Ma `lumot

Inson mikrobiomasining buzilishi qancha kasalliklar bilan bog'liq bo'lishi mumkin?


Men radioga ro'yxat berayotgan edim va yaqinda o'tkazilgan tadqiqotlar mikrobiomada ba'zi bakteriyalar etishmayotganda bolalar va astmaning yuqori holatlari o'rtasida bog'liqlik borligini eshitdim. Buzilgan mikrobioma bilan qancha boshqa kasalliklar bog'lanishi mumkin va etishmayotgan bakteriyalarni ko'paytirish yo'llari bormi?


Bu ochiq savol va faol tadqiqot sohasi. Raqam haqidagi savolingizga aniq javob topa olmaysiz, chunki har bir yangi kashfiyot umumiy songa qo'shiladi.

Ko'paytirishga kelsak, biz hatto bizni to'ldiradigan mikroblarning barcha shtammlarini ham aniqlamadik, ko'plarini in vitroda etishtirish juda qiyin va biz har bir tur uchun barcha funktsiyalarni bilmaymiz, shuning uchun bizda aniq tasavvur yo'q. u erda bo'lishi kerak bo'lgan, yo'qmi va ba'zi turlar bizga foyda keltirishi uchun birgalikda ishlaydimi yoki yo'qmi. Irritabiy ichak sindromi kabi ba'zi holatlar uchun najas transplantatsiyasi sinab ko'rilgan davolash usullaridan biridir.

Oxirgi sharhlar uchun adabiyotlarni qidiring. Tabiat sharhlari, ayniqsa, inson mikrobiomasi kabi yangiliklar kabi mavzularda batafsil sharhlar qiladi. Bu, ehtimol, boshlash uchun eng yaxshi birinchi joy. Shundan so'ng siz sharhda keltirilgan ma'lumotnomalarni o'rganishni boshlashingiz mumkin. Bu sizga odatda maydonda yaxshi o'yin holatini beradi.


Bizdagi mikroblar va ularning inson salomatligi va kasalliklaridagi roli

Odamlar va ularning mikrobiomalari haqidagi eng keng qamrovli tahlilning yakuniy natijalari mikroblar va mikrobiomalarning sog'liq muammolari bilan bog'liqligini aniqlaydi.

Sizning tanangizda kuchli, ammo ko'rinmas mikroblar shohligi mavjud. Kichik, ammo nihoyatda kuchli, bu minglab turlar va trillionlab aholi tanangizning barcha qismlarida yashaydi va turli xil inson mikrobiomasini tashkil qiladi. Ushbu mikrobiomalar sog'lig'ingizni qo'llab-quvvatlaydi va saqlaydi, shuningdek, mikrobioma qandaydir tarzda buzilganida, saraton, otoimmün va yurak-qon tomir kasalliklari kabi yuzlab kasalliklar bilan bog'liq.

Shuning uchun inson mikrobiomasi salomatlik tadqiqotining muhim yo'li ekanligi ajablanarli emas. Bu bizning sog'lig'imiz uchun juda muhim ahamiyatga ega, chunki yaqinda nashr etilgan maqolalar soni Tabiat Inson mikrobiomi loyihasining ikkinchi bosqichidan boshlab.

Kim bor? Odamlarda mikrobiomani o'rganish

Milliy Sog'liqni Saqlash Institutlari (NIH) Umumiy Jamg'armasi 2007 yilda o'n yillik inson mikrobiomasi loyihasini (HMP) tashkil etdi. HMP loyihasi o'sha paytda yosh soha bo'lgan tadqiqotni galvanizatsiya qilish uchun jamoat resursi bo'lishi uchun mo'ljallangan. Asosiy maqsad ma'lum kasalliklar va populyatsiyalarda mikrobiomani o'rganish imkoniyatiga ega bo'lish uchun katta tadqiqot hamjamiyatiga ma'lumotlar to'plami va analitik va klinik protokollar bilan asboblar qutisini yaratish edi.

Loyihaning birinchi bosqichida 300 ta sog'lom odamdan olingan namunalar yordamida tananing beshta maxsus hududi: teri, og'iz bo'shlig'i, nafas yo'llari, oshqozon-ichak va urogenital yo'llar bilan bog'liq bo'lgan mikroblar (shu jumladan, bakteriyalar, zamburug'lar va viruslar) turlari bo'yicha ma'lumot to'plami kataloglangan. kattalar erkaklar va ayollar.

Ular ushbu mikrobial jamoalarni tahlil qilish uchun Inson genomi loyihasi davomida birinchi ishlab chiqilganlardan moslashtirilgan DNK ketma-ketlik texnologiyalaridan foydalanganlar. Mikrobioma bilan bog'liq kasalliklar odatda yuqumli emas, lekin inson mikrobiomasi bilan izohlanishi mumkin bo'lgan nisbatga ega.

Tadqiqotchilar ma'lumotnoma ma'lumotlar to'plamidan bunday yuqumli bo'lmagan kasalliklar yoki sharoitlar bilan bog'liq bo'lishi mumkin bo'lgan mikrobial hamjamiyat farqlarini aniqlash uchun yo'l xaritasi sifatida foydalanganlar.

Bu erda muhim ogohlantirish bor.

Tadqiqotchilar hali mikroblar jamoasidagi o'zgarish kasallikka olib keladimi yoki mikroblar jamoasi kasallikning rivojlanishiga javoban o'zgaradimi yoki yo'qligini bilishmaydi.

Tadqiqotchilar hali mikroblar jamoasidagi o'zgarish kasallikka olib keladimi yoki mikroblar jamoasi kasallikning rivojlanishiga javoban o'zgaradimi yoki yo'qligini bilishmaydi.

