Microbiome of the Initial Small Intestine in Patients With Severe Acute Pancreatitis: a Pilot Study
https://doi.org/10.23934/2223-9022-2025-14-1-132-140
Abstract
Disruption of intestinal homeostasis is a leading factor in the pathogenesis and progression of systemic inflammation in patients with acute severe pancreatitis. The development of systemic complications occurs due to both mesenteric hypoperfusion and dysregulation of intestinal motility, as well as destruction of the intestinal barrier, with translocation of bacterial bodies and their substrates. This increases the risk of developing multiple organ failure and increased mortality. With the advent of high-throughput sequencing methods for microbiome samples, for example, in the 16S rRNA format, the possibilities for studying the structure of microbial communities have expanded significantly. In this regard, there is increasing evidence of the relationship between human health and the microflora inhabiting various parts of the body.
AIM OF THE STUDY. Description of the microbiota composition of the initial sections of the small intestine in patients with severe acute pancreatitis.
MATERIAL AND METHODS. The study included 7 patients with a diagnosis of severe acute pancreatitis (6 men, 1 woman), the average age was 54.1±14.4 years. Patients were divided into two groups. Group 1 (n=4) included patients admitted on the 2nd–4th day from the onset of a pain attack. Group 2 (n=3) included patients admitted no later than 24 hours from the onset of the disease. The bacterial composition of jejunal swab samples was studied using 16S RNA sequencing. The severity of the condition was assessed using the integral APACHE II, SOFA, SAPS II scales. In patients of the main group, APACHE II was score 22±2.83, SOFA was score 6.8±0.5, SAPS II was score 32.9±6.4, in patients of the comparison group, APACHE II was score 18.0±3.7, SOFA was score 4.0±2.6, SAPS II was score 24.4±5.0.
The material was collected at the time of insertion of a sterile multifunctional intestinal catheter behind the Treitz ligament, no later than 6 hours after admission to the intensive care unit. At the time of material collection, the patients did not receive antibacterial therapy or enteral nutrition.
RESULTS. More severe disease was associated with reduced representation of Nesseria species in the microbiome mucosa and parvimonas micra, inhabiting the mucosal layer, as well as Megasphaera micronuciformis. The proportion of the genera Streptococcus (species S. rubneri / parasanguinis / australis) and Actinomyces and a number of genera from the Enterobacteriaceae family in such patients was, on the contrary, higher.
Keywords
About the Authors
V. V. KiselyovRussian Federation
Vladimir V. Kiselyov - Candidate of Medical Sciences, Leading Researcher, Department of Emergency Surgery, Endoscopy and Intensive Care, N.V. Sklifosovsky Research Institute for Emergency Medicine.
Bolshaya Sukharevskaya Sq. 3, Moscow, 129090
S. I. Koshechkin
Russian Federation
Stanislav I. Koshechkin - Candidate of Biological Sciences, Director for Science, Nobias Technologies.
Berezovaya Alley Str., 14B, bldg. 2, pom. 2/4, Moscow, 127273
A. V. Kurenkov
Russian Federation
Alexey V. Kurenkov - Physician and Endoscopist, Endoscopy and Intraluminal Surgery Department, N.V. Sklifosovsky Research Institute for Emergency Medicine.
Bolshaya Sukharevskaya Sq. 3, Moscow, 129090
V. E. Odintsova
Russian Federation
Vera E. Odintsova - Head of Analysis Department, Nobias Technologies.
Berezovaya Alley Str., 14B, bldg. 2, pom. 2/4, Moscow, 127273
M. S. Zhigalova
Russian Federation
Maria S. Zhigalova - Candidate of Medical Sciences, Senior Researcher, Department of Emergency Surgery, Endoscopy and Intensive Care, N.V. Sklifosovsky Research Institute for Emergency Medicine.
Bolshaya Sukharevskaya Sq. 3, Moscow, 129090
A. V. Tyakht
Russian Federation
Aleksandr V. Tyakht - Candidate of Biological Sciences, Research Fellow, Institute of Gene Biology Russian Academy of Sciences.
