The protective effect of Lactobacillus versus 5-aminosalicylic acid in ulcerative colitis model by modulation of gut microbiota and Nrf2/Ho-1 pathway

Life Sci. 2020 Sep 1:256:117927. doi: 10.1016/j.lfs.2020.117927. Epub 2020 Jun 8.

Abstract

Aims: Ulcerative colitis (UC) has many complications, from colonic damage to colorectal cancer. The mystery of both etiology and effective treatment of UC still challenging process. The role of gut microbiota in UC is still unclear. In the current study we compare the difference in gut microbiota abundance in both UC and normal colon besides the therapeutic effect of Lactobacillus spp. in treating UC versus the standard drug.

Materials and methods: The experimental panel included five group of rats; normal control, UC diseased rats, sterilizing rats, ASA treated and Lactobacillus treated. The change in the microbiota abundance was investigated using conventional and real time PCR. In parallel, clinical evaluation of UC and macroscopic examination scoring was also done. Colonic oxidants/antioxidant stress biomarkers; MDA, GSH, catalase, myeloperoxidase activity, and SOD activity were assessed. Colon Nrf2, HO-1 contents and TNF-α was evaluated.

Key findings: The current study revealed a significant difference in the relative abundance of microbiota where, UC is associated with massive increase of E. coli and Fusobacterium spp., while enormous decrease in Bifidobacteria spp. in contrast with negative control. Both 5-ASA and Lactobacillus show a significant amelioration of all antioxidant enzymes and marked decline of inflammatory and oxidative stress markers. Both Lactobacillus and 5-ASA show significant increase of NrF2 and HO-1 and marked decrease of TNF-α.

Significance: Lactobacillus spp. exerted a beneficial effect on the inflammation, oxidative stress and the symbiosis of gut microbiota that improve structural intestinal defect and promote healing in UC.

Keywords: 5-aminosalicylic acid; Acetic acid; Colitis; Lactobacillus; Nrf2/Ho-1 pathway.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Colitis, Ulcerative / metabolism*
  • Escherichia coli
  • Fusobacterium
  • Gastrointestinal Microbiome / drug effects*
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Inflammation / metabolism
  • Lactobacillus / drug effects*
  • Male
  • Mesalamine / pharmacology*
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • Protective Agents
  • Tumor Necrosis Factor-alpha
  • Mesalamine
  • Heme Oxygenase-1