Almanac of Clinical MedicineAlmanac of Clinical MedicineАльманах клинической медицины2072-05052587-9294Moscow Regional Research and Clinical Institute (MONIKI)1731510.18786/2072-0505-2024-52-026REVIEW ARTICLEОБЗОРReview ArticleChronic constipation: focus on microbiome-targeted therapies with prebiotics, probiotics, and synbioticsХронический запор: фокус на микробиом-модулирующей терапии пребиотиками, пробиотиками и синбиотикамиhttps://orcid.org/0000-0001-9600-3131SerkovaMargarita Y.СерковаМаргарита Юрьевна
Russian Federation

MD, PhD, Assistant Professor, Chair of Propaedeutics of Internal Diseases, Gastroenterology and Dietetics named after S.M. Ryss

канд. мед. наук, ассистент кафедры пропедевтики внутренних болезней, гастроэнтерологии и диетологии им. С.М. Рысса

serkova.margarita@yandex.ruhttps://orcid.org/0000-0001-6011-0998AvaluevaElena B.АвалуеваЕлена Борисовна
Russian Federation

MD, PhD, Professor, Chair of Propaedeutics of Internal Diseases, Gastroenterology and Dietetics named after S.M. Ryss

д-р мед. наук, профессор кафедры пропедевтики внутренних болезней, гастроэнтерологии и диетологии им. С.М. Рысса

avalueva@mail.ruhttps://orcid.org/0000-0003-0331-0963SitkinStanislav I.СиткинСтанислав Игоревич
Russian Federation

MD, PhD, Associate Professor, Chair of Propaedeutics of Internal Diseases, Gastroenterology and Dietetics named after S.M. Ryss; Head of the Epigenetics & Metagenomics Research Group, Institute of Perinatology and Pediatrics; Leading Research Fellow, Laboratory of Personalized Microbial Therapy

канд. мед. наук, доцент кафедры пропедевтики внутренних болезней, гастроэнтерологии и диетологии им. С.М. Рысса; зав. научно-исследовательской группой эпигенетики и метагеномики Института перинатологии и педиатрии; вед. науч. сотр. лаборатории персонифицированной микробной терапии

drsitkin@gmail.comNorth-Western State Medical University named after I.I. MechnikovФГБОУ ВО «Северо-Западный государственный медицинский университет имени И.И. Мечникова» Минздрава РоссииAlmazov National Medical Research CentreФГБУ «Национальный медицинский исследовательский центр имени В.А. Алмазова» Минздрава РоссииInstitute of Experimental MedicineФГБНУ «Институт экспериментальной медицины»04112024161120245252802960708202430092024Copyright ©; 2024, Serkova M.Y., Avalueva E.B., Sitkin S.I.Copyright ©; 2024, Серкова М.Ю., Авалуева Е.Б., Ситкин С.И.2024Serkova M.Y., Avalueva E.B., Sitkin S.I.Серкова М.Ю., Авалуева Е.Б., Ситкин С.И.https://creativecommons.org/licenses/by-nc/4.0https://almclinmed.ru/jour/article/view/17315

Chronic constipation is a global medical, social, and economic problem due to its negative impact on patients’ quality of life and increased risk of colorectal cancer, cardiovascular and cerebrovascular disorders.

The gut microbiota plays an important role in the pathophysiology of constipation through its interplay with the immune system, enteral and central nervous system, representing a promising therapeutic target. Gut dysbiosis in patients with constipation is characterized by reduced relative numbers of bacteria producing lactate (Lactobacillaceae, Bifidobacteriaceae) and butyrate (Lachnospiraceae, Oscillospiraceae), as well as with increased numbers of those producing hydrogen sulfide (Desulfovibrionaceae) and methanogenic archaea (Methanobacteriaceae). The leading pathogenetic mechanism related to intestinal dysbiosis in chronic constipation, can be microbial metabolic abnormalities (metabolic dysbiosis) characterized by altered production of short-chain fatty acid, methane, hydrogen sulfide, tryptophan metabolites and by abnormal bile acid biotransformation. It has been proven that dysbiotic abnormalities of the intestinal microbiome play a role in the pathophysiology of constipation, which allows for the use of prebiotics, probiotics, and synbiotics for effective microbiome-modulating therapy in patients with chronic constipation. The proven role of dysbiotic abnormalities of the intestinal microbiome in the pathophysiology of chronic constipation determines the effectiveness of microbiome-modulating therapy (prebiotics, probiotics, synbiotics) in patients with this syndrome.

Inulin is the most studied preboitic; it is a soluble food fiber that markedly contributes to the regulation of intestinal microbiota, stimulates the growth of beneficial bacteria, and production of anti-inflammatory metabolites. Inulin normalized the intestinal function in patients with chronic constipation increasing the stool frequency, softening the stool, and reducing the intestinal transit time. In addition, inulin modulates the immune response and impacts the absorption of minerals, appetite, and satiety.