Vavilova Str., 34/5, Moscow, 119334
S. S. Petrikov
Russian Federation
Sergey S. Petrikov - Corresponding Member of the RAS, Professor, Doctor of Medical Sciences, Director of N.V. Sklifosovsky Research Institute for Emergency Medicine, Head of the N.D. Yushchuk Department of Anesthesiology, Resuscitation and Emergency Medicine of the Scientific and Educational Institute of Continuous Professional Education, Russian University of Medicine.
Bolshaya Sukharevskaya Sq. 3, Moscow, 129090; Dolgorukovskaya, St. 4, Moscow, 127006
P. A. Yartsev
Russian Federation
Pyotr A. Yartsev - Professor, Doctor of Medical Sciences, Head of the Scientific Department of Emergency Surgery, Endoscopy and Intensive Care, N.V. Sklifosovsky Research Institute for Emergency.
Bolshaya Sukharevskaya Sq. 3, Moscow, 129090
References
1. Dibirov MD, Isaev AI, Djadjiev AB, Ashimova AI, Ataev T. Role of correction of the syndrome of intestinal failure and abdominal hypertension in the prevention of infection of pancreatic necrosis. Pirogov Russian Journal of Surgery. 2016;(8):67 72. (In Russ.) https://doi.org/10.17116/hirurgia2016867-72
2. Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I, et al. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr. 2018;57(1):1–24. PMID: 28393285 https://doi.org/10.1007/s00394-017-1445-8
3. Yu LC. Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis. J Biomed Sci. 2018;25(1):79. PMID: 30413188 https://doi.org/10.1186/s12929-018-0483-8
4. Yu LC, Wang JT, Wei SC, Ni YH. Host-microbial interactions and regulation of intestinal epithelial barrier function: From physiology to pathology. World J Gastrointest Pathophysiol. 2012;3(1):27–43. PMID: 22368784 https://doi.org/10.4291/wjgp.v3.i1.27
5. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16(6):341–352. PMID: 27231050 https://doi.org/10.1038/nri.2016.42
6. Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016;165(6):1332–1345. PMID: 27259147 https://doi.org/10.1016/j.cell.2016.05.041.
7. Grootjans J, Lenaerts K, Buurman WA, Dejong CH, Derikx JP. Life and death at the mucosal-luminal interface: New perspectives on human intestinal ischemia-reperfusion. World J Gastroenterol. 2016;22(9):2760–2770. PMID: 26973414 https://doi.org/10.3748/wjg.v22.i9.2760
8. Ji Y, Luo X, Yang Y, Dai Z, Wu G, Wu Z. Endoplasmic reticulum stress-induced apoptosis in intestinal epithelial cells: a feed-back regulation by mechanistic target of rapamycin complex 1 (mTORC1). J Anim Sci Biotechnol. 2018;9:38. PMID: 29744053 https://doi.org/10.1186/s40104-018-0253-1
9. Schellekens DH, Hundscheid IH, Leenarts CA, Grootjans J, Lenaerts K, Buurman WA, et al. Human small intestine is capable of restoring barrier function after short ischemic periods. World J Gastroenterol. 2017;23(48):8452–8464. PMID: 29358855 https://doi.org/10.3748/wjg.v23.i48.8452
10. Manohar M, Verma AK, Venkateshaiah SU, Sanders NL, Mishra A. Pathogenic mechanisms of pancreatitis. World J Gastrointest Pharmacol Ther. 2017;8(1):10–25. PMID: 28217371 https://doi.org/10.4292/wjgpt.v8.i1.10
11. Lin R, Chen F, Wen S, Teng T, Pan Y, Huang H. Interleukin-10 attenuates impairment of the blood-brain barrier in a severe acute pancreatitis rat model. J Inflamm (Lond). 2018;15:4. PMID: 29497350 https://doi.org/10.1186/s12950-018-0180-0
12. Sertaridou E, Papaioannou V, Kolios G, Pneumatikos I. Gut failure in critical care: old school versus new school. Ann Gastroenterol. 2015;28(3):309–322. PMID: 26130136
13. Reintam Blaser A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, De Waele J, et al. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Med. 2012;38(3):384–394. PMID: 22310869 https://doi.org/10.1007/s00134-011-2459-y
14. Schmidt PN, Roug S, Hansen EF, Knudsen JD, Novovic S. Spectrum of microorganisms in infected walled-off pancreatic necrosis – impact on organ failure and mortality. Pancreatology. 2014;14(6):444–449. PMID: 25266641 https://doi.org/10.1016/j.pan.2014.09.001
15. Xiao H, Huang JH, Zhang XW, Ahmed R, Xie QL, Li B, et al. Identification of potential diagnostic biomarkers of acute pancreatitis by serum metabolomic profiles. Pancreatology. 2017;17(4):543–549. PMID: 28487129 https://doi.org/10.1016/j.pan.2017.04.015.
