seamedМорская медицинаMarine Medicine2413-57472587-7828Research Institute of Industrial and Maritime Medicine of the Federal Medical and Biological Agency10.22328/2413-5747-2023-9-3-24-39seamed-679Research ArticleОбзорыReviewИзменение состава кишечной микробиоты у пациентов с хроническим гепатитом C, неалкогольной жировой болезнью печени на различных стадиях заболеваний печениСhanges in the composition of gut microbiota in patients with chronic hepatitis С, non-alcoholic fatty liver disease at different stages of liver disease: a reviewhttps://orcid.org/0000-0001-7976-1045ЕфремоваНаталья АлександровнаEfremovaNatalya A.

младший научный сотрудник отдела вирусных гепатитов и заболеваний печени

Junior Researcher of viral hepatitis department

efremova_na@list.ruhttps://orcid.org/0000-0001-7836-1883НикифороваАлександра ОлеговнаNikiforofaAlexandra O.

младший научный сотрудник отдела вирусных гепатитов и заболеваний печени

Junior Researcher of viral hepatitis department

alexa-nikiforova@mail.ruhttps://orcid.org/0000-0002-4509-5352ГрешняковаВера АлександровнаGreshnyakovaVera A.

кандидат медицинских наук, руководитель отдела, старший научный сотрудник отдела вирусных гепатитов и заболеваний печени

Cand. of Sci. (Med.), department head, Senior Researcher of Department of viral hepatitis and liver diseases

veramamayeva@gmail.comДетский научно-клинический центр инфекционных болезнейРоссияChildren’s Research and Clinical Center for Infectious DiseasesRussian FederationДетский научно-клинический центр инфекционных болезней; Санкт-Петербургский государственный педиатрический медицинский университетРоссияChildren’s Research and Clinical Center for Infectious Diseases; Saint Petersburg State Pediatric Medical UniversityRussian Federation202320112023932439Copyright © Ефремова Н.А., Никифорова А.О., Грешнякова В.А., 20232023Ефремова Н.А., Никифорова А.О., Грешнякова В.А.Efremova N.A., Nikiforofa A.O., Greshnyakova V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://seamed.elpub.ru/jour/article/view/679ВВЕДЕНИЕ

ВВЕДЕНИЕ. Микробиота кишечника человека представляет собой совокупность микроорганизмов, находящихся в симбиозе с организмом хозяина. Преобладание бактерий типов Bacteroidetes, Firmicutes, Actinobacteria является характерной чертой кишечной микробиоты человека. Однако состав кишечной микробиоты (КМ) подвержен изменению под влиянием ряда факторов. Доказано влияние оси «кишечник–печень» на патогенез многих хронических заболеваний печени различной этиологии как инфекционной, так и метаболической. Вместе с тем в проанализированной литературе данные о взаимосвязи характера изменений КМ и стадии поражения печени весьма противоречивы.

ЦЕЛЬ

ЦЕЛЬ. Обновление и систематизация представлений о характере изменений состава кишечной микробиоты при хроническом гепатите С (ХГС) и неалкогольной жировой болезни печени (НАЖБП) на различных стадиях заболевания.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. Проведен анализ научной литературы, посвященной изменениям КМ при хронических заболеваниях печени с учетом их этиологии и стадии заболевания, в частности при хроническом вирусном гепатите С и НАЖБП. Поиск проводился в базах данных PubMed, Google Scholar, eLIBRARY за 2000–2023 гг. по ключевым словам: кишечная микробиота; микробиота при гепатите С; микробиота при НАЖБП; микробиота при фиброзе печени; прогрессирование фиброза печени. Было проанализировано 60 научных статей, отобрано 42 источника, из которых более 60 % изданы в течение последних пяти лет.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. В обзоре представлены результаты оригинальных исследований, описывающих основные таксономические различия между микробиомами здоровых людей и пациентов с ХГС, осложненных формированием цирроза печени и гепатоцеллюлярной карциномы (ГЦК). Так, у пациентов с вирусным циррозом печени отмечено обеднение кишечных комменсалов Lachnospiraceae и Ruminococcaceae и значительное обогащение Streptococcaceae, Lactobacillaceae и Enterobacteriaceae.

