes a EB.

Tinaona kusiyana kwa khalidwe la neutrophils, mtundu winawake wa maselo oteteza thupi amene amapezeka m’magazi. Maselo amenewa ndi omwe amayamba kuyankha pa nthawi ya matenda ndi machiritso a mabala, ndipo tinawona momwe iwo amachitira ndi kukhudzidwa kwa mabakiteriya kwa odwala omwe ali ndi EB. Tinapeza mayankho okulirapo a neutrophil, makamaka mwa anthu omwe akhudzidwa ndi EB yolumikizana ndi anthu omwe alibe vutoli. Mchitidwe wokokomezawu umagwirizanitsidwa ndi kuwonongeka kwa minofu mwa wolandirayo ndipo ukhoza kufotokozera kapena kuthandizira kuchepetsa kuchira kwa bala. Izi zitha kuchepetsedwa ndi zinthu zachilengedwe zomwe zimalepheretsa kuwonongeka kotere, zomwe zitha kuyimira njira ina yatsopano yothandizira.

Kutenga pamodzi zomwe tapeza zavumbula kuti tizilombo toyambitsa matenda timakhala bwanji pakhungu la odwala EB, momwe amasinthira panthawi ya machiritso, komanso momwe thupi limayankhira mabakiteriya. Chifukwa cha chidziwitso chatsopanochi, zitha kukhala zotheka kupanga njira zochiritsira zatsopano kapena zopaka mabala pogwiritsa ntchito pre- ndi probiotics ndi/kapena antioxidant micronutrients, kapena m'malo mwa mapuloteni kuti abwezeretse khungu lathanzi komanso logwira ntchito bwino lamaluwa, kuchepetsa chiopsezo cha matenda mwa anthu omwe amakhala nawo. EB ndikuthandizira kuchiritsa mabala. (Kuchokera ku lipoti lomaliza la 2023.)

• Mliri utangochepetsedwa, kulembetsa kwa odwala omwe ali ndi EB kunapita patsogolo mpaka kutha.
• Zosintha zomwe zingakhudze ndi kukhudza kuchotsedwa kwa DNA kwa EB microbiome zinadziwika ndikuyesedwa ndipo ndondomeko yoyenera yowunikira odwala a EB inafotokozedwa.
• Protocol yofotokozedwayo idagwiritsidwa ntchito kusonkhanitsa ndi kuchotsa zitsanzo 94 za swab.
• Zitsanzo za 44 zidachitidwa motsatizana ndi kusanthula kwa bioinformamatic. Kusanthula pang'ono kwa izi kunawonetsa kusiyana pakati pa ma microbiome a anthu omwe akhudzidwa ndi EB kapena dystrophic EB ndi anthu athanzi.
• Masamba amthupi amayenera kuganiziridwa kuti athe kuzindikira kwathunthu pakhungu la microbiome mu EB.
• Zitsanzo zotsalazo zidakonzedwa bwino ndikutsatidwa ndipo pano zikuwunikiridwa ndi bioinformatics.
• Tasanthula zitsanzo 16 zamadzimadzi zamadzimadzi zomwe zili ndi cytokine komanso zochita za protease.

Pakhungu la munthu mumakhala tizilombo toyambitsa matenda monga mabakiteriya, bowa, ndi mavairasi, omwe ambiri mwa iwo ndi opanda vuto komanso ochezeka. Komabe, pakakhala zoopsa zomwe zimabweretsa chithupsa pakhungu, tizilombo toyambitsa matenda timeneti titha kuchita mosiyana, kumayambitsa matenda, kusokoneza machiritso a chilonda, ndi kupanga zipsera.

Thupi la munthu lili ndi maselo apadera a chitetezo cha mthupi omwe amatiteteza ku matenda ndi kutithandiza kulimbana nawo, kuzindikira tizilombo toyambitsa matenda ndi kuwawononga. M'matenda ena, ma cell a chitetezo chamthupi samachita momwe amayenera kukhalira ndipo amatha kuchitapo kanthu mopitilira muyeso ku ma virus ena, zomwe zimayambitsa kuchedwa kwa machiritso a bala ndikuwononga minyewa yathu monga zotsatira zake.

Pulojekiti yathu ikufuna kudziwa kuti ndi tizilombo ting'onoting'ono timene timakhala pakhungu mu EB, kaya mtundu wina wa chitetezo cha mthupi, neutrophil, umagwira ntchito moyenera mwa anthu omwe ali ndi EB, komanso momwe mapuloteni opezeka m'matuza amasinthira mu EB.

Mu kafukufuku yemwe adanenedwa, takonza njira yoyang'ana ma virus omwe amakhala pakhungu ndipo tawagwiritsa ntchito kusonkhanitsa ma swabs a khungu kuchokera kwa anthu omwe alibe EB. Tidapereka zida zotsuka ndikufunsa anthu kuti atenge zinsalu zapakhungu pakapangidwa matuza kuti athe kusamutsa ma virus pakhungu lawo kupita ku swab. Poyang'ana DNA, yomwe imagwira ntchito ngati barcode, tidzatha kunena zamoyo zomwe zilipo komanso zomwe zikuchita.

Tili ndi zitsanzo za 94 zomwe zimayenera kufufuzidwa, ndipo ife tiri oposa theka la kusanthula kwautali ndi kovuta. Kuyang'ana koyamba mu data, tawona kuti anthu omwe akhudzidwa ndi dystrophic EB ali ndi ma microbiome osiyana ndi omwe alibe vutoli. Makamaka, gulu la mabakiteriya, proteobacteria, ndilochuluka kwambiri mwa anthu omwe ali ndi khungu. Tidawona momwemonso anthu omwe akhudzidwa ndi ma junctional EB. Poyang'ana mwatsatanetsatane zamoyo zomwe zimakhala pakhungu la anthu omwe akhudzidwa ndi JEB, tidawunikiranso kufunikira koganizira malo omwe matuzawo adapanga. M'malo mwake, microbiome ya bondo imawoneka yosiyana kwambiri ndi mkono, ngakhale mwa anthu opanda EB. Chifukwa chake, ndikofunikira kufananiza zitsanzo kuchokera patsamba lomwelo.

Pamene tikupitiriza kusanthula kwathu, tidzakhala ndi chidziwitso chochuluka cha microbiome ya anthu omwe ali ndi EB, ndipo tidzatha kuzindikira ntchito zomwe mabakiteriya angathe kuchita komanso zomwe tingathe kupeza njira zochiritsira zatsopano.

Kuonjezera apo, tafufuza mapuloteni omwe amapezeka m'matuza a odwala omwe ali ndi EB. Tawonetsa kuti pali kusiyana kothekera kwa mapuloteniwa omwe angatiuze momwe matuza amapangidwira kapena kuchiritsa. Ntchito yowonjezereka ikupitilira kufufuza izi. (Kuchokera ku lipoti la 2022).