Comparative analysis of the intestinal microbiota in patients with exocrine pancreatic insufficiency of various severity
- Authors: Maev I.V.1, Levchenko A.I.1, Galeeva J.S.2, Andreev D.N.1, Osipenko J.V.3, Bordin D.S.1,3,4, Ilyina E.N.2
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Affiliations:
- Yevdokimov Moscow State University of Medicine and Dentistry
- Research Institute for Systems Biology and Medicine
- Loginov Moscow Clinical Scientific Center
- Tver State Medical University
- Issue: Vol 95, No 2 (2023)
- Pages: 130-139
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/132896
- DOI: https://doi.org/10.26442/00403660.2023.02.202056
- ID: 132896
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Abstract
Background. Exocrine pancreatic insufficiency (EPI) is a critical host factor in determining the composition of the gut microbiota. Diseases that cause exocrine insufficiency can affect the gut microbiome, which can potentiate disease progression and complications. To date, the relationship of exocrine insufficiency in various pancreatic (PA) pathologies, in chronic pancreatitis (CP), with dysbiotic changes in the intestinal microbiota (IM) has not been reliably studied. The available data are heterogeneous and contradictory, which determines the need for further research.
Aim. To conduct a comparative analysis of the taxonomic composition of the intestinal microbiota in patients with CP of various etiologies, without or with the presence of EPI of varying severity, as well as patients with severe EPI with a history of surgical intervention (SI) on the pancreas.
Materials and methods. A total of 85 patients were included in the study. Patients were divided into groups according to the severity of EPI: Group 1 (n=16) – patients with CP without EPI; Group 2 (n=11) – patients with CP and mild EPI; Group 3 (n=17) – patients with severe CP and EPI; Group 4 (n=41) – severe EPI in persons with a history of SI on the pancreas. Verification of CP was carried out according to clinical, anamnestic and instrumental data. The degree of EPI was determined by the level of pancreatic elastase-1 (PE-1) feces. Informed consent for the study was obtained for each patient, an anamnesis was collected, physical and laboratory examinations were performed, and a stool sample was obtained. DNA was extracted from each stool sample, the taxonomic composition of BM was determined by sequencing the bacterial 16S rRNA genes, followed by bioinformatic analysis.
Results. We followed the changes in the gut microbiota from a group of patients with CP without EPI to a group with severe EPI, in those who underwent SI. At the level of the phylum, the IM of all groups showed the dominance of Firmicutes, with the lowest representation in the severe EPI group, both with SI and CP, and the growth of the Actinobacteria, Verrucomicrobiota and Fusobacteria types. The differential representation of childbirth varied: in patients with severe EPI and CP, compared with mild, statistically significant genera – Akkermansia, Ruminococcus gauvreauii group and Holdemanella; compared with CP without exocrine insufficiency, Prevotella, Ruminococcus gauvreauii group, Peptostreptococcus and Blautia dominated. The CP group with mild EPI was dominated by the following genera: Lachnospiraceae_ND 2004 group, Faecalitalea, Fusobacterium, Catenibacterium, Roseburia, Atopobium, Cloacibacillus, Clostridium innococum group, Ruminococcus torques group. All groups showed a low diversity of taxa with a predominance of opportunistic flora, including participants in oncogenesis.
Conclusion. The results of the study show that patients with CP of various etiologies and patients with severe EPI who underwent specific intervention on the pancreas have intestinal microbiota dysbiosis, the severity of which is significantly influenced by the degree of EPI.
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##article.viewOnOriginalSite##About the authors
Igor V. Maev
Yevdokimov Moscow State University of Medicine and Dentistry
Email: alevchenko914@gmail.com
ORCID iD: 0000-0001-6114-564X
акад. РАН, д-р мед. наук, проф., зав. каф. пропедевтики внутренних болезней и гастроэнтерологии
Russian Federation, MoscowAnna I. Levchenko
Yevdokimov Moscow State University of Medicine and Dentistry
Author for correspondence.
Email: alevchenko914@gmail.com
ORCID iD: 0000-0003-3184-7426
врач-гастроэнтеролог, ассистент каф. пропедевтики внутренних болезней и гастроэнтерологии
Russian Federation, MoscowJulia S. Galeeva
Research Institute for Systems Biology and Medicine
Email: alevchenko914@gmail.com
ORCID iD: 0000-0001-6304-4607
мл. науч. сотр.