16. Yu S, Xiong Y, Fu Y, Chen G, Zhu H, Mo X, et al. Shotgun metagenomics reveals significant gut microbiome features in different grades of acute pancreatitis. Microb Pathog. 2021;154:104849. PMID: 33781869 https://doi.org/10.1016/j.micpath.2021.104849.
17. Andrianova NV, Popkov VA, Klimenko NS, Tyakht AV, Baydakova GV, Frolova OY, et al. Microbiome-Metabolome Signature of Acute Kidney Injury. Metabolites. 2020;10(4):142. PMID: 32260384 https://doi.org/10.3390/metabo10040142
18. Efimova D, Tyakht A, Popenko A, Vasilyev A, Altukhov I, Dovidchenko N, et al. Knomics-Biota – a system for exploratory analysis of human gut microbiota data. BioData Min. 2018;11:25. PMID: 30450127 https://doi.org/10.1186/s13040-018-0187-3
19. Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581–583. PMID: 27214047 https://doi.org/10.1038/nmeth.3869
20. Horton NJ, Kleinman K. Using R and RStudio for Data Management, Statistical Analysis, and Graphics. New York: ImprintChapman and Hall/CRC; 2015. https://doi.org/10.1201/b18151
21. Aitchison J. The Statistical Analysis of Compositional Data. London: Chapman and Hall; 1986. https://doi.org/10.1007/978-94-009-4109-0
22. Gloor GB, Macklaim JM, Pawlowsky-Glahn V, Egozcue JJ. Microbiome Datasets are Compositional: and This is Not Optional. Front Microbiol. 2017;8:2224. PMID: 29187837 https://doi.org/10.3389/fmicb.2017.02224
23. Palarea-Albaladejo J, Martín-Fernández JA. ZCompositions — R package for multivariate imputation of left-censored data under a compositional approach. Chemometrics and Intelligent Laboratory Systems. 2015;143:85–96. https://doi.org/10.1016/j.chemolab.2015.02.019.
24. Villmones HC, Haug ES, Ulvestad E, Grude N, Stenstad T, Halland A, et al. Species Level Description of the Human Ileal Bacterial Microbiota. Sci Rep. 2018;8(1):4736. PMID: 29549283 https://doi.org/10.1038/s41598-018-23198-5
25. Akshintala VS, Talukdar R, Singh VK, Goggins M. The Gut Microbiome in Pancreatic Disease. Clin Gastroenterol Hepatol. 2019;17(2):290–295. PMID: 30144522 https://doi.org/10.1016/j.cgh.2018.08.045
26. Yu J, Feng Q, Wong SH, Zhang D, Liang QY, Qin Y, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut. 2017;66(1):70–78. PMID: 26408641 https://doi.org/10.1136/gutjnl-2015-309800.
27. Osman KL, Jefferies JMC, Woelk CH, Devos N, Pascal TG, Mortier MC, et al. Patients with Chronic Obstructive Pulmonary Disease harbour a variation of Haemophilus species. Sci Rep. 2018;8(1):14734. PMID: 30282975 https://doi.org/10.1038/s41598-018-32973-3
28. Morton DJ, Hempel RJ, Whitby PW, Seale TW, Stull TL. An invasive Haemophilus haemolyticus isolate. J Clin Microbiol. 2012;50(4):1502–1503. PMID: 22301029 https://doi.org/10.1128/JCM.06688-11
29. Saulnier DM, Riehle K, Mistretta TA, Diaz MA, Mandal D, Raza S, et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology. 2011;141(5):1782–1791. PMID: 21741921 https://doi.org/10.1053/j.gastro.2011.06.072
30. Dong Z, Chen B, Pan H, Wang D, Liu M, Yang Y, et al. Detection of Microbial 16S rRNA Gene in the Serum of Patients With Gastric Cancer. Front Oncol. 2019;9:608. PMID: 31338330 https://doi.org/10.3389/fonc.2019.00608
31. Riegel P, Ruimy R, De Briel D, Prevost G, Jehl F, Bimet F, et al. Corynebacterium argentoratense sp. nov., from the human throat. Int J Syst Bacteriol. 1995;45(3):533–537. PMID: 8590681 https://doi.org/10.1099/00207713-45-3-533.
