Цель обзора литературы

gastro-j

Российский журнал гастроэнтерологии, гепатологии, колопроктологии

Russian Journal of Gastroenterology, Hepatology, Coloproctology

1382-43762658-6673

«Gastro» LLC

10.22416/1382-4376-2019-29-2-12-22

gastro-j-350

Research Article

ОБЗОРЫ

REVIEWS

Перспективы использования методов коррекции микробиоты при терапии воспалительных заболеваний кишечника

Prospects of Using Microbiota Correction Methods in the Treatment of Inflammatory Bowel Disease

Акиньшина

А. И.

Akinshina

A. I.

аналитик

Analyst

akinshina@cspmz.ru

Смирнова

Д. В.

Smirnova

D. V.

кандидат химических наук, аналитик

Cand. Sci. (Chem.), Analyst

Загайнова

А. В.

Zagainova

A. V.

кандидат биологических наук, зав. лабораторией санитарной бактериологии и паразитологии

Cand. Sci. (Biol.), Head of the Laboratory for Sanitary Bacteriology and Parasitology

milkbacterialab@list.ru

Макаров

В. В.

Makarov

V. V.

кандидат биологических наук, аналитик

Cand. Sci. (Biol.), Analyst

Юдин

С. М.

Yudin

S. M.

доктор медицинских наук, профессор, директор

Dr. Sci. (Med.), Prof., Director

ФГБУ «Центр стратегического планирования и управления медико-биологическими рисками здоровью» Министерства здравоохранения Российской ФедерацииРоссияCentre for Strategic Planning and Management of Biomedical Health RisksRussian Federation

2019

15052019

2921222

2019

Акиньшина А.И., Смирнова Д.В., Загайнова А.В., Макаров В.В., Юдин С.М.

Akinshina A.I., Smirnova D.V., Zagainova A.V., Makarov V.V., Yudin S.M.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.gastro-j.ru/jour/article/view/350

Цель обзора литературы

Цель обзора литературы.Рассмотреть основные методы коррекции микробиоты (антибиотикотерапия, назначение пробиотиков, пребиотиков, метабиотиков и фекальная трансплантация) при воспалительных заболеваниях кишечника, а также проанализировать результаты клинических исследований данных методов.Основные положения. Воспалительные заболевания кишечника (ВЗК) представляют собой группу хронических заболеваний невыясненной этиологии. Ранее для определения состава микробиоты применяли в основном бактериологические методы, которые основывались на выделении чистой культуры бактерий. Однако такие методы не давали полной информации о составе микробиоты. В последние годы предпочтение отдают более точным и быстрым молекулярно-генетическим методам, что позволило более детально изучить не только ключевые механизмы воздействия микробиоты на кишечник при болезни Крона (БК) и язвенном колите (ЯК), но и влияние микробных метаболитов на их патогенез. В данном обзоре рассмотрены основные метаболиты микробиоты и их роль в регуляции барьерной функции кишечника. Актуальным направлением является разработка персонифицированных подходов к терапии и поддержанию ремиссии при ВЗК, в том числе на основании методов коррекции микробного состава: назначение пробиотиков, пребиотиков, метабиотиков и фекальная трансплантация.

Заключение

Заключение.Применение про-, пре- и метабиотиков может способствовать повышению эффективности терапевтических схем и значительному улучшению качества жизни пациентов с хроническими воспалительными заболеваниями кишечника. Применения антибиотиков и ФТ при ВЗК служит предметом оживленных дискуссий и споров. На данный момент не до конца выяснена безопасность данных методов, поэтому крайне важно продолжать исследования их влияния на клиническое состояние пациентов.

Aim

Aim. The present article examines key methods of microbiota correction (antibiotic therapy; pro-, pre- and metabiotic therapy; faecal microbiota transplantation) used in treating inflammatory bowel disease, as well as compares the clinical trial results of these methods.

Key findings

Key findings. Inflammatory bowel disease (IBD) is an umbrella term used to describe a group of chronic diseases of unknown aetiology. In the past, bacteriological methods based on the isolation of a pure bacterial culture were used to determine the microbiota composition. However, such methods did not provide complete information on the microbiota composition. In recent years, preference has been given to more accurate and faster molecular genetic methods allowing a more detailed study of the key mechanisms by which microbiota affects the intestine in Crohn’s disease (CD) and ulcerative colitis (UC), as well as of the effect of microbial metabolites on their pathogenesis. The article provides an overview of main microbiota metabolites and their role in regulating the intestinal barrier func

tion

tion. One of the current issues consists in the development of personalised approaches to therapy and remission maintenance in IBD, including via methods for correcting the microbial composition: probiotic, prebiotic and metabiotic therapy, as well as faecal microbiota transplantation.

