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Role of Mucin 2 Glycoprotein and L-fucose in Interaction of Immunity and Microbiome within the Experimental Model of Inflammatory Bowel Disease

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Abstract

Many factors underlie the development of inflammatory bowel disease (IBD) in humans. In particular, imbalance of microbiota and thinning of the mucosal layer in the large intestine play a huge role. Pathogenic microorganisms also exacerbate the course of diseases. In this research the role of mucin 2 deficiency in the formation of intestinal microflora in the experimental model using the Muc2 gene knockout mice in the presence of Helicobacter spp. was investigated. Also, restorative and anti-inflammatory effect of the dietary L-fucose in the Muc2–/– mice on microflora and immunity was evaluated. For this purpose, bacterial diversity in feces was studied in the animals before and after antibiotic therapy and role of the dietary L-fucose in their recovery was assessed. To determine the effect of bacterial imbalance and fucose on the immune system, mRNA levels of the genes encoding pro-inflammatory cytokines (Tnf, Il1a, Il1b, Il6) and transcription factors of T cells (Foxp3 – Treg, Rorc – Th17, Tbx21 – Th1) were determined in the colon tissue of the Muc2–/– mice. Significant elimination of bacteria due to antibiotic therapy caused decrease of the fucose levels in the intestine and facilitated reduction of the regulatory T cell transcription factor (Foxp3). When the dietary L-fucose was added to antibiotics, the level of bacterial DNA of Bacteroides spp. in the feces of the Muc2–/– mice was partially restored. T regulatory cells are involved in the regulation of inflammation in the Muc2–/– mice. Antibiotics reduced the number of regulatory T cell but did not decrease the inflammatory response to infection. Fucose, as a component of mucin 2, helped to maintain the level of Bacteroides spp. during antibiotic therapy of the Muc2–/– mice and restored biochemical parameters, but did not affect the inflammatory response.

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Abbreviations

CD:

Crohn’s disease

IBD:

inflammatory bowel disease

UC:

ulcerative colitis

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Funding

The work was supported by the State Budget Project no. AAAA-A21-121011990039-2 (acquisition and maintenance of laboratory animals) and by the Russian Science Foundation (grant no. 20-64-47020, analysis of bacteria and immune parameters).

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Correspondence to Ekaterina A. Litvinova.

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Bets, V.D., Achasova, K.M., Borisova, M.A. et al. Role of Mucin 2 Glycoprotein and L-fucose in Interaction of Immunity and Microbiome within the Experimental Model of Inflammatory Bowel Disease. Biochemistry Moscow 87, 301–318 (2022). https://doi.org/10.1134/S0006297922040010

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