Ilgari HMP tadqiqotlarida mikrobioma o'lchovlarining surati olingan bo'lsa-da, agar bunday tadqiqotlar mikrobiomaning kasallik bilan sabab-ta'sir munosabatlarini aniqlashni boshlasa, bu jamoalar vaqt o'tishi bilan qanday o'zgarishini tushunish kerak edi. Bu, ayniqsa, muhim ahamiyatga ega, chunki inson organizmidagi mikrob populyatsiyasi inson hayoti davomida o'zgaradi va ovqatlanish, stress va boshqa atrof-muhit omillariga ta'sir qiladi.

Tadqiqotchilar, aslida, mikrobioma va inson tanasi haqida video yaratishlari kerak edi.

Ular nima qilishyapti? Odamlar va mikroblarning o'zaro ta'siri

NIH Umumiy fondi 2014-yilda inson mikrobiomasining integratsiyaviy loyihasini (iHMP) ikkinchi bosqichni boshladi. Ushbu bosqich RNK, oqsillar va mikrobiomadan metabolitlar deb ataladigan metabolizm bilan bog'liq moddalar kabi biomolekulalarni o'lchash va tahlil qilish usullarini ishlab chiqish uchun mo'ljallangan edi. inson uy egasi.

Tadqiqotchilar ushbu usullarni uchta model mikrobioma bilan bog'liq sharoitlarni o'rganish uchun qo'llashdi: erta tug'ilish, yallig'lanishli ichak kasalligi (IBD) va prediabet. Maqsad, qaysi biologik xususiyatlar yoki xususiyatlar to'plami ushbu shartlar haqida tushunchaga ega bo'lish uchun eng foydali ekanligi isbotlanganligini baholash edi.

Tadqiqotchilar uzoq vaqt davomida har bir shart uchun sog'lom va ta'sirlangan shaxslarning mikrobiomasini o'rganishdi.

“Biz inson tanasidagi mikrob turlarini inventarizatsiya qilishni yakunladik. Ammo mikroblar bir-biri bilan va uy egasi bilan o'zaro ta'sir qiladi. Ularning har biri bir-biriga ta’sir qilishi mumkin”, dedi Lita Proktor, inson mikrobiomasi loyihasining dastur direktori. "Shunday qilib, biz mikrobioma va uy egasi o'rtasidagi vaqtga sezgir o'zaro ta'sirlarni qo'lga kiritishimiz muhim edi."

Erta tug'ilish va vaginal mikrobiomada etishmayotgan bakteriyalar

Erta tug'ilish, ya'ni ayollar homiladorlikning 37 xaftasidan oldin tug'ilish holati, dunyo bo'ylab neonatal o'limning ikkinchi eng keng tarqalgan sababidir. Erta tug'ilish holatlari ham aholi tomonidan sezilarli darajada farq qiladi. Kasalliklarni nazorat qilish va oldini olish markazlarining ma'lumotlariga ko'ra, 2016 yilda afro-amerikalik ayollar o'rtasida erta tug'ilish darajasi oq tanli ayollarga nisbatan 14 foizni, 9 foizni tashkil etdi - bu deyarli 50 foiz farq.

Homilador ayolning sog'lom vaginal mikrobiomasi chaqaloqning sog'lom tug'ilishi bilan chambarchas bog'liq bo'lganligi sababli, iHMP ning birinchi model tizimi, Vaginal Mikrobiome Konsortsiumi Multi-Omik Mikrobioma Tadqiqoti: Homiladorlik tashabbusi (MOMS-PI) homilador ayolning vaginal mikrobiomalarini tavsiflashga harakat qildi. ayollar erta tug'ilish xavfini o'lchash uchun, ayniqsa afro-amerikalik ayollarga e'tibor berish.

Loyiha homilador ayollar guruhini ro'yxatga oldi va kuzatib bordi, ularda jami 45 ta erta tug'ilgan va 90 ta to'liq tug'ilgan. Mikrobioma ma'lumotlarini, shuningdek, mikrobioma va sub'ektlarning gen ifodasi, oqsil va metabolitlar darajasini o'z ichiga olgan boshqa xususiyatlarni ko'rib chiqib, tadqiqotchilar hayratlanarli narsaga duch kelishdi.

Bir tadqiqot natijalarida tadqiqotchilar asoratlanmagan homiladorlikdagi vaginal mikrobiomalarning normal rivojlanishini erta tug'ilgan ayollardagi bilan solishtirishdi. Ular homiladorlikning dastlabki bosqichlarida erta tug'ilishni boshdan kechirgan ayollarda (asosan afro-amerikalik) tabiiy bakteriya darajasi sezilarli darajada past ekanligini aniqladilar. Lactobacillus crispatus. Bu sog'lom vaginal muhitni saqlash uchun muhim bo'lgan mikrobiomaning asosiy a'zosidir.

Biroq, birinchi trimestrning oxiriga kelib, bu ayollarning vaginal mikrobiomalari normal holatga qaytishga moyil edi. Laktobakteriyalar- hukmron jamiyat. Tadqiqotchilar endi bu mikrobning homiladorlikning dastlabki kunlarida onaning vaginasidan nima uchun samarali tarzda yo'qolib ketishini bilishni istaydilar.

Bu natija, shuningdek, tadqiqotchilarga homiladorlikning erta davridagi ayolning mikrobial jamoa tarkibini o'rganish erta tug'ilish xavfini bashorat qilishda eng foydali bo'lishi mumkinligini tasdiqladi.