Conclusion

Conclusion. The use of probiotics, prebiotics, and metabiotics can enhance the effectiveness of therapeutic regimens and significantly improve the quality of life of patients with chronic IBD. The use of antibiotics and faecal microbiota transplantation in treating IBD is the subject of extensive discussion and debate. The safety of these methods has not been confirmed so far; therefore, it is vital to continue studying their influence on the clinical condition of patients.

микробиотавоспалительные заболевания кишечника (ВЗК)болезнь Кронаязвенный колитпробиотикиантибиотикифекальная трансплантация

microbiotainflammatory bowel disease (IBD)Crohn’s diseaseulcerative colitisprobioticsantibioticsfaecal microbiota transplantation

References1

Packey C.D., Sartor R.B. Interplay of commensal and pathogenic bacteria, genetic mutations, and immunoregulatory defects in the pathogenesis of inflammatory bowel diseases. Journal of internal medicine. 2008;263(6):597–606.

Кузнецова Г.Г. О стадиях нарушения биоценоза кишечника при хронических колитах. Сов. Мед. 1972;11:67

Kuznetsova G.G. The stages of intestinal biocenosis disorders in chronic colitis. Modern medicine, 1972;11:67 (In Rus.)

Bernstein C.N., Robert M.E., Eysselein V.E. Rectal substance P concentrations are increased in ulcerative colitis but not in Crohn’s disease. American Journal of Gastroenterology. 1993;88(6).

Cummings J.H., Macfarlane G.T., Macfarlane S. Intestinal bacteria and ulcerative colitis. Current issues in intestinal microbiology. 2003;4(1):9–20.

Парфенов А.И. Энтерология. Руководство для врачей. М., Медицинское информационное агентство (МИА); 2009:880

Parfenov A.I. Enterology: a guide for doctors. Medical Information Agency. Мoscow. 2009: 880 (In Rus.)

Максимов В.И., Родоман В.Е. Кислотность кишечника как защитный фактор организма хозяина. Микробиология. 1998;4:96

Maksimov V.I., Rodoman V.E. Intestinal Acidity as a protective factor in the host organism. Microbiology. 1998;4:96 (In Rus.)

Eckburg P.B., Bik E.M., Bernstein C.N., Relman D.A. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635–8.

Frank D.N., Amand A.L., Feldman R.A., Boedeker E.C. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceedings of the National Academy of Sciences. 2007;104(34):13780–5.

Sokol H., Pigneur B., Watterlot L., Lakhdari O., Bermudez-Humaran L.G. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proceedings of the National Academy of Sciences 2008;105(43):16731–6.

Малов В.А., Бондаренко В.М., Пак С. Г. Clostridium difficile в патологии человека. Журн. микробиол. 1996;1:91–96

Malov V.A., Bondarenko V.M., Pak S.G. Role of Clostridium difficile in human pathology. Microbiology. 1996;1:91–96 (In Rus.)

Steffen E.K., Berg. R.D. Relationship between cecal population levels of indigenous bacteria and translocation to the mesenteric lymph nodes. Infection and Immunity. 1983;39(3):1252–9.

Caradonna L., Amati L., Magrone T., Pellegrino N.M., Jirillo E., Caccavo D. Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance J Endotoxin Res. 2000;6(3):205–14.

Davie J.R. Inhibition of histone deacetylase activity by butyrate. The Journal of nutrition. 2003;133(7):2485–93.

Thangaraju M., Gopal E., Martin P.M., Ananth S., Smith S.B. et al. SLC5A8 Triggers Tumor Cell Apoptosis through Pyruvate-Dependent Inhibition of Histone Deacetylases. Cancer Research. 2006;66(24):11560–4.

Singh N., Thangaraju M., Prasad P.D., Martin P.M. et al. Blockade of Dendritic Cell Development by Bacterial Fermentation Products Butyrate and Propionate through a Transporter (Slc5a8)-dependent Inhibition of Histone Deacetylases. Journal of Biological Chemistry. 2010;285(36):27601–8.

Montezuma D., Henrique R.M.F., Jeronimo C. Altered Expression of Histone Deacetylases in Cancer. Crit Rev Oncog. 2015;20(1–2):19–34.

