diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM12893diaendo-12893Research ArticleКлинический случайCase reportТрансплантация фекальной микробиоты в составе комплексной терапии сахарного диабета у сибсов с ожирением: клинический случайFeсal microbiota transplantation in the format of complex therapy in obesive siblings: clinical casehttps://orcid.org/0000-0001-5268-430XПокровскаяЕ. В.PokrovskayaE. V.

Покровская Елена Владиславовна, научный сотрудник

117036, Москва, ул. Дмитрия Ульянова, д. 11

eLibrary SPIN: 8769-5010

Elena V. Pokrovskaya, MD, research associate

11, Dm. Ulyanova street, 117036 Moscow

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pokrovskaya.93@mail.ruЖгунЕ. С.ZhgunE. S.

Жгун Елена Сергеевна, кандидат биологичнских наук, старший научный сотрудник

Москва

eLibrary SPIN: 7696-5117

Elena S. Zhgun, PhD in Biology, senior research associate

Moscow

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al.androva@gmail.comhttps://orcid.org/0000-0001-6612-6851ШестаковаЕ. А.ShestakovaE. A.

Шестакова Екатерина Алексеевна, кандидат медицинских наук, ведущий научный сотрудник

Москва

eLibrary SPIN: 1124-7600

Ekaterina A. Shestakova, MD, PhD, leading research associate

Moscow

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katiashestakova@mail.ruhttps://orcid.org/0000-0002-7768-4717СкляникИ. А.SklyanikI. A.

Скляник Игорь Александрович, кандидат медицинских наук, старший научный сотрудник

Москва

eLibrary SPIN: 7081-8077

Igor A. Sklyanik, MD, PhD, senior research associate

Moscow

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sklyanik.igor@gmail.comhttps://orcid.org/0000-0001-7489-7250ФедюшкинаИ. В.FedushkinaI. V.

Федюшкина Ирина Викторовна, кандидат биологичнских наук, научный сотрудник

Москва

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Irina V. Fedyushkina, PhD in Biology, research associate

Moscow

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ivf@rcpcm.orghttps://orcid.org/0000-0003-4899-342XОлехновичЕ. И.OlekhnovichE. I.

Олехнович Евгений Иванович, кандидат биологичнских наук, научный сотрудник

Москва

Evgeniy I. Olekhnovich, PhD in Biology, research associate

Moscow

jeniaole13@mail.ruhttps://orcid.org/0000-0002-1217-9234КонановД. Н.KonanovD. N.

Конанов Дмитрий Николаевич, младший научный сотрудник

Москва

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Dmitry N. Konanov, junior research associate

Moscow

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konanovdmitriy@gmail.comhttps://orcid.org/0000-0001-7231-3629КардонскийД. А.KardonskyD. A.

Кардонский Дмитрий Александрович

 Москва

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Dmitry A. Kardonsky

Moscow

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freddy1178@yandex.ruКислунЮ. В.KislunYu. V.

 Кислун Юрий Викторович, кандидат биологических наук

Москва

Yuriy V. Kislun, PhD in Biology

Moscow

u.kislun@list.ruСорокинаЕ. А.SorokinaE. A.

Сорокина Екатерина Андреевна, студентка

Москва

 

Ekaterina Sorokina, student

Moscow

sorokina1901@mail.ruhttps://orcid.org/0000-0002-0316-8314ЗильберманЛ. И.ZilbermanL. I.

Зильберман Любовь Иосифовна, кандидат медицинских наук, ведущий научный сотрудник

 Москва

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Lubov I. Zilberman, MD, PhD, leading research associate

Moscow

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zilbermanl@yandex.ruhttps://orcid.org/0000-0001-9235-5594ЗайцеваН. В.ZaytsevaN. V.

Зайцева Наталья Владиславовна, кандидат медицинских наук, ведущий научный сотрудник

Москва

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Natalia V. Zaytseva, MD, PhD, leading research associate

Moscow

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nata.zaec@gmail.comhttps://orcid.org/0000-0003-0130-5079ИльинаЕ. Н.IlinaE. N.

Ильина Елена Николаевна, член-корреспонден РАН, доктор биологических наук, профессор РАН

Москва

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Elena N. Ilina, PhD in Biology, Professor

Moscow

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ilinaen@gmail.comhttps://orcid.org/0000-0003-0837-8764ГоворунВ. М.GovorunV. M.

Говорун Вадим Маркович, доктолр биологических наук, академик РАН

Москва

eLibrary SPIN: 4187-7742

Vadim M. Govorun, PhD in Biology

Moscow

eLibrary SPIN: 4187-7742

vgovorun@yandex.ruhttps://orcid.org/0000-0002-5057-127XШестаковаМ. В.ShestakovaM. V.