Russian Federation, MoscowDmitry N. Andreev
Yevdokimov Moscow State University of Medicine and Dentistry
Email: alevchenko914@gmail.com
ORCID iD: 0000-0002-4007-7112
канд. мед. наук, доц. каф. пропедевтики внутренних болезней и гастроэнтерологии
Russian Federation, MoscowJulia V. Osipenko
Loginov Moscow Clinical Scientific Center
Email: alevchenko914@gmail.com
ORCID iD: 0000-0002-6254-3233
врач-гастроэнтеролог отд-ния патологии поджелудочной железы и желчных путей
Russian Federation, MoscowDmitry S. Bordin
Yevdokimov Moscow State University of Medicine and Dentistry; Loginov Moscow Clinical Scientific Center; Tver State Medical University
Email: alevchenko914@gmail.com
ORCID iD: 0000-0003-2815-3992
д-р мед. наук, проф. каф. пропедевтики внутренних болезней и гастроэнтерологии, зав. отд-нием патологии поджелудочной железы, желчных путей и верхних отделов пищеварительного тракта, проф. каф. общей врачебной практики и семейной медицины
Russian Federation, Moscow; Moscow; TverElena N. Ilyina
Research Institute for Systems Biology and Medicine
Email: alevchenko914@gmail.com
ORCID iD: 0000-0003-0130-5079
чл.-кор. РАН, проф. РАН, д-р биол. наук, гл. науч. сотр., зам. ген. дир. по научной работе
Russian Federation, MoscowReferences
- Gardner TB, Adler DG, Forsmark CE, et al. ACG Clinical Guideline: Chronic Pancreatitis. Am J Gastroenterol. 2020;115(3):322-39. doi: 10.14309/ajg.0000000000000535
- Löhr JM, Dominguez-Munoz E, Rosendahl J, et al. United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United European Gastroenterol J. 2017;5(2):153-99. doi: 10.1177/2050640616684695
- Ивашкин В.Т., Маев И.В., Охлобыстин А.В., и др. Клинические рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению экзокринной недостаточности поджелудочной железы. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2017;27(2):54-80 [Ivashkin VT, Mayev IV, Okhlobystin AV, et al. Diagnostics and treatment of exocrine pancreatic insufficiency: clinical guidelines of the Russian gastroenterological Association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2017;27(2):54-80 (in Russian)]. doi: 10.22416/1382-4376-2017-27-2-54-80
- Маев И.В., Кучерявый Ю.А., Андреев Д.Н., Бидеева Т.В. Статус питания больных хроническим панкреатитом. Терапевтический архив. 2016;88(2):81-9 [Maev IV, Kucheryavyi YuA, Andreev DN, Bideeva TV. Nutritional status in patients with chronic pancreatitis. Terapevticheskii Arkhiv (Ter. Arkh.). 2016;88(2):81-9 (in Russian)].
- Ammer-Herrmenau C, Pfisterer N, Weingarten MF, Neesse A. The microbiome in pancreatic diseases: Recent advances and future perspectives. United European Gastroenterol J. 2020;8(8):878-85. doi: 10.1177/2050640620944720
- Gesualdo M, Rizzi F, Bonetto S, et al. Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives. J Clin Med. 2020;9(11):3535. doi: 10.3390/jcm9113535
- Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16(6):341-52. doi: 10.1038/nri.2016.42
- Scheithauer TPM, Rampanelli E, Nieuwdorp M, et al. Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes. Front Immunol. 2020;11:571731. doi: 10.3389/fimmu.2020.571731
- Gurung M, Li Z, You H, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020;51:102590. doi: 10.1016/j.ebiom.2019.11.051
- Forte N, Fernández-Rilo AC, Palomba L, et al. Obesity Affects the Microbiota-Gut-Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators. Int J Mol Sci. 2020;21(5):1554. doi: 10.3390/ijms21051554
- Coppola S, Avagliano C, Calignano A, Berni Canani R. The Protective Role of Butyrate against Obesity and Obesity-Related Diseases. Molecules. 2021;26(3):682. doi: 10.3390/molecules26030682
- Dong LN, Wang M, Guo J, Wang JP. Role of intestinal microbiota and metabolites in inflammatory bowel disease. Chin Med J (Engl). 2019;132(13):1610-4. doi: 10.1097/CM9.0000000000000290
