sibmedСибирский научный медицинский журналСибирский научный медицинский журнал2410-25122410-2520ИЦиГ СО РАН10.18699/SSMJ20250301sibmed-2223Research ArticleОБЗОРЫREVIEWSГиперлипидемия и микробиота кишечника: роль пребиотиков, пробиотиков, статинов и фибратовHyperlipidemia and gut microbiota: the role of prebiotics, probiotics, statins and fibrateshttps://orcid.org/0000-0003-0069-7744ГригорьеваИ. Н.Grigor’evaI. N.

Ирина Николаевна Григорьева, д. м. н., проф.

630089; ул. Бориса Богаткова, 175/1; Новосибирск

Irina N. Grigor’eva, doctor of medical sciences, professor

630089; Boris Bogatkov st., 175/1; Novosibirsk

grigorieva2024@yandex.ruhttps://orcid.org/0000-0002-9734-1826ТовН. Л.TovN. L.

Никита Львович Тов, д. м. н., проф.

630090; Красный пр., 52; Новосибирск

Nikita L. Tov, doctor of medical sciences, professor

630090; Krasny ave., 52; Novosibirsk

nikita.tov@gmail.comНепомнящихД. Л.NepomnyashchikhD. L.

Давид Львович Непомнящих, д. м. н., проф.

630090; Красный пр., 52; Новосибирск

David L. Nepomnyashchikh, doctor of medical sciences, professor

630090; Krasny ave., 52; Novosibirsk

dln_nco@mail.ruНИИ терапии и профилактической медицины – филиал ФИЦ Институт цитологии и генетики СО РАНРоссияResearch Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesRussian FederationНовосибирский государственный медицинский университет Минздрава РоссииРоссияNovosibirsk State Medical University of Minzdrav of RussiaRussian Federation202513072025453616Copyright © Григорьева И.Н., Тов Н.Л., Непомнящих Д.Л., 20252025Григорьева И.Н., Тов Н.Л., Непомнящих Д.Л.Grigor’eva I.N., Tov N.L., Nepomnyashchikh D.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://sibmed.elpub.ru/jour/article/view/2223

   Цель исследования ‒ охарактеризовать микробиоту кишечника и ее метаболиты при гиперлипидемии и проанализировать ассоциации между микробиотой кишечника и некоторыми биологическими (пребиотики и пробиотики) и гиполипидемическими (статины, фибраты) препаратами при лечении гиперлипидемий.

   При гиперлипидемии повышено количество бактерий, продуцирующих токсические метаболиты, такие как липополисахарид и триметиламин-N-оксид (Bacillota (бывшие Firmicutes), Pseudomonadota (бывшие Proteobacteria), Desulfovibrionaceae), и снижено число кишечных продуцентов полезных короткоцепочечных жирных кислот и содержание гидролазы желчных солей (Bacteroidota (бывшие Bacteroidetes), Verrucomicrobia, Bifidobacterium, Lactobacillus, Streptococcus, Eubacterium). Пребиотики могут улучшать липидный обмен, однако механизмы такого эффекта остаются неизвестными. Пробиотики (наиболее хорошо изучены Lactobacillus и Bifidobacterium) способны удалять холестерин из циркуляции (адсорбируя и ассимилируя его на клеточных мембранах), уменьшать его всасывание (стимулируя синтез желчных кислот de novo) и модулировать синтез (ингибируя ГМГ-КоА-редуктазу и снижая экспрессию генов семейства транспортеров АТФ-связывающей кассеты типа A1). Lactobacillus, помимо улучшения кишечного микробного профиля и липидного обмена, снижает массу тела, АД, воспаление и инсулинорезистентность. Статины и кишечная микробиота демонстрируют обоюдное влияние: лучший ответ на лечение статинами связан с более высоким разнообразием микробиоты, а статины способны восстанавливать измененную при патологии микробиоту (уменьшать количество потенциальных патогенов, таких как Parabacteroides merdae, и увеличивать количество полезных бактерий – Bifidobacterium longum, Bifidobacterium bifidum, Anaerostipes hadrus, Faecalibacterium prausnitzii, Akkermansia muciniphila, род Oscillospira, а также снижать уровень триметиламин-N-оксида в плазме). При этом влияние статинов на состав и функцию микробиоты кишечника не зависит от снижения уровня холестерина. Данные об эффектах фибратов на микробиоту, изученных на мышах, противоречивы: в одних работах фенофибрат может ослаблять системное воспаление и нарушения липидного обмена, вызванные высокожировой диетой, в других – наоборот, стимулирует ожирение и воспаление.

   Заключение. Микробиом кишечника открывает принципиально новые подходы к лечению кардиометаболических заболеваний в эпоху прецизионной медицины.

   Aim of the study was to characterize the intestinal microbiota and its metabolites in hyperlipidemia and analyze the associations between the intestinal microbiota and some biological (prebiotics and probiotics) and lipid-lowering (statins, fibrates) drugs in the treatment of hyperlipidemia.

   In hyperlipidemia, the number of bacteria producing toxic metabolites such as lipopolysaccharide and trimethylamine-N-oxide (TMAO) is increased (Bacillota (former Firmicutes), Pseudomonadota (former Proteobacteria), Desulfovibrionaceae) and the number of intestinal producers of beneficial short-chain fatty acids and bile salt hydrolase is decreased (Bacteroidota (former Bacteroidetes), Verrucomicrobia, Bifidobacterium, Lactobacillus, Streptococcus, Eubacterium). Prebiotics can improve lipid metabolism, but the mechanisms of such effect remain unknown. Probiotics (the best studied are Lactobacillus and Bifidobacterium) can remove cholesterol from circulation (by adsorbing and assimilating it on cell membranes), reduce intestinal absorption of cholesterol (by stimulating de novo bile acid synthesis), and modulate cholesterol synthesis (by inhibiting HMG-CoA reductase and reducing the expression of the ATP-associated cassette transporter type A1 gene family). Lactobacillus, in addition to improving the intestinal microbial profile and lipid metabolism, reduces body weight, blood pressure, inflammation, and insulin resistance. Statins and the intestinal microbiota demonstrate mutual influence: a better response to statin treatment is associated with a higher diversity of microbiota, statins are also able to restore the microbiota altered due to pathology to a healthier state (reduce the number of potential pathogens, such as Parabacteroides merdae, and increase the number of beneficial bacteria – Bifidobacterium longum, Bifidobacterium bifidum, Anaerostipes hadrus, Faecalibacterium prausnitzii, Akkermansia muciniphila and the genus Oscillospira, and reduce plasma TMAO levels). Moreover, the effect of statins on the composition and function of the gut microbiota does not depend on a decrease in cholesterol level. The data on the effects of fibrates on the microbiota, studied in mice, are contradictory: in some studies, fenofibrate can reduce caused by a high-fat diet systemic inflammation and lipid metabolism disorders, while in others, on the contrary, it can increase obesity and inflammation.

   Conclusions. The gut microbiome opens up fundamentally new approaches to the treatment of cardiometabolic diseases in the era of precision medicine.

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The authors declare that there are no conflicts of interest present.