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

Bets, Victoria D; Achasova, Kseniya M; Borisova, Mariya A; Kozhevnikova, Elena N.; Litvinova, Ekaterina A.

doi:10.1134/s0006297922040010

Cited by 13 publications

(12 citation statements)

References 56 publications

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“…L‐fucose is an endogenous and exogenous monosaccharide found in mammals that appears to be involved in various biological functions. Previous studies reported the anti‐inflammation of L‐fucose in several systems such as the respiratory, endocrine, and digestive systems 29,30 . L‐fucose could inhibit macrophage cell M1 polarization, nitrogen permease regulator‐like 3 (NPRL3) inflammasome, and release of TNF‐α, IL‐1β, and IL‐6 pro‐inflammation cytokines, thus exerting anti‐inflammatory effect 31 .…”

Section: Discussionmentioning

confidence: 99%

Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus

Wang

et al. 2023

CNS Neurosci Ther

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AimsStatus epilepticus (SE) is the most common neurological emergency in pediatric patients. This study aimed to screen for prognostic biomarkers of SE in the cerebrospinal fluid (CSF) using metabolomics.MethodsUltra‐performance liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry (UPLC‐QTOF‐MS) was conducted to identify prognostic biomarkers in CSF metabolomics by comparing the poor outcome group (N = 13) with the good outcome group (N = 15) of children with SE. Differentially expressed metabolites were identified using Mann–Whitney U test corrected by Benjamini‐Hochberg and partial least squares discriminant analysis (PLS‐DA).ResultsThe PLS‐DA model identified and validated significant metabolic differences between the poor and good outcome groups of children with SE (PLS‐DA with R2Y = 0.992 and Q2 = 0.798). A total of 49 prognosis‐related metabolites were identified. Of these metabolites, 20 including glutamyl‐glutamine, 3‐iodothyronamine, and L‐fucose had an area under the curve (AUC) ≥ 80% in prognostic prediction of SE. The logistic regression model combining glutamyl‐glutamine and 3‐iodothyronamine produced an AUC value of 0.976, with a sensitivity of 0.863 and specificity of 0.956. Pathway analysis revealed that dysregulation of the citrate cycle (TCA) and arginine biosynthesis may contribute to poor SE prognosis.ConclusionsThis study highlighted the prognosis‐related metabolomic disturbances in the CSF of children with SE and identified potential prognostic biomarkers. A prognostic prediction model combining glutamyl‐glutamine and 3‐iodothyronamine with high predictive value was established.

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Section: Discussionmentioning

confidence: 99%

Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus

Wang

et al. 2023

CNS Neurosci Ther

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“…Modulation of microbiota by L-fucose is demonstrated in the model of DSS-induced colitis and seems to be tightly associated with its protective effects, as in antibiotic-treated mice Lfucose does not ameliorate colitis [38]. Supplementation of drinking water with L-fucose in Muc2 −/− mice undergoing antibiotics treatment also does not reduce the inflammatory response, but partially restores the level of Bacteroides spp., and improves some biochemical parameters [39]. Direct effect of L-fucose on macrophages was also demonstrated, L-fucose inhibited macrophage activation and inflammatory cytokine production in vitro [16].…”

Section: Plos Onementioning

confidence: 80%

L-fucose reduces gut inflammation due to T-regulatory response in Muc2 null mice

et al. 2022

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Fucose, the terminal glycan of the intestinal glycoprotein Mucin2, was shown to have an anti-inflammatory effect in mouse colitis models and modulate immune response due to macrophage polarization changes. In this study we evaluated the effect of 0.05% L-fucose supplementation of drinking water on immune parameters in the intestine of homozygous mutant Muc2−/−, compared to Muc2+/+ mice. To get into innate and adaptive immunity mechanisms of gut inflammation, we tested PrkdcSCIDMuc2−/− strain, Muc2 knockout on SCID background, that is characterized by lack of lymphocytes, in comparison with PrkdcSCID mice. We evaluated intestinal cytokine profiling, macrophage and eosinophil infiltration, and expression of Nos2 and Arg1 markers of macrophage activation in all strains. Markers of Th1, Treg and Th17 cells (Tbx21, Foxp3, and Rorc expression) were evaluated in Muc2−/− and Muc2+/+ mice. Both Muc2−/− and PrkdcSCIDMuc2−/− mice demonstrated increased numbers of macrophages, eosinophils, elevated levels of TNFa, GM-CSF, and IL-10 cytokines. In Muc2−/− mice we observed a wide range of pro-inflammatory cytokines elevated, such as IFN-gamma, IL-1b, IL-12p70, IL-6, M-CSF, G-CSF, IL-17, MCP-1, RANTES, MIP1b, MIP2. Muc2−/− mice demonstrated increase of Nos2, Tbx21 and Foxp3 genes mRNA, while in PrkdcSCIDMuc2−/− mice Arg1 expression was increased. We found that in Muc2−/− mice L-fucose reduced macrophage infiltration and IL-1a, TNFa, IFNgamma, IL-6, MCP-1, RANTES, MIP1b levels, decreased Nos2 expression, and induced the expression of Treg marker Foxp3 gene. On the contrary, in PrkdcSCIDMuc2−/− mice L-fucose had no effect on macrophage and eosinophil numbers, but increased TNFa, GM-CSF, IL-12p70, IL-6, IL-15, IL-10, MCP1, G-CSF, IL-3 levels and Nos2 gene expression, and decreased Arg1 gene expression. We demonstrated that anti-inflammatory effect of L-fucose observed in Muc2−/− mice is not reproduced in PrkdcSCIDMuc2−/−, which lack lymphocytes. We conclude that activation of Treg cells is a key event that leads to resolution of inflammation upon L-fucose supplementation in Muc2−/− mice.

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“…IECs in mice with a MUC2 deficiency lack morphologically distinct goblet cells and show a significant loss of the intestinal epithelial mucosal layer, leading to increased penetrability and the spontaneous development of UC (Kang et al, 2022). In Frontiers in Molecular Biosciences frontiersin.org addition, tissue biopsy samples obtained from patients with clinical UC in either the active or remission stage showed indications of significant loss of the intestinal mucosal mucus layer, which indicated reductions in the number of goblet cells and MUC2 secretion, leading to the loss of the intestinal epithelial mucus layer, which is one of the pathological mechanisms of UC (Bets et al, 2022).…”

Section: Pathophysiological Changes In Uc Mucosal Injury Abnormalitie...mentioning

confidence: 99%

Molecular regulation after mucosal injury and regeneration in ulcerative colitis

Zheng

Duan

Wen

et al. 2022

Front. Mol. Biosci.

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Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease with a complex etiology. Intestinal mucosal injury is an important pathological change in individuals with UC. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5+) intestinal stem cells (ISCs) exhibit self-renewal and high differentiation potential and play important roles in the repair of intestinal mucosal injury. Moreover, LGR5+ ISCs are intricately regulated by both the Wnt/β-catenin and Notch signaling pathways, which jointly maintain the function of LGR5+ ISCs. Combination therapy targeting multiple signaling pathways and transplantation of LGR5+ ISCs may lead to the development of new clinical therapies for UC.

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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

Cited by 13 publications

References 56 publications

Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus

Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus

L-fucose reduces gut inflammation due to T-regulatory response in Muc2 null mice

Molecular regulation after mucosal injury and regeneration in ulcerative colitis

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