Features of dysbiotic changes of the large intestine and indicators of short-chain fatty acids in patients with chronic inflammatory bowel disease depending on the nutritional status

August 19, 2021
856
Resume

Objective: to determine the depth of dysbiotic disorders of the quantitative and qualitative composition of the microflora of the colon, as well as the levels of short-chain fatty acids (SCFA) in patients with chronic inflammatory bowel disease (CIBD), depending on the nosology and the degree of nutritional deficiency.

Materials and methods. We examined 100 patients with CIBD, aged from 19 to 79 years, on average (42.54±1.5) years, including 70 patients with nonspecific ulcerative colitis (NEC), 30 — with Crohn’s disease (CD). According to the degree of nutritional insufficiency, all patients were divided into 3 groups (I — without signs of nutritional insufficiency, II — with mild degree and III — with moderate degree of nutritional insufficiency). All patients underwent general clinical examination, anthropometric measurements, bacteriological examination of feces and chromatography of SCFA in coprofiltrate.

Results. Conducted microbiological studies revealed the presence of profound changes in the qualitative and quantitative composition of the microflora of the colon in 100.0% of patients with CIBD, with a predominance of dysbiosis III (38.0%). The main changes were related to the probable (p<0.001) decrease in the number of main symbionts of the colon microbiocenosis, namely the decrease in the level of bifidobacteria in 89.0% of patients and lactobacilli in 92.0% of patients in the general group of CIBD. Patients with CD and NEC showed a probable decrease in the level of bifidobacteria (86.7 and 90.0%) compared with the healthy individuals (p<0.001). Lactobacilli were reduced in all patients with CD and 88.6% in the NEC group (p<0.001). The dependence of dysbiotic changes in the studied patients on the presence or degree of nutritional insufficiency was revealed. Decompensated form of dysbiosis was more common in patients of group III (50.0%) in contrast to group I, where its frequency was only 26.5%. Decreases in the concentration of bifidobacteria in the contents of the colon in patients of group III were found most often — in 79.3%, while the deficiency of lactobacilli was most often observed in patients of group I (94.7%). In addition, in group III the frequency of yeast-like fungi of the genus Candida was higher (55.2%). When analyzing the relative content of SCFA in coprofiltrate, changes were observed in both the total content and indicators of individual SCFA compared with the healthy individuals, which indicated the inhibition of metabolic activity of normal microflora. It was found that the level of acetic acid (C2) in patients of all three groups (with or without nutritional deficiency) with CIBD was 100.0% reduced compared with the control (p<0.001). In patients with NEC there was a probable increase in levels of propionic acid (C3) in 4.4 times (p<0.05) in groups II and III, and also showed a tendency to a significant decrease in butyric acid (C4), mainly in patients of group III.

Conclusions. Profound changes in the qualitative and quantitative composition of the microflora in the large intestine were identified in all patients with CIBD. The severity of dysbiotic changes increases with increasing severity of nutritional insufficiency, so it is possible to consider severe dysbiosis as a prognostic marker of nutritional status disorders. Divergent deviations from the control of the main metabolites of the colon microbiota can serve as biochemical markers of structural and functional disorders of the intestinal microbiocenosis. Given the above, the determination of the content of SCFA can have diagnostic and prognostic value.

References:

  • 1. Nishida A., Inoue R., Inatomi O. et al. (2018) Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin. J. Gastroenterol., 11(1): 1–10. doi:10.1007/s12328-017-0813-5.
  • 2. Younis N., Zarif R., Mahfouz R. (2020) Inflammatory bowel disease: between genetics and microbiota. Mol. Biol. Rep., 47(4): 3053–3063. doi:10.1007/s11033-020-05318-5.
  • 3. Kaplan G.G., Ng S.C. (2017) Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. Gastroenterology, 152(2): 313–321. doi:10.1053/j.gastro.2016.10.020.
  • 4. Kaplan G.G. (2015) The global burden of IBD: from 2015 to 2025. Nat. Rev. Gastroenterol. Hepatol., 12(12): 720–727. doi:10.1038/nrgastro.2015.150.
  • 5. Lavelle A., Sokol H. (2020) Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol., 17(4): 223–237. doi:10.1038/s41575-019-0258-z.
  • 6. Zhu R., He P., Liu Z. et al. (2021) Editorial: Microbiome in IBD: From Composition to Therapy. Front. Pharmacol., 12: 721992. doi:10.3389/fphar.2021.721992.
  • 7. Glassner K.L., Abraham B.P., Quigley E.M.M. (2020) The microbiome and inflammatory bowel disease. J. Allergy Clin. Immunol., 145(1): 16–27. doi:10.1016/j.jaci.2019.11.003.
  • 8. Rooks M.G., Garrett W.S. (2016) Gut microbiota, metabolites and host immunity. Nat. Rev. Immunol., 16(6): 341–352. doi:10.1038/nri.2016.42.
  • 9. Agus A., Denizot J., Thévenot J. et al. (2016) Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation. Sci. Rep., 6: 19032. doi:10.1038/srep19032.
  • 10. Scott N.A., Andrusaite A., Andersen P. et al. (2018) Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis. Sci. Transl. Med., 10(464): eaao4755. doi:10.1126/scitranslmed.aao4755.
  • 11. Pascal V., Pozuelo M., Borruel N. et al. (2017) A microbial signature for Crohn’s disease. Gut, 66(5): 813–822. doi:10.1136/gutjnl-2016-313235.
  • 12. Louis P., Flint H.J. (2017) Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol., 19(1): 29–41. doi:10.1111/1462-2920.13589.
  • 13. Corrêa-Oliveira R., Fachi J.L., Vieira A. et al. (2016) Regulation of immune cell function by short-chain fatty acids. Clin. Transl. Immunol., 5(4): e73. doi: 10.1038/cti.2016.17.
  • 14. Parada Venegas D., De la Fuente M.K., Landskron G. et al. (2019) Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front. Immunol., 10: 277. doi:10.3389/fimmu.2019.00277.
  • 15. Fernando M.R., Saxena A., Reyes J.L., McKay D.M. (2016) Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages. Am. J. Physiol. Gastrointest. Liver Physiol., 310(10): G822–G831. doi:10.1152/ajpgi.00440.2015.
  • 16. Sun M., Wu W., Liu Z., Cong Y. (2017) Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J. Gastroenterol., 52(1): 1–8. doi:10.1007/s00535-016-1242-9.
  • 17. Franzosa E.A., Sirota-Madi A., Avila-Pacheco J. et al. (2019) Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat .Microbiol., 4(2): 293–305. doi:10.1038/s41564-018-0306-4.