Шестакова Марина Владимировна, доктор медицинских наук, профессор, академик РАН

Москва

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Marina V. Shestakova, MD, PhD, Professor

Moscow

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nephro@endocrincentr.ruНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian FederationФедеральный научно-клинический центр физико-химической медициныРоссияFederal Research and Clinical Center of Physical-Chemical MedicineRussian Federation202229082022254405417Copyright © Покровская Е.В., Жгун Е.С., Шестакова Е.А., Скляник И.А., Федюшкина И.В., Олехнович Е.И., Конанов Д.Н., Кардонский Д.А., Кислун Ю.В., Сорокина Е.А., Зильберман Л.И., Зайцева Н.В., Ильина Е.Н., Говорун В.М., Шестакова М.В., 20222022Покровская Е.В., Жгун Е.С., Шестакова Е.А., Скляник И.А., Федюшкина И.В., Олехнович Е.И., Конанов Д.Н., Кардонский Д.А., Кислун Ю.В., Сорокина Е.А., Зильберман Л.И., Зайцева Н.В., Ильина Е.Н., Говорун В.М., Шестакова М.В.Pokrovskaya E.V., Zhgun E.S., Shestakova E.A., Sklyanik I.A., Fedushkina I.V., Olekhnovich E.I., Konanov D.N., Kardonsky D.A., Kislun Y.V., Sorokina E.A., Zilberman L.I., Zaytseva N.V., Ilina E.N., Govorun V.M., Shestakova M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/12893

Ожирение и связанные с ним метаболические заболевания часто сопровождаются изменениями кишечной микробиоты, приводящими к снижению разнообразия генов метагенома. Одним из наиболее эффективных методов коррекции микрофлоры кишечника является трансплантация фекальной микробиоты (ТФМ), полученной от здоровых доноров, хорошо зарекомендовавшая себя при лечении инфекций, вызываемых Clostridium difficile. Применение ТФМ для коррекции метаболических расстройств перспективно, однако данные о ее использовании ограничены и имеют противоречивые результаты. В нашей работе двум пациентам (родным братьям) с ожирением II степени и различными типами сахарного диабета (СД) (старший брат (44 года) с СД 2 типа (СД2), младший брат (39 лет) с СД 1 типа (СД1)) была проведена ТФМ в составе комплексной противодиабетической терапии. У обоих пациентов в ходе лечения отмечено снижение массы тела (динамика — 4–5 кг за первый месяц наблюдения, далее — 1–2 кг в месяц). Через 1 год после ТФМ у пациента с СД2 отмечены снижение выраженности инсулинорезистентности (ИР), оцененной методом гиперинсулинемического эугликемического клэмп-теста (исходный М-индекс 2,42 мг/кг/мин, через 1 год — 3,83 мг/кг/мин), а также сохранение удовлетворительной компенсации углеводного обмена при уменьшении объема проводимой сахароснижающей терапии. У пациента с СД1 значимой динамики показателей углеводного обмена, включая уровень гликированного гемоглобина, дозы инсулина и показатель индекса ИР, не выявлено. Метагеномное секвенирование образцов кала (n=20), собранных от обоих пациентов до и в течение 1 года после проведения ТФМ, показало отсутствие значимых изменений в таксономическом профиле микробиоты на уровне микробных семейств. Метаболомный анализ состава фекалий показал отсутствие направленных изменений в композиции метаболитов после процедуры ТФМ, характер изменений внутри группы образцов от каждого пациента в течение всего периода исследования носит случайный характер. Таким образом, ТФМ не оказала влияния на течение СД1, но послужила пусковым моментом для снижения массы тела и улучшения показателей гликемии при СД2. Однако убедительных данных, подтверждающих причинно-следственную взаимосвязь между ТФМ и улучшением течения СД2, не получено.

Obesity and associated metabolic diseases are often accompanied by changes in the gut microbiota leading to metagenome gene diversity decrease. Fecal microbiota transplantation (FMT) is one of the most effective methods for correcting the  intestinal microflora. FMT obtained from healthy donors has been proven to be an effective treatment of infections caused by Clostridium difficile. The use of FMT for correction of metabolic disorders is promising, however, data on its application is limited and has contradictory results. In our work, two patients (siblings) presented with obesity grade II and various types of diabetes mellitus (DM): the older brother (44 years old) with diabetes mellitus type 2 (DM 2), a younger brother (39 years old) with diabetes mellitus type 1 (DM 1). Both patients underwent FMT as part of complex antidiabetic therapy. During the course of treatment, a decrease in body weight was noted in both patients (4–5 kg for the first month of observation, then -1–2 kg per month). One year after FMT, a patient with type 2 diabetes showed a decrease in the severity of insulin resistance (IR), measured by the hyperinsulinemic euglycemic clamp test (initial M-index 2.42 mg/kg*min, after 1 year — 3.83 mg/kg* min) as well as the maintenance of satisfactory carbohydrate metabolism compensation against the diminishing the hypoglycemic therapy. In a patient with DM 1, no significant dynamics of carbohydrate exchange indices, including detected glycated hemoglobin (HbA1c), insulin dose and IR were during the observation period. Metagenomic sequencing of stool samples (n = 20) collected from both patients before and within 1 year after FMT showed no significant changes in the taxonomic profile of the microbiota at the level of microbial families. Metabolomic analysis of the composition of feces showed no directed changes in the composition of metabolites after the FMT procedure, the nature of changes within the samples from each patient during the entire study period was random. Thus, FMT had no effect on the course of DM1, but served as a starting point for weight loss and improvement glucose profile in DM2. However, convincing data confirming a causal correlation between FMT and improvement in the course of T2DM have not been obtained.

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