- Guan Q. A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. J Immunol Res. 2019;2019:7247238. doi: 10.1155/2019/7247238
- Sun M, Wu W, Liu Z, Cong Y. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J Gastroenterol. 2017;52(1):1-8. doi: 10.1007/s00535-016-1242-9
- Moser G, Fournier C, Peter J. Intestinal microbiome-gut-brain axis and irritable bowel syndrome. Intestinale Mikrobiom-Darm-Hirn-Achse und Reizdarmsyndrom. Wien Med Wochenschr. 2018;168(3-4):62-6. doi: 10.1007/s10354-017-0592-0
- Ивашкин В.Т., Зольникова О.Ю. Синдром раздраженного кишечника с позиций изменений микробиоты. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2019;29(1):68-76 [Ivashkin VT, Zolnikova OYu. Irritable Bowel Syndrome in Terms of Changes in the Microbiota. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(1):68-76 (in Russian)]. doi: 10.22416/1382-4376-2019-29-1-84-92
- Евсютина Ю.В., Ивашкин В.Т. Роль микробиома в развитии заболеваний поджелудочной железы. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2017;27(3):11-7 [Evsyutina YuV, Ivashkin VT. Microbiome role in pancreatic diseases development. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2017;27(3):11-7 (in Russian)]. doi: 10.22416/1382-4376-2017-27-3-11-17
- Brubaker L, Luu S, Hoffman K, et al. Microbiome changes associated with acute and chronic pancreatitis: A systematic review. Pancreatology. 2021;21(1):1-14. doi: 10.1016/j.pan.2020.12.013
- Schepis T, De Lucia SS, Nista EC, et al. Microbiota in Pancreatic Diseases: A Review of the Literature. J Clin Med. 2021;10(24):5920. doi: 10.3390/jcm10245920
- Pan LL, Li BB, Pan XH, Sun J. Gut microbiota in pancreatic diseases: possible new therapeutic strategies. Acta Pharmacol Sin. 2021;42(7):1027-39. doi: 10.1038/s41401-020-00532-0
- Шаликиани Н.В., Бакулин И.Г., Дубинкина В.Б., и др. Особенности состава микробиоты кишечника у пациентов с алкогольным циррозом печени. Терапевтический архив. 2015;87(12):59-65 [Shalikiani NV, Bakulin IG, Dubinkina VB, et al. Specific features of the enteric microbiota composition in patients with alcoholic liver cirrhosis. Terapevticheskii Arkhiv (Ter. Arkh.). 2015;87(12):59-65 (in Russian)]. doi: 10.17116/terarkh2015871259-65
- Frost F, Weiss FU, Sendler M, et al. The Gut Microbiome in Patients With Chronic Pancreatitis Is Characterized by Significant Dysbiosis and Overgrowth by Opportunistic Pathogens. Clin Transl Gastroenterol. 2020;11(9):e00232. doi: 10.14309/ctg.0000000000000232
- Zhou CH, Meng YT, Xu JJ, et al. Altered diversity and composition of gut microbiota in Chinese patients with chronic pancreatitis. Pancreatology. 2020;20(1):16-24. doi: 10.1016/j.pan.2019.11.013
- Frost F, Kacprowski T, Rühlemann M, et al. Impaired Exocrine Pancreatic Function Associates With Changes in Intestinal Microbiota Composition and Diversity. Gastroenterology. 2019;156(4):1010-5. doi: 10.1053/j.gastro.2018.10.047
- Ciocan D, Rebours V, Voican CS, et al. Characterization of intestinal microbiota in alcoholic patients with and without alcoholic hepatitis or chronic alcoholic pancreatitis. Sci Rep. 2018;8:4822. doi: 10.1038/s41598-018-23146-3
- Jandhyala SM, Madhulika A, Deepika G, et al. Altered intestinal microbiota in patients with chronic pancreatitis: implications in diabetes and metabolic abnormalities. Sci Rep. 2017;7:43640. doi: 10.1038/srep43640
- Hamada S, Masamune A, Nabeshima T, Shimosegawa T. Differences in Gut Microbiota Profiles between Autoimmune Pancreatitis and Chronic Pancreatitis. Tohoku J Exp Med. 2018;244(2):113-7. doi: 10.1620/tjem.244.113
- Bell ME, Bernard KA, Harrington SM, et al. Lawsonella clevelandensis gen. nov., sp. nov., a new member of the suborder Corynebacterineae isolated from human abscesses. Int J Syst Evol Microbiol. 2016;66(8):2929-35. doi: 10.1099/ijsem.0.001122
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