Erta tug'ilish xavfini bashorat qilishda homiladorlikning erta davrida emas, balki keyinroq ayolning mikrobial jamoa tarkibini o'rganish foydali bo'lishi mumkin.

"Bu natijalar, ayniqsa, quvonarli va dastlab kutilmagan edi, chunki ular bizga erta tug'ilish uchun biomarkerlarni homiladorlikning boshida aniqlash osonroq bo'lishi mumkinligini taklif qilmoqdalar", dedi Gregori Bak, tadqiqotning katta tadqiqotchisi va Virjiniya Hamdo'stlik universiteti professori. . "Bizning bashoratli modelimiz sezgirlik va o'ziga xoslikka ega, hozirda qo'llanilayotgan klinik ko'rsatkichlardan biroz yaxshiroq."

Agar bu natijalar afro-amerikalik ayollar bilan boshqa klinik sinovlarda takrorlansa, ular shifokorlarni mikrobiomaga asoslangan biologik belgilar bilan ta'minlashi mumkin, bu esa ayolning homiladorlik davrida erta tug'ilishni bashorat qilishi mumkin va shuning uchun erta tug'ilishning oldini olish uchun aralashuvlar uchun ko'proq vaqt va imkoniyat beradi.

Yallig'lanishli ichak kasalligi va o'ziga xos mikrobial mahsulotlarni yo'qotish

Odatda ko'p yog'li, kam tolali parhez va antibiotiklardan tez-tez foydalanish sifatida tavsiflangan "G'arbiy dieta" deb ataladigan narsa ichak mikrobiomasi tarkibining sog'lomdan o'zgarishi bilan bog'liq. Bu o'zgarishlar, o'z navbatida, yallig'lanishli ichak kasalliklari (IBD) va IBD pastki turlari Kron kasalligi va yarali kolitning ko'payishi bilan chambarchas bog'liq. Ikkalasi ham isitma, ishtahani yo'qotish va charchoq bilan ajralib turadigan og'riqli holatlardir va AQShda 3 milliondan ortiq odamga ta'sir qiladi.

IBDdagi mikrobiomaning roli va mikrobioma kasallikning rivojlanishiga qanday ta'sir qilishi haqida kam ma'lumot mavjud. Hozirgacha.

Garvard sog'liqni saqlash maktabi doktori Kertis Xuttenxauer, Massachusets umumiy kasalxonasida doktor Ramnik Xavier va iHMPning ikkinchi namunaviy tizimi - Yallig'lanishli ichak kasalliklari multi-omiks (IBDMBD) loyihasining boshqa a'zolari tomonidan taqdim etilgan. IBDdagi mikroblar jamoasining eng to'liq tavsifi.

Ular Kron kasalligi va yarali kolit bilan og'rigan, yallig'lanish darajasi past bo'lgan yoki to'liq rivojlangan kasalligi bo'lgan bemorlarni jalb qilishdi. Bir yuz o'ttiz ikki bemor bir yil davomida o'rganildi va har biri uchun tadqiqotchilar tadqiqot boshida ichak biopsiyalarini olishdi, har ikki haftada najas namunalarini yig'ishdi va har to'rt oyda bu sub'ektlardan qon namunalarini olishdi.

Erta tadqiqotga o'xshab, tadqiqotchilar ushbu namunalarni mikrobioma tarkibi, shuningdek, oqsillar, metabolitlar va boshqa biologik xususiyatlar uchun tahlil qilishdi. Ushbu ma'lumotlar bilan tadqiqotchilar vaqt o'tishi bilan mikrobioma va kasallik holatining o'zaro ta'sirini o'rganishga muvaffaq bo'lishdi.

Ko'pgina hollarda, IBD bemorlarining mikrobiomasi bir necha hafta davomida bo'yanishda butunlay o'zgargan. Bunday dramatik o'zgarish IBD bo'lmagan ishtirokchilarda kamdan-kam uchraydi.

Ko'pgina hollarda, IBD bemorlarining mikrobiomasi bir necha hafta davomida bo'yanishda butunlay o'zgargan.

Ushbu tadqiqotchilar sog'lom ichak mikrobiomalarida ko'p miqdorda topilgan mikroblar, masalan, F. prausnitzii va R. hominis, IBD bemorlarida kamaydi. E. coli, sog'lom ichak mikrobiomalarida ham uchraydigan, lekin odatda juda past darajada bo'lgan boshqa bakteriya IBD bemorlarida ko'paygan.

Ichaklarimizdagi bakteriyalar dietamizni buzish uchun zarurdir. Ushbu parchalanish jarayonida bakteriyalar birikmalar hosil qiladi, ularning ko'plari mikrobioma va inson uy egasi o'rtasida aloqa signallari bo'lib xizmat qiladi. Shuning uchun bu bakteriyalarni yo'qotish bu muhim signal molekulalarini kamaytirishi mumkin.

Ushbu tadqiqot ichakdagi butirat darajasining sezilarli darajada pasayishini aniqladi, bu yallig'lanishni kamaytiradigan va ichak shilliq qavatini mustahkamlaydigan ichak bakteriyalari tomonidan ishlab chiqarilgan signalizatsiya molekulasi. Tadqiqotchilar butiratning kamayishi mikroblarning sezilarli darajada kamayishi bilan bog'liq bo'lishi mumkinligini taxmin qilishadi F. prausnitzii va R. hominis, bu ichak mikrobiomasida asosiy butirat ishlab chiqaruvchilari bo'lishi mumkin.

