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

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.

Keywords

• chronic pancreatitis
• exocrine pancreatic insufficiency
• intestinal microbiota
• 16s rrna