Перспективні напрями лікування метаболічно-асоційованої стеатотичної хвороби печінки. Фокус на мікробіоту кишечника. Огляд
DOI:
https://doi.org/10.30978/MG-2024-4-64Ключові слова:
метаболічно‑асоційована стеатотична хвороба печінки, мікробіота кишечника, пробіотики, трансплантація фекальної мікробіотиАнотація
З огляду на тісний зв’язок порушень кишкової мікробіоти з патогенетичними ланками метаболічно‑асоційованої стеатотичної хвороби печінки (МАСХП) перспективним є застосування лікувальних методик, спрямованих на модуляцію мікробіому. Найпотужніші чинники впливу на кишкову мікробіоту — характер харчування і ступінь фізичної активності, тому при лікуванні насамперед слід розглядати дієтичні втручання та рекомендації щодо фізичної активності, які є основною частиною терапії МАСХП. У цьому аспекті втручання, націлені на вісь кишечник — печінка та кишковий мікробіом, відкривають широкі можливості для розробки персоналізованих і таргетних методів лікування MAСХП. Розроблено багато молекул, що модулюють мікробіоту кишечника, більшість із них належать до пребіотиків, пробіотиків, синбіотиків. У дослідженнях показано, що застосування пробіотиків ефективне в лікуванні МАСХП за рахунок зниження ендотоксинемії, рівня печінкових амінотрансфераз, ступеня стеатозу печінки, поліпшення чутливості до інсуліну, нормалізації обміну ліпідів і позитивного впливу на мітохондрії гепатоцитів. Синбіотики, пребіотики та фітохімічні препарати з пребіотичною активністю дають у пацієнтів із МАСХП аналогічні пробіотикам ефекти — збільшення вмісту корисних бактерій у кишечнику, зниження метаболічної ендотоксемії та системного запалення, зменшення порушень обміну глюкози та ліпідів, стеатозу печінки. Дедалі більше клінічних даних указують на позитивні ефекти застосування при МАСХП пробіотиків із грибів і протигрибкових засобів: зниження жирової маси та гіперінсулінемії, зменшення запалення й фіброзу печінки. Також цікаві результати отримано при використанні топічних антибіотиків, зокрема завдяки їхньому впливу на цілісність кишкового бар’єра та еубіотичні властивості. Трансплантацію фекальної мікробіоти також розглядають як потенційний терапевтичний метод ребіозу кишечника при МАСХП. Клінічні дані щодо її застосування дуже обнадійливі: зниження рівня глюкози, інсуліну та глікованого гемоглобіну (хоча і в короткостроковій перспективі), зниження підвищеної проникності кишкового бар’єра й ступеня стеатозу печінки. Однак залишається актуальною потреба в проведенні масштабних рандомізованих досліджень для перевірки результатів застосування пребіотиків, пробіотиків, трансплантації фекальної мікробіоти, мікобіотиків для визначення оптимального режиму, тривалості й штамів мікроорганізмів, які мають найбільші переваги. Нові підходи, зокрема використання модифікованих пробіотичних бактерій і бактеріофагів, є багатообіцяючими, але їхню роль у клінічній практиці слід з’ясувати.
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