"Har bir insonning mikrobiomasi va immun tizimi aniq, muvofiqlashtirilgan tarzda javob berdi. Bu kasallikka olib keladigan murakkab o'zaro bog'liqliklarni ajratishni qiyinlashtirsa-da, bu bizni bu kiruvchi aloqa zanjirlarini buzish uchun yangi imkoniyatlarga ishora qiladi va bu yangi usullarga olib keladi. IBDni davolash yoki boshqarish uchun ", dedi Xuttenxauer.

Oldindan ish tashlash: 2-toifa diabetning dastlabki bosqichida

2-toifa diabet (T2D) dunyoda epik nisbatlarga yaqinlashmoqda va semirib ketish epidemiyasi bilan chambarchas bog'liq. AQShning kattalar aholisining 10 foizi T2Dga ega, yana 30 foizi prediabetga moyil. Prediabet - bu odamning qondagi qand miqdori ko'tarilgan, ammo T2D tashxisini qo'yish uchun etarli darajada yuqori bo'lmagan sog'liq holati. Buning sababi shundaki, ham prediabet, ham T2D odamlar odatda insulin qarshiligidan aziyat chekishadi, bu erda organizm glyukozani qon oqimidan va hujayralarga o'tkazish uchun gormonning signallariga javob bermaydi. Prediyabetik aholining deyarli 70% hayoti davomida diabetga chalinadi.

iHMP ning uchinchi model tizimi, Stenford universiteti fanlari doktori Maykl Snayder va Jekson genomik tibbiyot laboratoriyasi doktori Jorj Vaynstok boshchiligidagi Integratsiyalashgan Shaxsiy Omiks Loyihasi (IPOP) fundamental savollarga javob berish uchun yaratilgan. Masalan: prediabetning T2D ga o'tishiga nima sabab bo'ladi? Prediabet holatida qanday stress omillari bunday siljish xavfini oshiradi?

IPOP tadqiqotida to'rt yil davomida o'rganilgan 106 nafar sog'lom va diabetga chalingan odamlar jalb qilindi. To'rt yil davomida ularning ichak va burun mikrobiomalari, shuningdek, xost va mikrobiomaning biologik omillari kuzatildi.

Boshlash uchun tadqiqotchilar sog'lom ishtirokchilarning ichak mikrobiomalari prediabet belgilari bo'lganlarga qaraganda boshqacha ekanligini aniqladilar va shu bilan bu prediabetli bemorlarda mikrobioma kamaygan yoki nosog'lom bo'lishi mumkin.

Bundan tashqari, sog'lom va diabetga chalinganlarning bir qismi respirator virusli infektsiyani boshdan kechirdi, bu davrda tadqiqotchilar ikkalasini ham grippga qarshi emlash bilan immunizatsiya qildilar.

Odatda odamda respirator virusli infektsiyalar bo'lsa, uning immuniteti infektsiyaga qarshi kurashish uchun faollashadi. Qizig'i shundaki, tadqiqot shuni ko'rsatdiki, respirator virusli infektsiyaga chalingan prediabetli ishtirokchilar immunizatsiya qilinganida, ularning immun tizimi sog'lom ishtirokchilarga nisbatan sekin javob beradi, ammo baribir samarali. 2-toifa diabet immunitet tizimi bilan bog'liq stresslar bilan bog'liq bo'lganligi sababli, tadqiqotchilar immunizatsiya prediabetli bemorlarni kasallikning to'liq boshlanishidan himoya qilishi mumkinligini taxmin qilishdi.

Emlash prediabetga chalingan bemorlarni kasallikning to'liq boshlanishidan himoya qilishi mumkin.

"Insulinga chidamli bo'lgan odamlar sog'lom bo'lgan davrda ham bir nechta mikrobial farqlar bilan farq qilganini ko'rish ajoyibdir", dedi Snayder.

Prediyabetik bemorlarda o'zgargan mikrobioma borligini ko'rsatadigan dalillar mavjud, bu ham zaiflashgan immunitet tizimi bilan bog'liq. Prediyabetik bemorlar immunitet tizimini mustahkamlash uchun immunizatsiyadan foyda ko'rishlari mumkin, bu ularni T2D rivojlanishidan himoya qiladi. Faqat kattaroq tadqiqotlar bu farazni tasdiqlashi mumkin.

Kelajak tushunchalari

iHMP mikrobioma bilan bog'liq uchta sharoitda vaqt o'tishi bilan inson tanasi va uning mikrobiomasidan kelib chiqqan mikroblar hamjamiyati tarkibi va gen ekspressiyasi, oqsillar, metabolitlar va immun tizimining xususiyatlari haqida biologik ma'lumotlarning eng katta to'plamini yaratdi.

Inson tanasi va uning mikrobiomasidagi biologik xususiyatlarni kuzatish orqali iHMP loyihalari ma'lum mikroblar va ularning xususiyatlarining yo'qolishi yoki ortishi odamlarda erta tug'ilish, IBD va prediabet holati bilan chambarchas bog'liqligini aniqladi.

Ba'zi hollarda bu omillar kasallikning dastlabki ko'rsatkichlari bo'lib xizmat qilgan va shuning uchun bashorat qiluvchi biomarkerlarning kelajakdagi rivojlanishi uchun va'da beradi.

Ushbu uchta modeldagi mikrobioma sharoitida to'plangan ma'lumotlar to'plami katta jamoa uchun qaysi biologik omillar o'zlarining maxsus tadqiqotlarida eng chuqurroq bo'lishini sinab ko'rish uchun manba bo'lib xizmat qiladi. Ushbu tadqiqotlardan olingan ma'lumotlar HMP ma'lumotlarini muvofiqlashtirish markazi tomonidan arxivlangan va tuzatilgan va kengroq hamjamiyat tomonidan keyingi tadqiqotlar uchun cheklanmagan foydalanish uchun mavjud.


