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Экспериментальная и клиническая гастроэнтерология

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НАРУШЕНИЯ МИКРОБНОГО И ЭНДОГЕННОГО МЕТАБОЛИЗМА ПРИ ЯЗВЕННОМ КОЛИТЕ И ЦЕЛИАКИИ: МЕТАБОЛОМНЫЙ ПОДХОД К ВЫЯВЛЕНИЮ ПОТЕНЦИАЛЬНЫХ БИОМАРКЕРОВ ХРОНИЧЕСКОГО ВОСПАЛЕНИЯ В КИШЕЧНИКЕ, СВЯЗАННОГО С ДИСБИОЗОМ

Аннотация

Цель исследования: выявление потенциальных биомаркеров язвенного колита и целиакии путем изучения метаболома сыворотки крови. Материалы и методы: В исследование было включено 125 пациентов: 40 пациентов с язвенным колитом, 43 пациента с целиакией и 42 практически здоровых добровольца. Состав метаболома сыворотки крови определялся с помощью метода газовой хроматографии - масс-спектрометрии (ГХ-МС). Результаты: Из 93 идентифицированных соединений, общих для всех пациентов, 28 метаболитов имели микробное происхождение. У пациентов с язвенным колитом концентрации молочной, 2-гидроксимасляной, 3-гидроксиизомасляной, 2-гидроксиизовалериановой, 3-гидроксикоричной, янтарной, бензойной и парагидроксифенилуксусной кислот в сыворотке крови были значимо повышены по сравнению со здоровыми. В свою очередь, уровни капроновой, линолевой и эйкозадиеновой кислот при язвенном колите были значимо ниже, чем в группе здоровых. Концентрации 2-гидроксимасляной и 2-гидроксиизовалериановой кислот у больных язвенным колитом были значимо повышены и по сравнению с пациентами с целиакией. Концентрации капроновой, линолевой и гликолевой кислот при язвенном колите были значимо ниже, чем в группе целиакии. У пациентов с целиакией концентрации стеариновой, 2-гидроксиизовалериановой, янтарной, фумаровой и бензойной кислот были значимо повышены по сравнению со здоровыми добровольцами, а уровень арахидоновой кислоты был значимо повышен только по сравнению с больными язвенным колитом. Липогенный индекс (C16:0/C 18:2n-6) был значимо повышен у пациентов с язвенным колитом по сравнению как со здоровыми добровольцами, так и с больными целиакией. Индекс активности элонгазы ELOVL6 (C18:0/C16:0) и отношение уровня стеариновой кислоты к уровню линолевой кислоты (C18:0/C18:2n-6) у пациентов с язвенным колитом были значимо повышены по сравнению со здоровыми. Отношение уровня арахидоновой кислоты к уровню эйкозадиеновой кислоты (C20:4n-6/C20:2n-6) было повышено в обеих группах больных. На фоне дополнительного применения масляной кислоты в комбинации с инулином отмечалось значимое понижение сывороточных концентраций провоспалительных метаболитов микробного происхождения - янтарной кислоты (как у больных язвенным колитом, так и у пациентов с целиакией) и 2-гидроксиизовалериановой кислоты (у больных целиакией). Кроме того, у пациентов с язвенным колитом значимо повышался уровень линолевой и эйкозадиеновой кислот. Выводы: Как при язвенном колите, так и при целиакии наблюдаются значимые изменения сывороточных концентраций метаболитов микробного и эндогенного происхождения, отражающие нарушения в соответствующих метаболических путях (гликолиз, цикл Кребса, окисление и биосинтез жирных кислот, метаболизм кетоновых тел, метаболизм триптофана, фенилаланина и тирозина, микробный метаболизм). По результатам ROC-анализа, некоторые из этих метаболитов (преимущественно микробного или смешанного происхождения), а также новый метаболомный индекс (отношение уровня арахидоновой кислоты к уровню эйкозадиеновой кислоты), отражающий баланс между провоспалительными и противовоспалительными компонентами пула ω-6-ПНЖК, могут рассматриваться как потенциальные биомаркеры хронического воспаления в кишечнике. Снижение уровня провоспалительных метаболитов микробного происхождения в сыворотке крови свидетельствует о возможности эффективной коррекции метаболического дисбиоза с помощью метабиотиков при обоих заболеваниях.

Об авторах

С. И. Ситкин
Гос. НИИ ОЧБ ФМБА России; СЗГМУ им. И. И. Мечникова Минздрава России
Россия


Т. Я. Вахитов
Гос. НИИ ОЧБ ФМБА России
Россия


Е. И. Ткаченко
Военно-медицинская академия имени С. М. Кирова
Россия


Л. Б. Лазебник
МГМСУ им. А. И. Евдокимова Минздрава России
Россия


Л. С. Орешко
СЗГМУ им. И. И. Мечникова Минздрава России
Россия


Т. Н. Жигалова
СЗГМУ им. И. И. Мечникова Минздрава России
Россия


В. Г. Радченко
СЗГМУ им. И. И. Мечникова Минздрава России
Россия


Е. Б. Авалуева
СЗГМУ им. И. И. Мечникова Минздрава России
Россия


П. В. Селиверстов
СЗГМУ им. И. И. Мечникова Минздрава России
Россия


В. А. Утсаль
Институт токсикологии ФМБА России
Россия


Э. В. Комличенко
НМИЦ им. В. А. Алмазова Минздрава России
Россия


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Ситкин С.И., Вахитов Т.Я., Ткаченко Е.И., Лазебник Л.Б., Орешко Л.С., Жигалова Т.Н., Радченко В.Г., Авалуева Е.Б., Селиверстов П.В., Утсаль В.А., Комличенко Э.В. НАРУШЕНИЯ МИКРОБНОГО И ЭНДОГЕННОГО МЕТАБОЛИЗМА ПРИ ЯЗВЕННОМ КОЛИТЕ И ЦЕЛИАКИИ: МЕТАБОЛОМНЫЙ ПОДХОД К ВЫЯВЛЕНИЮ ПОТЕНЦИАЛЬНЫХ БИОМАРКЕРОВ ХРОНИЧЕСКОГО ВОСПАЛЕНИЯ В КИШЕЧНИКЕ, СВЯЗАННОГО С ДИСБИОЗОМ. Экспериментальная и клиническая гастроэнтерология. 2017;(7):4-50.

For citation:


Sitkin S.I., Vakhitov T.Ya., Tkachenko E.I., Lazebnik L.B., Oreshko L.S., Zhigalova T.N., Radchenko V.G., Avalueva E.B., Seliverstov P.V., Utsal V.A., Komlichenko E.V. GUT MICROBIAL AND ENDOGENOUS METABOLISM ALTERATIONS IN ULCERATIVE COLITIS AND CELIAC DISEASE: A METABOLOMICS APPROACH TO IDENTIFY CANDIDATE BIOMARKERS OF CHRONIC INTESTINAL INFLAMMATION ASSOCIATED WITH DYSBIOSIS. Experimental and Clinical Gastroenterology. 2017;(7):4-50. (In Russ.)

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