vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2024-21-4-334-344vestim-1002Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEОсобенности возрастных изменений кишечной микробиоты крыс линии Wistar при действии антибиотиков и пребиотика 2′-фукозиллактозыAge-related features of the intestinal microbiota changes in Wistar rat pups after application of antibiotics and prebiotic 2′-fucosyllactoseЖабинскаяА. А.ZhabinskayaA. A.

Жабинская Алеся Александровна – мл. науч. сотрудник

ул. Академическая, 28, 220072, г. Минск

Alesia A. Zhabinskaya ‒ Researcher

28, Akademicheskaya Str., 220072, Minsk

lesiaalex26@gmail.comМелик-КасумовТ. Б.Melik-KasumovT. B.

Мелик-Касумов Тигран Беглярович – канд. биол. наук, заведующий лабораторией

ул. Академическая, 28, 220072, г. Минск

Tigran B. Melik-Kasumov ‒ Ph. D. (Biol.), Head of the Laboratory

28, Akademicheskaya Str., 220072, Minsk

tigranbmk@gmail.comПыжА. Э.PyzhH. E.

Пыж Анна Эдуардовна ‒ канд. биол. наук, ст. науч. сотрудник

ул. Академическая, 28, 220072, г. Минск

Hanna E. Pyzh ‒ Ph. D. (Biol.)., Senior Researcher

28, Akademicheskaya Str., 220072, Minsk

Hanna.pyzh@gmail.comИнститут физиологии НАН БеларусиInstitute of Physiology of the National Academy of Sciences of Belarus202430112024214334­-344Copyright © Жабинская А.А., Мелик-Касумов Т.Б., Пыж А.Э., 20242024Жабинская А.А., Мелик-Касумов Т.Б., Пыж А.Э.Zhabinskaya A.A., Melik-Kasumov T.B., Pyzh H.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/1002

Результаты многочисленных исследований, проведенных в последние десятилетия, показали, что кишечная микробиота может существенно влиять на организм хозяина. Активное развитие кишечной микробиоты в первые годы жизни происходит параллельно с развитием нервной, эндокринной и иммунной систем. Учитывая это, кишечный дисбиоз в раннем возрасте может привести к нарушению формирования регуляторных систем макроорганизма. В этих условиях пребиотики молока могут оказывать позитивный корректирующий эффект.

Цель настоящего исследования – изучить особенности развития антибиотик-ассоциированного дисбиоза в раннем постнатальном периоде у крыс и оценить влияние 2′-фукозиллактозы в норме и на фоне развития дисбиоза.

Исследование проводили на крысах линии Wistar в возрасте 12‒26 сут. Для развития дисбиоза в раннем возрасте были использованы: смесь ампициллина тригидрата 75 мг/кг и метронидазола 50 мг/кг и смесь амоксициллина  30 мг/кг и цефалексина 20 мг/кг в течение 3 сут, начиная с 12-х суток жизни. В качестве пребиотика использовали 2′-фукозиллактозу в дозе 1 г/кг, начиная с 12-х суток до последнего дня эксперимента.

У контрольных крысят обнаружены возрастные изменения содержания бифидобактерий и энтерококков: к возрасту 26 сут отмечалось снижение их титра в кишечнике. Смесь ампициллина тригидрата 75 мг/кг и метронидазола 50 мг/кг оказывает сильный дисбиотический эффект, выражающийся в уменьшении титра бифидобактерий, лактобацилл и энтерококков кишечника. Однако через 5 сут после прекращения введения антибиотиков в период продолжающегося вскармливания молоком отмечается восстановление всех перечисленных показателей. Применение 2′-фукозиллактозы способствует сохранению титра Bifidobacterium spp. и Enterococcus spp., при этом данный пребиотический эффект сохраняется на фоне ранее перенесенного дисбиоза.

Полученные результаты указывают на то, что применение антибиотиков в раннем возрасте вызывает временные, но мощные дисбиотические изменения в толстом кишечнике. Вместе с тем применение 2′-фукозиллактозы приводит к сохранению важных пробиотических групп бактерий кишечника как в норме, так и после перенесенного дисбиоза.

The gut microbiota plays an important role in the formation of the body’s regulatory systems (nervous, endocrine, immune), which is especially important at an early age. Hence, gut dysbiosis can lead to an impaired development of both the intestinal microbiota and these regulatory systems. Prebiotics can have a positive effect on the development of the intestinal microbiome, which can correct negative changes.

The aim of this study is to investigate the features of development of antibiotic-associated dysbiosis in the early postnatal period in rats and to evaluate the effect of 2′-fucosyllactose in health and during dysbiosis.

The study was conducted on Wistar rats aged 12–26 days. To develop dysbiosis at an early age, the following mixtures were used: a mixture of ampicillin trihydrate 75 mg/kg and metronidazole 50 mg/kg and a mixture of amoxicillin 30 mg/kg and cephalexin 20 mg/kg for three days, starting on the 12th day of life. As a prebiotic 2′-fucosyllactose at a dose of 1 g/kg was used, starting on the 12th day and to the last experiment day.

In healthy animals, there is a decrease in the gut content of Bifidobacterium spp. and Enterococcus spp. at the age  of 26 days. A mixture of ampicillin trihydrate 75 mg/kg and metronidazole 50 mg/kg leads to gut dysbiosis – growth suppression of bifidobacteria, lactobacilli and enterococci. After the end of antibiotics application and continued lactation,  the titer of the described bacteria is restored. 2′-fucosyllactose has an effect on the preservation of the titer of Bifidobacterium spp. and Enterococcus spp., both in healthy animals and after early dysbiosis.

Our results indicate that antibiotic-associated dysbiosis at an early age is characterized by a temporary but powerful effect. At the same time, the use of 2′-fucosyllactose leads to preserving important probiotic groups of intestinal bacteria, both in health and after dysbiosis.

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