KIRISH

Inson mikrobiomasi tanamizda va tanamizda yashaydigan bakteriyalar, arxeyalar, viruslar va eukaryotik mikroblardan iborat. Ushbu mikroblar bizning fiziologiyamizga salomatlik va kasalliklarda ta'sir qilish uchun ulkan salohiyatga ega. Ular metabolik funktsiyalarga hissa qo'shadi, patogenlardan himoya qiladi, immunitet tizimini tarbiyalaydi va bu asosiy funktsiyalar orqali bizning fiziologik funktsiyalarimizning ko'pchiligiga bevosita yoki bilvosita ta'sir qiladi.

Inson mikrobiomasini o'rganish madaniyatga bog'liq bo'lmagan tahlillarni o'tkazish uchun texnologik yutuqlar bilan davom ettirildi (1). Ko'pgina tadqiqotlarda mikrob populyatsiyasining bakterial tarkibiy qismlari 16S rRNK-kodlovchi gen (bundan buyon matnda 16S) sekvensiyasi, so'ngra ma'lum bakterial ketma-ketlik ma'lumotlar bazalari bilan taqqoslash yo'li bilan aniqlanadi. Murakkab jamoadagi barcha mikrob DNKlarini ketma-ketlashtirish orqali metagenomik tahlil mikrob populyatsiyasining genetik salohiyatini baholashning qo'shimcha afzalligiga ega. Mikrobial transkriptom, proteom va metabolomni tahlil qilish uchun boshqa metodologiyalar mikrobial fiziologiyaning keyingi darajalarida qo'shimcha ma'lumot beradi (2). Biz ushbu sohadagi aniq texnik mulohazalarni batafsil ko'rib chiqmaymiz, ammo qiziqqan o'quvchilar uchun so'nggi sharh maqolalariga murojaat qilinadi (3-5).

So'nggi paytlarda mikrobioma tuzilishini tavsiflashda katta muvaffaqiyat mikrobiota va xost o'rtasidagi funktsional o'zaro ta'sirlar bo'yicha davom etayotgan va kelajakdagi tadqiqotlar uchun yo'l ochdi. Mikrobiotaning funktsiyasini o'rganish inson gomeostazasi va kasallik patogenezida mikrobiotaning rolini tushunish uchun juda muhim bo'ladi. Ushbu sharhda biz sog'lom holat va muayyan kasallik holatlari bilan bog'liq mikrobiomaning tuzilishi va funktsiyasi haqidagi tushunchamizdagi so'nggi yutuqlarni muhokama qilamiz.

Inson mikrobiomasi to'g'risidagi ma'lumotlarning to'planishi

So'nggi yillarda inson mikrobiomasi to'g'risida to'plangan ma'lumotlarning ulkan kengayishi inson mikrobiomasini tavsiflash bo'yicha bir qancha keng ko'lamli sa'y-harakatlar natijasida yaratilgan ma'lumotlar, xususan, Inson ichak traktining Evropa metagenomikasi (MetaHIT) va NIH tomonidan moliyalashtirilgan Inson mikrobiomasi loyihasi tomonidan ta'kidlangan. (HMP) (6, 7). 2010 yilda MetaHIT konsortsiumining dastlabki tadqiqotida 3,3 million ortiqcha bo'lmagan najas mikrobial genlar ketma-ketligi qayd etilgan, bu avvalgi barcha tadqiqotlarda qayd etilgan mikrobial DNK ketma-ketliklarining deyarli 200 baravar ko'pligini ifodalaydi (7). 2014 yil iyul oyida 1070 ta odamning 1267 ta ichak metagenomlaridan olingan metagonomik ketma-ketlik ma'lumotlarining birlashtirilgan to'plami, shu jumladan MetaHIT'dan 760 ta Yevropa namunalari, HMP'dan 139 ta Amerika namunalari va katta diabet tadqiqotidan olingan 368 ta Xitoy namunalari ortiqcha bo'lmagan genlar katalogi bilan nashr etildi. 9,8 million mikrob genlari (*8). Har bir namunada 750 000 ga yaqin gen yoki inson genomidagi genlar sonidan taxminan 30 baravar ko'p bo'lgan va 300 000 dan kam genlar odamlarning 50% dan ko'prog'i tomonidan taqsimlangan. Ushbu so'nggi tadqiqotda aniqlangan yangi genlarning aksariyati nisbatan kam bo'lib, odamlarning 1% dan kamrog'ida topilgan. Ushbu to'plamda ko'pchilik inson ichak bakteriyalari uchun deyarli to'liq genlar to'plami mavjud deb taxmin qilinadi va inson mikrobiomasining miqdori va o'zgaruvchanligini ko'rsatadi.

