Кишечная микробиота и ее метаболиты при IGA нефропатии. Обзор литературы

IgA нефропатия (IgAН) является наиболее распространенным вариантом первичных гломерулонефритов, который диагностируют на основании выявления доминантных депозитов иммуноглобулина A в мезангильном матриксе почечных клубочков. Ключевую роль в патогенезе заболевания играет гиперпродукция галактозодефицитного IgA1, ассоциированная с лимфоидной тканью слизистых оболочек желудочно-кишечного тракта (ЖКТ). Приобретая характер аутоантигена, аберрантный IgA1 стимулирует выработку аутоантител с формированием иммунных комплексов, которые в результате взаимодействия с мезангиальными клетками почечного клубочка вызывают каскад воспалительных и пролиферативных реакций с повреждением подоцитов и эпителия проксимальных канальцев. Состояние микробиоты ЖКТ и особенно кишечника, как основного источника синтеза IgA1, является важным фактором формирования иммунного ответа на антигенную стимуляцию разной природы. Гиперреактивность слизистых, согласно данным многочисленных исследований, играет определяющую роль не только в развитии, но и прогрессировании IgAН. Широкое внедрение технологий мета-геномного ДНК-секвенирования позволило выявить у пациентов с IgAН снижение микробного разнообразия кишечной флоры по сравнению со здоровой популяцией. Не менее важным результатом исследований явилось определение в геноме больных IgAН локусов, ассоциированных с нарушением проницаемости слизистой кишечника и риском развития его воспалительных заболеваний, которые, как выяснилось при анализе причинно-следственных связей, повышали вероятность возникновения IgAН. Кроме того, обнаружена связь между генетической предрасположенностью к IgAН, обусловленной, как полагают, мультилокусным взаимодействием аллелей риска, и состоянием микробиоты. В частности, при IgAН отмечено возрастание числа бактерий семейств Sutterellaceae и Enterobacteriaceae, способных в результате избыточной продукции липополисахаридов подавлять экспрессию гена мРНК специфического молекулярного шаперона (Cosmc) – важного компонента процесса гликозилирования IgA1. У пациентов с IgAН также выявлена прямая корреляция между количеством отдельных бактерий семейств Actinobacteriaceae, Ruminococcaceae и Bacteroidaceae и такими клинико-лабораторными показателями, как протеинурия, микрогематурия и скорость клубочковой фильтрации. В условиях дисбиоза кишечника наблюдается нарушение продукции бактериальных метаболитов, среди которых особое место занимают короткоцепочечные жирные кислоты (КЖК). Благодаря своим физиологическим эффектам, КЖК способны регулировать проницаемость слизистой оболочки кишечника, модулировать интенсивность иммунного ответа и антиоксидантную активность, влияя таким образом на характер течения IgAН.

Анализ состояния микробиоценоза кишечника с количественной оценкой отдельных видов бактерий, а также уровня их метаболитов, представляется актуальным направлением дальнейших исследований, которые позволят разработать новые подходы к персонифицированной терапии пациентов с IgAН.

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