West A.C., Johnstone. New and emerging HDAC inhibitors for cancer treatment. The Journal of Clinical Investigation. 2014;124(1):30–9.

Macfarlane S., Macfarlane G.T. Regulation of shortchain fatty acid production. Proceedings of the Nutrition Society. 2003;62(1):67–72.

Li H., Myeroff L., Smiraglia D., Romero M.F., Pretlow T.P. et al. SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proceedings of the National Academy of Sciences. 2003;100(1 4):8412–7.

Kim M., Kim C.H. Regulation of humoral immunity by gut microbial products. Gut microbes. 2017;8(4):392–9.

Hasegawa S., Hiramatsu T., Ichimura A., Kimura I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015;7(4):2839–49.

Dai Z.-L., Wu G., Zhu W.-Y. Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci. 2011;16(1):1768–86.

Macfarlane G.T., Allison C., Gibson S.A.W., Cummings J.H. et al. Contribution of the microflora to proteolysis in the human large intestine. Journal of Applied Microbiology. 1988;64(1):37–46.

Polan C., McNeill J., Tove S. Biohydrogenation of unsaturated fatty acids by rumen bacteria. Journal of Bacteriology. 1964;88(4):1056–64.

Fennema D., Phillips I.R., Shephard E.A. Trimethylamine and trimethylamine N-oxide, a flavin-containing monooxygenase 3 (FMO3)-mediated host-microbiome metabolic axis implicated in health and disease.Drug Metabolism and Disposition. 2016;44(11):1839–50.

Maruyama T., Miyamoto Y., Nakamura T., Tamai Y., Okada H. et al. Identification of membrane-type receptor for bile acids (M-BAR). Biochemical and biophysical research communications. 2002;298(5):714–9.

Kawamata Y., Fujii R., Hosoya M., Harada M., Yoshida H. et al. AG protein-coupled receptor responsive to bile acids. Journal of Biological Chemistry. 2003;278(11):9435–40.

de Groot P.F., Belzer C., Aydin O., Levin E., Levels J.H. et al. Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study. PloS one. 2017;12(12).

Murri M., Leiva I., Gomez-Zumaquero J.-M., Tinahones F.J., Cardona F. et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC medicine. 2013;1(11):46.

Turnbaugh P.J., Ley R.E., Mahowald M.A., Magrin, V., Mardis E.R., Gordon J.I. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027.

Lamas B., Richard M.L., Leducq V., Pham H.-P., Michel M.-L. et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligand. Nature medicine. 2016;22(6):598.

Nikolaus S., Schulte B., Al-Massad N., Thieme F, Schulte D.M., Bethge J. et al. Increased tryptophan metabolism is associated with activity of inflammatory bowel diseases. Gastroenterology. 2017;153(6):1504–6.

Maccaferri S., Vitali B., Klinder A., Kolida S. et al. Rifaximin modulates the colonic microbiota of patients with Crohn’s disease: an in vitro approach using a continuous culture colonic model system. J Antimicrob Chemother. 2010;65(2556):65.

Farrell R.J., LaMont J.T. Microbial factors in inflammatory bowel disease. Gastroenterol Clin North Am. 2002;31(41):62.

Sartor R.B. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126(1620):33.

Isaacs K.L., Sartor R.B. Treatment of inflammatory bowel disease with antibiotics. Gastroenterol Clin North Am. 2004;33(335):45.

Sartor R.B. Review article: the potential mechanisms of action of rifaximin in the management of inflammatory bowel diseases.Aliment Pharmacol Ther. 2016;43(1):27–36.

Brown C.L., Smith K., Wall D.M., Walker D. Activity of species-specific antibiotics against Crohn’s disease-associated adherent-invasive Escherichia coli. Inflamm Bowel Dis. 2015;21(2372):82.

Di Marco R., Mangano K., Quattrocchi C., Musumeci R. et al. Curative effects of sodium fusidateon the development of dinitrobenzenesulfonic acid-induced colitis in rats. Clin Immunol. 2003;109(266):71.

Wan Y.C., Li T., Han Y.D., Lin H. et al. Effect of pregnane xenobiotic receptor activation on inflammatory bowel disease treated with rifaximin. J Biol Regul Homeost Agents. 2015;29(401):10.

Kolios G., Manousou P., Bourikas L., Notas G. et al. Ciprofloxacin inhibits cytokine-induced nitric oxide production in human colonic epithelium. Eur J Clin Invest. 2006;36(720):29.