Sog'lom kattalar mikrobiotasining tuzilishi va dinamikasi

Sog'lom odamlarda mikrobiomaning tavsifi mikrobiomaning salomatlik va kasallikka hissa qo'shishdagi rolini tushunishda muhim dastlabki qadamdir. Sog'lom voyaga etgan odamlarning har biri odatda nisbatan kam ma'lum bo'lgan bakterial filalarga tegishli bo'lgan 1000 dan ortiq turdagi bakteriyalarni o'z ichiga oladi, bunda Bacteroidetes va Firmicutes dominant fila hisoblanadi (9). Ichak mikrobiotasi tananing boshqa joylariga nisbatan ancha xilma-xildir (1-jadval) va sog'lom ko'rinadigan odamlar orasida ichak mikrobiotasi tarkibiy qismlarida sezilarli o'zgarishlar mavjud (10). Sog'lom odamlar orasida mikrobial o'zgaruvchanlikni hisobga olish usuli sifatida tadqiqotchilar inson populyatsiyasidagi mikrob populyatsiyasining ma'lum barqaror naqshlarini aniqlashga harakat qilishdi (11). HMP ma'lumotlari ko'plab bakterial taksonlar konfiguratsiyasining statistik tahlili asosida tananing turli joylarida jamoa turlarini aniqlash uchun ishlatilgan (*12). Najasda to'rtta alohida jamoalar topilgan va jamiyat turlari bilan bog'liq metadata omillari emizish, jins va ta'limni o'z ichiga olgan. Qizig'i shundaki, og'iz bo'shlig'idagi jamoa turlari najasdagilarni bashorat qilgan, ammo o'ziga xos tarkibiy qismlar boshqacha bo'lgan. Antibiotiklarni qabul qilmaydigan 37 nafar sog'lom amerikalik kattalar ishtirokidagi yaqinda o'tkazilgan tadqiqotda, odamdagi najasli bakteriya turlarining 70% dan ko'prog'i 1 yil davomida barqaror bo'lgan va 5 yil ichida bir nechta qo'shimcha o'zgarishlar o'lchangan (*13). Hisob-kitoblar shuni ko'rsatdiki, turlar o'nlab yillar davomida barqaror bo'lishi mumkin, agar shaxsning butun umri davomida bo'lmasa, bu kattalar oila a'zolari bilan bo'lingan, ammo qarindosh bo'lmagan shaxslar bilan bo'lmagan turlardan dalolat beradi. Biz sog'lom odamlarda mikrobiomaning tuzilishi va dinamikasi haqida chuqur tushunchaga ega bo'lgan bo'lsak-da, bu harakat populyatsiyadagi sezilarli o'zgaruvchanlik, vaqt o'tishi bilan individual o'zgaruvchanlik va mikrobiotani tavsiflashning eng mazmunli usullari bo'yicha noaniqlik bilan murakkablashadi.

1-jadval

MuddatiTa'rif
Boylikjamiyatdagi alohida a'zolar ("turlar") soni
Xilma -xillikko'pincha jamoaning boylik va tenglik xususiyatlarining o'lchovi
maxsus "xilma-xillik indeksi" sifatida hisoblanadi
Disbiyozkasal bilan bog'liq mikrobiota hamjamiyatiga murojaat qilish uchun ishlatiladigan atama
bog'langan mikrobiota hamjamiyatidan farqlanishi mumkin bo'lgan holat
sog'lom nazorat holati bilan

Mikrobiotaning metabolik funktsiyalari

Mikroblar hamjamiyatining a'zoligi va dinamikasini tavsiflagandan so'ng, mezbon fiziologiyasiga ta'sir qiladigan funktsional faoliyatni tushunish juda muhimdir. Ichak mikrobiotasi ovqat hazm qilish va ovqatlanishning ajralmas qismidir va ular mezbon tomonidan hazm bo'lmaydigan substratlardan ozuqa moddalarini ishlab chiqishi mumkin. Misol uchun, ksiloglyukanlar odatda salat va piyoz kabi parhez sabzavotlarda uchraydi va ksiloglyukanlar mikrobial hazm qilish qobiliyati yaqinda ma'lum bir turda bitta lokusda aniqlangan. Bakteroidlar (*14). Ksiloglyukanlar hazm qilish qobiliyati Bacteroidetes filumi a'zolarida nisbatan kam uchraydigan xususiyat ekanligi ko'rsatildi va bu qobiliyatning inson xosti uchun ahamiyati ommaviy metagenom ma'lumotlar bazasini tahlil qilish orqali ko'rsatildi, shuni ko'rsatdiki, odamlarning 92% kamida bittasini o'z ichiga oladi. bular kam Bakteroidlar ksiloglukanlarni hazm qilishga qodir turlar. Ushbu topilmalar odamlarning ichak mikrobiotasi bilan qanday o'zaro manfaatli munosabatlarni o'rnatganligini, bu parhez va ovqatlanishga ta'sir qilganligini ko'rsatadi.

Mikroblar qisqa zanjirli yog 'kislotalarini (SCFA) hazm bo'lmaydigan oziq-ovqat tolalaridan ozod qiladi va SCFA ichak shilliq qavati uchun muhim energiya manbai bo'lib, immunitet reaktsiyalari va ichakdagi o'smalarning rivojlanishi uchun juda muhimdir. Ichakdagi ko'p miqdorda bioaktiv SCFA bo'lgan butiratning roli yo'g'on ichak saratonida murakkab rol o'ynaydi, bu konsentratsiya va kontekstga bog'liq bo'lib ko'rinadi, chunki yaqinda o'tkazilgan ikkita preklinik tadqiqotlarda ko'rsatilgan. Butirat o'simtani bostiruvchi gen (APC) mutatsiyasiga va nomutanosiblikni tiklash geni (MSH2) etishmovchiligi bo'lgan transgen sichqonlarda o'simta hosil bo'lishini rag'batlantirishi haqida xabar berilgan, chunki antibiotiklar bilan davolash yoki kam uglevodli dieta bilan o'simta shakllanishi kamaygan, ikkalasi ham butirat darajasini pasaytiradi va ko'payadi. antibiotik bilan davolash qilingan sichqonlarga butiratni boqish (* 15). Aksincha, butirat o'simta hosil bo'lishini inhibe qilganligi xabar qilingan, chunki butirat retseptorlari bo'lgan Grp109a etishmovchiligi bo'lgan sichqonlarda yallig'lanish stimullari yoki APC mutatsiyasiga olib keladigan o'simta hosil bo'lishi kuchaygan va Grp109a orqali signalizatsiya bu stimullar tomonidan qo'zg'atilgan o'simta hosil bo'lishini inhibe qilgan (*16). Kolit va kolorektal saratonda mikrobiota tomonidan ishlab chiqarilgan butiratning roli bo'yicha keyingi tadqiqotlar kutilmoqda. Ushbu bo'limda muhokama qilingan tadqiqotlar mikrobiotaning sog'liq va kasallikdagi rolini yaxshiroq tushunish uchun uning funktsiyasini baholash zarurligini ko'rsatadi.

