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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Victoria D. Bets¹, Kseniya M. Achasova^2,3, Mariya A. Borisova⁴, Elena N. Kozhevnikova^1,2,3, and Ekaterina A. Litvinova^2,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

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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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KEY WORDS: IBD, macrophages, pathogens, microbiome, antibiotics, L-fucose, mucin 2

DOI: 10.1134/S0006297922040010

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