Comparative analysis of the intestinal microbiota in patients with exocrine pancreatic insufficiency of various severity

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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.

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, Moscow

Anna 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, Moscow

Julia S. Galeeva

Research Institute for Systems Biology and Medicine

Email: alevchenko914@gmail.com
ORCID iD: 0000-0001-6304-4607

мл. науч. сотр.

Russian Federation, Moscow

Dmitry 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, Moscow

Julia 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, Moscow

Dmitry 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; Tver

Elena 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, Moscow

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Supplementary files

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2. Fig. 1. Study participants. Division into groups.

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3. Fig. 2. The distribution of participants in study groups by age.

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4. Fig. 3. Ratios of participants in study groups by body mass index.

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5. Fig. 4. The distribution of participants in study groups by body mass index.

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6. Fig. 5. The distribution of pancreatic fecal elastase-1 levels in the study groups.

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7. Fig. 6. Etiology of chronic pancreatitis according to the international classification TIGAR-O.

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8. Fig 7. Etiological factors of surgery according to medical history.

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9. Fig. 8. Heat map of the abundance of prokaryotic organisms in fecal samples of 85 patients with chronic pancreatitis and exocrine pancreatic insufficiency (indicated in green, orange, blue, and pink).

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10. Fig. 9. Taxonomic α-diversity of the intestinal microbiota in the study groups.

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11. Fig. 10. Graph of the similarity of the taxonomic composition (β-diversity) of the intestinal microbiota in patients with chronic pancreatitis and exocrine pancreatic insufficiency, measured using non-metric multidimensional scaling (NMDS) by species diversity (Brea–Certis dissimilarity) using the principle component analyses.

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12. Fig. 11. Graph of the relative abundance of the four most common types of fecal specimens of all patients with chronic pancreatitis and different degrees of exocrine pancreatic insufficiency.

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13. Fig. 12. Visualization of the intestinal microbiota balance in patients with varying degrees of exocrine pancreatic insufficiency using a CoDa-dendrogram (top-10 common families were selected for analysis).

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14. Fig. 13. Analysis of the differential abundance of 16S bacterial amplicons agglomerated at the genus level and associated with groups 1, 2, and 3. The statistical significance level calculated from the analysis results for each differentially abundant genus is displayed to the right and left of the columns.

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15. Fig. 14. Analysis of the differential abundance of 16S bacterial amplicons agglomerated at the genus level and associated with groups 2, 3, and 4. The statistical significance level calculated from the analysis results for each differentially abundant genus is displayed to the right and left of the columns.

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Copyright (c) 2023 Maev I.V., Levchenko A.I., Galeeva J.S., Andreev D.N., Osipenko J.V., Bordin D.S., Ilyina E.N.

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This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 
 


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