Xost-mikrobning immunitet tizimidagi o'zaro ta'siri

Mikrobiota va xost immun tizimi o'rtasidagi o'zaro ta'sirlar ko'p, murakkab va ikki tomonlama. Immunitet tizimi kommensal mikrobiotaga toqat qilishni va patogenlarga to'g'ri javob berishni o'rganishi kerak va o'z navbatida mikrobiota immunitet tizimini to'g'ri ishlashga o'rgatish uchun ajralmas hisoblanadi. Bu erda biz mikrobiota immunitet gomeostazasiga qanday ta'sir qilishini ko'rsatish uchun mikroblar hamjamiyatining a'zolari yallig'lanishga qarshi tartibga soluvchi T-hujayralar (Treg) differentsiatsiyasini qanday targ'ib qilishini tavsiflovchi tadqiqotlarni ta'kidlaymiz. Bir qator tajribalar shuni ko'rsatdiki, IV, XIVa va XVIII klasterlaridan Klostridiyaning patogen bo'lmagan turlari to'plami, bir qator o'ziga xos bo'lmagan selektsiya bosqichlarini qo'llashdan so'ng ajratilgan holda, yo'g'on ichak Tregni qo'zg'atishi mumkin edi va bir mexanizm butirat ishlab chiqarishni o'z ichiga olishi mumkin. Treg rivojlanishini nazorat qiluvchi Foxp3 promouterining epigenetik nazoratiga ta'sir qiladi (17, ** 18, 19-22). Endojen mikrobiotani o'z ichiga olmaydi mikrobsiz sichqonlarda, boshqa guruh ham Treg rivojlanishiga yordam beradigan bakterial shtammlar uchun inson najas namunalarini tekshirishning yangi usulini ishlab chiqdi va ular bu funktsional imkoniyatlarni kutilganidan ko'ra ko'proq shtammlarda qayd etdilar (*23). Bu erda muhokama qilinmagan bo'lsa-da, ushbu bo'limda muhokama qilingan dastlabki tug'ma mudofaadan tortib, murakkab orttirilgan javoblargacha barcha darajadagi immunitet funktsiyalariga ta'sir qiluvchi xost-mikrob o'zaro ta'siri haqida dalillar mavjud (24). Mikrobiotaning ichak ichidagi va tashqarisidagi immun gomeostaziga qanday ta'sir qilishi mumkinligini tushuntirishga katta qiziqish bor, chunki bu jarayon yallig'lanish kasalliklarining patogenezi va davolashi va yallig'lanish bilan bog'liq kasalliklarning tobora ortib borayotgan ro'yxati uchun muhim ahamiyatga ega.

Muayyan kasalliklar va sharoitlarda mikrobiotaning roli

Yuqoridagi bo'limlarda mikrobiotaning inson fiziologiyasiga ta'sir qilishi mumkin bo'lgan ko'plab usullardan ba'zilari tasvirlangan va ko'pincha disbiyoz deb ataladigan kasallik holatlari bilan bog'liq mikrobiota o'zgarishlarini o'rganishga katta qiziqish borligi ajablanarli emas (1-jadval). Biroq, hozirgi vaqtda ko'pgina misollarda dysbioz va kasallikning patogenezi o'rtasidagi munosabatlar noaniq. Kasallik bilan bog'liq qanday mikrobiota o'zgarishlari ma'noli ekanligi ko'pincha aniq emas va sabab va ta'sirni ajratish tabiatan qiyin. Mikrobiotaning uy egasiga qanday ta'sir qilishi haqida ko'proq bilib olganimizdan so'ng, disbioz kasallikka olib kelishi mumkinligi haqida taxmin qilish qiziq bo'lsa-da, kasallik holati turli mexanizmlar, jumladan, ovqatlanish odatlari va ichakdagi o'zgarishlar orqali mikrobiotaning o'zgarishiga olib kelishi mumkinligi ham qayd etilgan. funktsiyasi, shuningdek, antibiotiklar kabi dori-darmonlarni qo'shish orqali. Ushbu bo'limda biz mikrobiotaning ma'lum kasalliklar yoki sharoitlarda roli haqidagi bir nechta so'nggi topilmalarni ta'kidlaymiz, ammo biz ichak ichidagi va tashqarisidagi ko'plab boshqa kasalliklarda paydo bo'lgan barcha topilmalarga to'xtala olmaymiz, shu jumladan, lekin emas. romatoid artrit (25), kolorektal saraton (26), semizlik (27) va diabet (28) bilan cheklangan.