Travis S.P., Stange E.F., Lémann M., Oresland T., Bemelman W.A. et al. European evidence-based Consensus on the management of ulcerative colitis: Current management. Journal of Crohn’s and Colitis. 2008;2(24):62.

Gan S.I., Beck P.L. A new look at toxic megacolon: an update and review of incidence, etiology, pathogenesis, and management. Am J Gastroenterol. 2003;98(2363):71.

Perencevich M., Burakoff R. Use of antibiotics in the treatment of inflammatory bowel disease. Inflamm Bowel Dis. 2006;12(7):64.

Ruemmele F.M., Veres G., Kolho K.L., Griffiths A. et al. European Crohn’s and Colitis Organisation; European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohn’s Colitis. 2014;8:1179–1207.

Lev-Tzion R., Ledder O., Shteyer E., Uhlig H.H. et al. Oral vancomycin and gentamicin for treatment of very early onset inflammatory bowel disease. Digestion. 2017;95(310):13.

Sood A., Midha V., Makharia G.K., Ahuja V., Singal D., Goswami P., Tandon R.K. et al. The probiotic preparation, VSL# 3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clinical Gastroenterology and Hepatology. 2009;7(11):1202–9.

Tursi А., Brandimarte G., Papa A., Giglio A. et al. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL# 3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Amer J Gastroenterol. 2010;105(10):2218–27.

Thomas D.W., Greer F.R. Probiotics and prebiotics in pediatrics. Pediatrics. 2010;126(6):1217–31.

Mack D.R., Ahrne S., Hyde L., Wei S., Hollingsworth M.A. et al. Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut. 2003;52(6):827–33.

Caballero-Franco C., Keller K., De Simone C., Chadee K. The VSL# 3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2007;292(1):315–22.

Stephani J., Radulovic K., Niess J.H. Gut microbiota, probiotics and inflammatory bowel disease. Archivum immunologiae et therapiae experimentalis. 2011;59(3):161–77.

Macho Fernandez E., Pot B., Grangette C. Beneficial effect of probiotics in IBD: are peptidogycan and NOD2 the molecular key effectors? Gut Microbes. 2011;2(5):280–6.

Rossland E., Langsrud T., Granum P.E., Sorhaug T. Production of antimicrobial metabolites by strains of Lactobacillus or Lactococcus co-cultured with Bacillus cereus in milk. Int. J. Food Microbiol. 2005;98(2):193–200.

Cadieux P., Burton J., Gardiner G. Lactobacillus strains and vaginal ecology. JAMA. 2002;287(15):1940–1.

Schauber J., Svanholm C., Termén S, Iffland K., Menzel T., Scheppach W. et al. Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways. Gut. 2003;52(5):735–41.

D’Incà R., Barollo M., Scarpa M., Grillo A.R., Brun P. et al. Rectal administration of Lactobacillus casei DG modifies flora composition and Toll-like receptor expression in colonic mucosa of patients with mild ulcerative colitis. Dig. Dis. Sci. 2011;56(4):1178–87.

Tursi A., Brandimarte G., Giorgetti G.M., Forti G., Modeo M.E., Gigliobianco A. Low-dose balsalazide plus a high-potency probiotic preparation is more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis. Med. Sci. Monit. 2004;10(11):1126–31.

Zocco M.A., Dal Verme L.Z., Cremonini F., Piscaglia A.C., Nista E.C. et al. Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment. Pharmacol. Ther. 2006;23(11):1567–74.

Ардатская М.Д., Логинов В.А., Минушкин О.Н. Новые возможности диагностики и коррекции микроэкологических нарушений кишечника. Consilium medicum. Гастроэнтерология. 2013;2:51–8

Ardatskaya M.D., Loginov V.A., Minushkin O.N. New possibilities for diagnostics and correction of microecological intestinal disorders. Consilium medicum. Gastroenterology. 2013;2:51–58 (In Rus.)

Павленко В.В., Катаганова Г.А., Александрова С.Б., Кораблина Н.В., Павленко А.Ф. Пробиотики и воспалительные заболевания кишечника: оценка эффективности пробиотического комплекса «Бактистатин» в терапии больных язвенным колитом. Современные проблемы науки и образования. 2015;5

Pavlenko V.V., Kataganova G.A., Aleksandrova S.B., Korablina N.V., Pavlenko A.F. Probiotics and inflammatory bowel disease: effectiveness assessment of the probiotic complex “Baktistatin” in the therapy of patients with ulcer colitis. Modern problems of science and education. 2015;5 (In Rus.)