32. Fernández-Natal I, Sáez-Nieto JA, Rodríguez-Lázaro D, Valdezate-Ramos S, Parras-Padilla T, Medina MJ, et al. Phenotypic, molecular characterization, antimicrobial susceptibility and draft genome sequence of Corynebacterium argentoratense strains isolated from clinical samples. New Microbes New Infect. 2016;10:116–121. PMID: 26933505 https://doi.org/10.1016/j.nmni.2016.01.007
33. Chhatwal GS, Graham R. Streptococcal Diseases. In: Quah SR (ed.). International Encyclopedia of Public Health. 2nd ed. Academic Press, 2017. pp. 87–97. https://doi.org/10.1016/B978-0-12-803678-5.00434-3.
34. Fonkou MDM, Bilen M, Cadoret F, Fournier PE, Dubourg G, Raoult D. Enterococcus timonensis sp. nov., Actinomyces marseillensis sp. nov., Leptotrichia massiliensis sp. nov., Actinomyces pacaensis sp. nov., Actinomyces oralis sp. nov., Actinomyces culturomici sp. nov. and Gemella massiliensis sp. nov., new bacterial species isolated from the human respiratory microbiome. New Microbes New Infect. 2017;22:37–43. PMID: 29556407 https://doi.org/10.1016/j.nmni.2017.12.005.
35. Tønjum T. Neisseriales ord. nov. In: Bergey’s Manual of Systematics of Archaea and Bacteria. John Wiley & Sons, Inc.; Bergey’s Manual Trust, 2015. pp. 1–3. https://doi.org/10.1002/9781118960608.obm00079
36. Dai D, Nanthkumar NN, Newburg DS, Walker WA. Role of oligosaccharides and glycoconjugates in intestinal host defense. J Pediatr Gastroenterol Nutr. 2000;30 Suppl 2:S23–33. PMID: 10749398.
37. Carlstedt-Duke B, Midtvedt T, Nord CE, Gustafsson BE. Isolation and characterization of a mucin-degrading strain of Peptostreptococcus from rat intestinal tract. Acta Pathol Microbiol Immunol Scand B. 1986;94(5):293–300. PMID: 3788570 https://doi.org/10.1111/j.1699-0463.1986.tb03056.x.
38. Shetty SA, Marathe NP, Lanjekar V, Ranade D, Shouche YS. Comparative genome analysis of Megasphaera sp. reveals niche specialization and its potential role in the human gut. PLoS One. 2013;8(11):e79353. PMID: 24260205 https://doi.org/10.1371/journal.pone.0079353
39. Marchandin H, Jumas-Bilak E, Gay B, Teyssier C, Jean-Pierre H, Siméon de Buochberg M, et al. Phylogenetic analysis of some Sporomusa sub-branch members isolated from human clinical specimens: description of Megasphaera micronuciformis sp. nov. Int J Syst Evol Microbiol. 2003;53(Pt 2):547–553. PMID: 12710625 https://doi.org/10.1099/ijs.0.02378-0.
Review
For citations:
Kiselyov V.V., Koshechkin S.I., Kurenkov A.V., Odintsova V.E., Zhigalova M.S., Tyakht A.V., Petrikov S.S., Yartsev P.A. Microbiome of the Initial Small Intestine in Patients With Severe Acute Pancreatitis: a Pilot Study. Russian Sklifosovsky Journal "Emergency Medical Care". 2025;14(1):132-140. (In Russ.) https://doi.org/10.23934/2223-9022-2025-14-1-132-140