Yurak-qon tomir kasalligi

Mikrobiota va yurak-qon tomir kasalliklari o'rtasidagi bog'liqlikka qiziqish ortib bormoqda, chunki parhez fosfatidilxolinning trimetilamin-proaterosklerotik metabolitiga mikrobial metabolizmini ko'rsatadi.N.-oksid (TMAO) (29). Fosfatidilxolin bilan oziqlangan sog'lom bemorlarning yaqinda o'tkazilgan tadqiqoti antibiotiklar bilan oldingi davolanish natijasida bostirilgan plazma TMAO darajasining oshishini ko'rsatdi. Shuningdek, ular plazma TMAO darajasi yurak-qon tomir kasalliklari xavfi omillari bo'lgan bemorlarda yurak-qon tomir hodisalari xavfi ortishi bilan bog'liqligini aniqladilar (*30). Boshqa bir tadqiqotda, xuddi shu guruh vegetarianlar dietasiga rioya qilgan sog'lom ko'ngillilar, fosfatidilxolin bilan oziqlangandan so'ng, plazma TMAO darajasini oshirmaganligini va bu xususiyat fekal mikrobiotaning o'ziga xos tarkibi bilan bog'liqligini ko'rsatdi. *31). Shunday qilib, yurak-qon tomir kasalliklari uchun diagnostika va terapevtik salohiyatni taklif qilishi mumkin bo'lgan ushbu mikrobiotaga bog'liq yo'lga katta qiziqish bor.

Irritabiy ichak kasalligi va mikrobiota-ichak-miya o'qi

Irritabiy ichak sindromida (IBS) mikrobiotaning roli shubhali, ammo isbotlanmagan va mikrobiotani o'zgartiruvchi terapiya, jumladan, parhezni o'zgartirish, probiyotiklar va antibiotiklar, bir-biriga zid bo'lsa-da, dalda beruvchi natijalarni ko'rsatdi (32). Kichik miqdordagi avstraliyaliklarda odatiy avstraliyalik parhez bilan solishtirganda, ma'lum fermentativ substratlarni cheklangan iste'mol qilishdan iborat past FODMAP (fermentable o ligosakkaridlar, d izaxaridlar, m onosakkaridlar va p olyollar) bilan parhez aralashuvi natijalarini tavsiflovchi ikkita hisobotda. IBS bilan og'rigan bemorlarda past FODMAP dietasi simptomlarni yaxshilaydi va ichak mikrobiotasidagi o'zgarishlarga olib keldi, shu jumladan butirat ishlab chiqaradigan bakteriyalar kabi taxminiy sog'lom bakteriyalarning kamayishi. Clostridium XIVa klasteri (33, *34). IBS bilan bog'liq tavsiya etilgan yo'llardan biri mikrobiota-ichak-miya o'qi orqali ichakdagi o'zgarishlarni markaziy asab tizimidagi simptomlarni idrok etish bilan bog'laydi. Yaqinda o'tkazilgan qiziqarli hisobot probiyotiklarga boy fermentlangan sut mahsulotini iste'mol qilish nazorat mahsulotini qabul qilish bilan solishtirganda funktsional magnit-rezonans tomografiya bilan o'lchanadigan vizual hissiy stimullarga javoban miya faoliyatida o'zgarishlarga olib kelishini ko'rsatdi (35). IBSni o'rganish maxsus diagnostik testlarning yo'qligi va heterojen etiologiyalar ehtimoli tufayli qiyin. Mikrobiota o'zgarishi ayniqsa muhim bo'lgan va mikrobiota tarkibi va funktsiyasiga ta'sir qiladigan terapiya foydali bo'lgan bemorlarning bir qismi bo'lishi mumkin.

Clostridium difficile infektsiya

Clostridium difficile INFEKTSION (CDI) ichak mikrobiotasidagi jiddiy o'zgarishlar natijasida rivojlanadigan va mikrobiota asosidagi terapiya bilan samarali davolanadigan inson kasalligining yorqin namunasidir (36). Najas mikrobiota transplantatsiyasini (FMT) takroriy CDI ning oldini olish uchun qo'llanilishini ko'rib chiqish bo'yicha meta-tahlil 2012 yilgacha 273 bemor bilan 11 ta tadqiqotni aniqladi, natijada umumiy samaradorlik taxminan 90% ni tashkil etdi va FMT bilan bog'liq jiddiy nojo'ya hodisalar haqida xabar berilmagan (37). Istiqbolli klinik tadkikotda takroriy CDI bilan og'rigan bemorlar tasodifiy uchta davolash guruhidan biriga tayinlangan: standart vankomitsin terapiyasi, vankomitsin terapiyasi, keyin ichakni yuvish va vankomitsin terapiyasi, so'ngra ichakni yuvish va keyinchalik donor axlatini o'n ikki barmoqli ichakka quyish (** 38). Tadqiqot FMT ning ustunligi sababli oraliq tahlildan so'ng erta to'xtatildi. Takroriy CDI uchun FMT bilan davolangan bemorlarning najas mikrobiotasini tahlil qilish shuni ko'rsatdiki, qabul qiluvchilarning transplantatsiyadan keyingi mikrobiotasi donornikiga ko'proq o'xshash bo'ladi. 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. difficile were accompanied by changes in the metabolome that supported C. difficile germination and growth (*41). In the antibiotic-treated mice, primary bile acids that support C. difficile germination and certain carbohydrates that support C. difficile growth were present at significantly increased levels compared to control C. difficile-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.

Yallig'lanishli ichak kasalligi

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.

Trend yangiliklar

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

Kredit: Pixabay/CC0 jamoat mulki

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 Milliy fanlar akademiyasi materiallari (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 Hujayra.

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.


Transkripsiya

Bakteriyalar. Viruslar. Zamburug'lar. 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 Yangi olim. 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.