Ардатская М.Д. Масляная кислота и инулин в клинической практике. Теоретические аспекты и возможности клинического применения. М.: Форте принт; 2014:64.

Ardatskaya M.D. Butyric acid and inulin in clinical practice. Theoretical aspects and clinical applications. Moscow: Forte Print; 2014:64 (In Rus.)

Schultsz C., van den Berg F.M., ten Kate F.W., Tytgat G.N.J., Dankert J. The intestinal mucus layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls. Gastroenterology. 1999;117(5):1089–97.

Gupta P., Andrew H., Kirschner B., Guandalini S. Is lactobacillus GG helpful in children with Crohn’s disease? Results of a preliminary, open-label study.J. Pediatr. Gastroenterol. Nutr. 2000;31(4):453–7.

Bousvaros A., Guandalini S., Baldassano R., Botelho Ch., Evans J. et al. A randomized, double-blind trial of lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease. Inflamm Bowel Diseases. 2005;11(9):833.

Guslandi M., Giollo P., Testoni P.A. Saccharomyces boulardii in maintenance treatment of Crohns disease. Dig. Dis. Sci. 2000;45(7):1462–4.

Rahimi R., Nikfar S., Rahimi F., Behzad E. et al. A meta-analysis on the efficacy of probiotics for maintenance of remission and prevention of clinical and endoscopic relapse in Crohn’s disease. Dig Dis Sci. 2008;53(9):2524–31.

Borthakur A., Gill R.K., Tyagi S., Koutsouris A., Alrefai W.A., Hecht G.A., Ramaswamy K., Dudeja P.K. The probiotic Lactobacillus acidophilus stimulates chloride/hydroxyl exchange activity in human intestinal epithelial cells. J Nutr. 2008;138(7):1355.

Borthakur A., Bhattacharyya S., Kumar A., Anbazhagan A.N., Tobacman J.K., Dudeja PK. Lactobacillus acidophilus Alleviates Platelet-Activating Factor-Induced Inflammatory Responses in Human Intestinal Epithelial Cells. PLoS One. 2013;8(10):e75664.

Meijer B.J., Dieleman L.A. Probiotics in the treatment of human inflammatory bowel diseases: update 2011. Journal of clinical gastroenterology. 2011;45:139–44.

Kassam Z., Lee C.H., Yuan Y., Hunt R.H. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013;108(4):500–8.

van Nood E., Vrieze A., Nieuwdorp M., Fuentes S., Zoetendal E.G., de Vos W.M. et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–15.

Lee C.H., Steiner T., Petrof E.O., Smieja M., Roscoe D., Nematallah A. et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: a randomized clinical trial. JAMA. 2016;315(2):142–9.

Bennet J., Brinkman M. Treatment of ulcerative colitis by implantation of normal colonic flora. The Lancet. 1989;333(8630):164.

Borody T.J., Warren E.F., Leis S., Surace R., Ashman O. Treatment of ulcerative colitis using fecal bacteriotherapy. Journal of clinical gastroenterology. 2003;37(1):42–47.

Kunde S., Pham A., Bonczyk S., Crumb T., Duba M., Conrad H. Jr., Cloney D., Kugathasan S. Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol Nutr. 2013;56:597–601.

Rossen N.G., Fuentes S., van der Spek M.J., Tijssen J.G., Hartman J.H., Duflou A., Löwenberg M. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology. 2015;149:110–8.

Paramsothy S., Kamm M.A., Kaakoush N.O., Walsh A.J., van den Bogaerde J. et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebocontrolled trial. Lancet. 2017;389:1218–28.

Vermeire S., Joossens M., Verbeke K., Wang J., Machiels K. et al. Donor species richness determines faecal microbiota transplantation success in inflammatory bowel disease. J Crohn’s Colitis. 2016;10:387–94.

Vaughn B.P., Vatanen T., Allegretti J.R., Bai A., Xavier R.J., Korzenik J. et al. Increased intestinal microbial diversity following fecal microbiota transplant for active Crohn’s disease. Inflamm Bowel Dis. 2016;22(9):2182–90.

Jeon S.R., Chai J., Kim C., Lee C.H. Current Evidence for the Management of Inflammatory Bowel Diseases Using Fecal Microbiota Transplantation. Curr Infect Dis Rep. 2018;20(8):21.

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