Treatment with probiotics is also associated with reduced intestinal transit time, compared to controls. According to a systematic review and meta-analysis of 30 randomized controlled trials, only Bifidobacterium lactis strains (but not other probiotics) significantly increase stool frequencies in chronic constipation in adults. Clinical studies have shown that the targeted probiotic Bifidobacterium lactis HN019 can significantly increase the stool frequencies in patients with low (≤ 3 per week) stool frequency up to 4.7–5.0 per week, reduce the intestinal transit time and the rate of functional gastroenterological symptoms in adults with constipation. Beyond its clinical effects, Bifidobacterium lactis HN019 leads to beneficial changes in intestinal microbiota, significantly increasing the bifidobacteria and decreasing the enterobacteria numbers.

The results of trials confirm the importance of synbiotic correction of dysbiotic microbiota in all patients with constipation to increase stool frequencies and improve fecal consistency, as well as to prevent the chronic disorders associated with constipation. Synbiotics, such as a combination of Bifidobacterium lactis HN019 and inulin, with the properties of both complementary and synergic synbiotic, may have the greatest microbiome-modulating and functional potential to significantly improve clinical outcomes in patients with chronic constipation compared to probiotics or prebiotics used alone.

Хронический запор – глобальная медико-социальная и экономическая проблема ввиду негативного влияния на качество жизни пациентов и увеличения риска развития колоректального рака, сердечно-сосудистых и цереброваскулярных нарушений.

Микробиота кишечника играет важную роль в патогенезе запоров, взаимодействуя с иммунной системой, энтеральной и центральной нервной системой, и представляет собой перспективную терапевтическую мишень. Дисбиоз кишечника у больных с запорами характеризуется сниженной относительной численностью лактат- (Lactobacillaceae, Bifidobacteriaceae) и бутират-продуцирующих бактерий (Lachnospiraceae, Oscillospiraceae) и повышенными уровнями сероводород-продуцирующих бактерий (Desulfovibrionaceae) и метаногенных архей (Methanobacteriaceae). Ведущим патогенетическим механизмом, связанным с дисбиозом кишечника при хроническом запоре, могут быть нарушения микробного метаболизма (метаболический дисбиоз), проявляющиеся изменениями продукции короткоцепочечных жирных кислот, метана, сероводорода, метаболитов триптофана, а также биотрансформации желчных кислот. Доказанная роль дисбиотических изменений микробиоты кишечника в патофизиологии хронического запора обусловливает эффективность микробиом-модулирующей терапии (пребиотиков, пробиотиков, синбиотиков) у пациентов с данным синдромом.

Среди пребиотиков наиболее изучен инулин – растворимое пищевое волокно, оказывающее выраженное влияние на регуляцию кишечной микробиоты, стимулирующее рост полезных бактерий и продукцию противовоспалительных метаболитов. Инулин нормализует функцию кишечника у пациентов с хроническими запорами, увеличивая частоту дефекаций, смягчая консистенцию стула и сокращая время кишечного транзита. Кроме того, инулин модулирует иммунный ответ, влияет на всасывание минералов, аппетит и чувство насыщения.

Прием пробиотиков также связан с сокращением времени кишечного транзита по сравнению с контролем. По данным систематического обзора и метаанализа 30 рандомизированных контролируемых исследований, только штаммы Bifidobacterium lactis (но не другие пробиотики) значимо увеличивали частоту стула при хронических запорах у взрослых. Клинические исследования показали, что таргетный пробиотик Bifidobacterium lactis HN019 значимо повышал частоту дефекации у пациентов с низкой частотой стула (≤ 3 дефекаций в неделю) до 4,7–5,0 раз в неделю, уменьшал время кишечного транзита и снижал частоту функциональных гастроэнтерологических симптомов у взрослых с запором. Помимо клинических эффектов, Bifidobacterium lactis HN019 вызывал благоприятные изменения кишечной микробиоты, значимо увеличивая количество бифидобактерий и снижая численность энтеробактерий.

Данные исследований подтверждают важность синбиотической коррекции дисбиотически измененной микробиоты у всех пациентов, страдающих запорами, с целью увеличения частоты дефекации и улучшения консистенции каловых масс, а также профилактики ассоциированных с запором хронических заболеваний. Синбиотики, такие как комбинация Bifidobacterium lactis HN019 и инулина, проявляющие свойства как комплементарного, так и синергического синбиотика, могут обладать наибольшим микробиом-модулирующим и функциональным потенциалом, позволяющим значительно улучшить клинические результаты у пациентов с хроническим запором по сравнению с пробиотиками или пребиотиками, применяемыми по отдельности.

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