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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


Victoria D. Bets1, Kseniya M. Achasova2,3, Mariya A. Borisova4, Elena N. Kozhevnikova1,2,3, and Ekaterina A. Litvinova2,a*

1Novosibirsk State Agrarian University, 630039 Novosibirsk, Russia

2Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia

3Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

4Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

* To whom correspondence should be addressed.

Received November 10, 2021; Revised February 24, 2022; Accepted February 24, 2022
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.
KEY WORDS: IBD, macrophages, pathogens, microbiome, antibiotics, L-fucose, mucin 2

DOI: 10.1134/S0006297922040010