У пациентов с неалкогольным стеатогепатитом (НАСГ) и F > II выявлено обогащение КМ Рhylum Bacteroides и Proteobacteria, Families Lachnospiraceae и Enterobacteriaceae, Genera Blautia и Escherichia при одновременном снижении Prevotella.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Анализ таксономических единиц КМ в описанных ранее исследованиях не выявил значимых различий в зависимости от этиологии основного заболевания. Однако при ХГС отмечалось снижение представителя phylum Firmicutes - Ruminococcaceae в отличие от НАЖБП. Более четкая связь прослеживается в изменении кишечной микробиоты при F(III–IV) независимо от этиологии. Так, при продвинутом фиброзе печени и циррозе печени (ЦП) как ХГС, так и НАЖБП этиологии описано обогащение КМ за счет увеличения phylum Proteobacteria, в частности рода Escherichia и phylum Firmicutes (Blautia, Veillonellaceae). В проанализированных исследованиях при F(III-IV) отмечается обогащение микробиоты благодаря увеличению phylum Bacteroidetes. Относительно рода Prevotella обнаружены противоречивые результаты. Кроме того, приводятся неоднозначные данные относительно родов Lactobacillus, Ruminococcaceae и Bifidobacteria.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ: По результатам проведенного анализа литературы были получены противоречивые данные о составе КМ у пациентов с ХГС и НАЖБП. Возможно, это обусловлено величиной выборок, неоднородностью исходных данных при отборе в исследование пациентов. Прослеживается связь между составом микробиоты и персистирующим воспалительным процессом, выраженным фиброзом печени. КМ отражает не только функциональные нарушения при хронических заболеваниях печени различной этиологии, но и может служить диагностическим индикатором их прогрессирования.

INTRODUCTION

INTRODUCTION. The human gut microbiota is a set of microorganisms that are in symbiosis with the host organism. The predominance of bacteria of Bacteroidetes, Firmicutes, Actinobacteria types is a characteristic feature of human gut microbiota. However, the composition of the gut microbiota is subject to change under the influence of a number of factors. The influence of the gut-liver axis on the pathogenesis of many chronic liver diseases of various etiologies, both infectious and metabolic, has been proven. At the same time, in the analyzed literature, the data on the relationship between the nature of GM changes and the stage of liver damage are quite controversial.

OBJECTIVE

OBJECTIVE. Updating and systematization of ideas about the nature of changes in the composition of intestinal microbiota in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) at different stages of the disease.

MATERIALS AND METHODS

MATERIALS AND METHODS. We analyzed the scientific literature on GM changes in chronic liver diseases with regard to their etiology and disease stage, in particular in chronic viral hepatitis C and NAFLD. The search was conducted in PubMed, Google Scholar, and eLIBRARY databases for 2000-2023 using the following keywords: gut microbiota; microbiota in hepatitis C; microbiota in NAFLD; microbiota in liver fibrosis; liver fibrosis progression. Sixty scientific articles were analyzed and 42 sources were selected, of which more than 60% were published within the last five years.

RESULTS

RESULTS. This review presents the results of original studies describing the main taxonomic differences between the microbiomes of healthy individuals and patients with CHC complicated by the formation of liver cirrhosis and hepatocellular carcinoma (HCC). Thus, patients with viral cirrhosis showed impoverishment of intestinal commensals Lachnospiraceae and Ruminococcaceae and significant enrichment of Streptococcaceae, Lactobacillaceae and Enterobacteriaceae. In patients with non-alcoholic steatohepatitis (NASH) and F>II, enrichment of GM Phylum Bacteroides and Proteobacteria, Families Lachnospiraceae and Enterobacteriaceae, Genera Blautia and Escherichia, with a concomitant decrease of Prevotella was detected.

DISCUSSION

DISCUSSION. The analysis of GM taxonomic units in the previously described studies did not reveal significant differences depending on the etiology of the underlying disease. However, a decrease in the representative of the phylum Firmicutes - Ruminococcaceae was observed in CHC in contrast to NAFLD. A more distinct relationship can be observed in the changes of intestinal microbiota in F(III-IV) irrespective of etiology. Thus, in advanced liver fibrosis and cirrhosis of both CHC and NAFLD etiologies, enrichment of GM has been described due to an increase in phylum Proteobacteria, in particular the genus Escherichia and phylum Firmicutes (Blautia, Veillonellaceae). In the studies analyzed, at F(III-IV), an enrichment of the microbiota is observed due to an increase in the phylum Bacteroidetes. Regarding the genus Prevotella, contradictory results were found. In addition, there are ambiguous data regarding the genera Lactobacillus, Ruminococcaceae and Bifidobacteria.

CONCLUSION

CONCLUSION. Based on the results of the literature review, we obtained contradictory data on GM composition in patients with CHC and NAFLD. This may be due to the size of samples, heterogeneity of initial data during the selection of patients in the study. The relationship between the composition of microbiota and persistent inflammatory process, expressed liver fibrosis is observed. GM reflects not only functional disorders in chronic liver diseases of various etiologies, but can also serve as a diagnostic indicator of their progression.

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