The Role of Glycosylation in Inflammatory Diseases

Alves, Inês; Vicente, Manuel M.; Dias, Adelaide; Gaifem, Joana; Rodrigues, C; Campar, Ana; Pinho, Salomé S.

doi:10.1007/978-3-030-70115-4_13

Cited by 7 publications

(12 citation statements)

References 158 publications

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“…Other auto-reactive antibodies characteristic of SLE include anti-doublestranded DNA (anti-dsDNA) antibodies, anti-Smith (SM) antibodies, and anti-Sjogren's antibodies [4]. The dysregulation of the adaptive immune network in SLE can induce the production of high levels of these antibodies due to abnormal T-and B-cell activation and impaired apoptotic pathways [5]. While the exact pathogenesis underlying the dysregulation of the adaptive immune system in SLE is unknown, it has been postulated that inflammation is the foundation of the disease.…”

Section: Relationship Between Sle the Gut Microbiome And The Immune S...mentioning

confidence: 99%

“…While the exact pathogenesis underlying the dysregulation of the adaptive immune system in SLE is unknown, it has been postulated that inflammation is the foundation of the disease. Current literature suggests the possibility that one primary factor contributing to the onset and progression of inflammatory autoimmune conditions, such as SLE, type I diabetes, and rheumatoid arthritis, is microbiome dysbiosis [5]. This dysbiosis appears to increase bowel permeability, which causes bacterial products to leak out from the gut, resulting in inflammation and, therefore, an overactive immune system.…”

Section: Relationship Between Sle the Gut Microbiome And The Immune S...mentioning

confidence: 99%

“…This dysbiosis appears to increase bowel permeability, which causes bacterial products to leak out from the gut, resulting in inflammation and, therefore, an overactive immune system. In a patient with elevated ANAs and a weak ability to prevent reactivity to self-antigens, a leaky gut may be the final factor leading to the manifestation of the clinical hallmarks of SLE [5].…”

Section: Relationship Between Sle the Gut Microbiome And The Immune S...mentioning

confidence: 99%

“…GALT protects against mucosal pathogens and allows tolerance to self-antigens and commensal bacteria. The gut microbiome is also key in the development of regulatory T cells and helper T cells [5]. Regulatory T cells help regulate the gut's beneficial and pathogenic bacteria.…”

Section: Relationship Between Sle the Gut Microbiome And The Immune S...mentioning

confidence: 99%

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A Scoping Review of the Positive and Negative Bacteria Associated With the Gut Microbiomes of Systemic Lupus Erythematosus Patients

McPhail,

Wu,

Tague

et al. 2024

Cureus

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems of the body. Recent research on the gut microbiota dysbiosis associated with SLE patients has gained traction and warranted further exploration. It has not been determined whether the change in the gut microbiota is a cause of SLE or a symptom of SLE. However, based on the physiological and pathophysiological role of the bacteria in the gut microbiome, as levels of the bacteria rise or fall, symptomatology in SLE patients could be affected. This review analyzes the recent studies that examined the changes in the gut microbiota of SLE patients and highlights the correlations between gut dysbiosis and the clinical manifestations of SLE. A systematic search strategy was developed by combining the terms "SLE," "systemic lupus erythematosus," and "gut microbiome." Biomedical Reference Collection, CINAHL, Medline ProQuest, and PubMed Central databases were searched by combining the appropriate keywords with "AND." Only full-text, Englishlanguage articles were searched. The articles were restricted from 2013 to 2023. Only peer-reviewed controlled studies with both human and animal trials were included in this scoping review. Review articles, non-English articles, editorials, case studies, and duplicate articles from the four databases were excluded.Various species of bacteria were found to be positively or negatively associated with SLE gut microbiomes. Among the bacterial species increased were Clostridium, Lactobacilli, Streptococcus, Enterobacter, and Klebsiella. The bacterial species that decreased were Bifidobacteria, Prevotella, and the Firmicutes/Bacteroidetes ratio. Literature shows that Clostridium is one of several bacteria found in abundance, from pre-disease to the diseased state of SLE. Lachnospiraceae and Ruminococcaceae are both part of the family of butyrate-producing anaerobes that are known for their role in strengthening the skin barrier function and, therefore, may explain the cutaneous manifestations of SLE patients. Studies have also shown that the Firmicutes/Bacteroidetes ratio is significantly depressed, which may lead to appetite changes and weight loss seen in SLE patients. Based on the established role of these bacteria within the gut microbiome, the disruption in the gut ecosystem could explain the symptomatology common in SLE patients. By addressing these changes, our scoping review encourages further research to establish a true causal relationship between the bacterial changes in SLE patients as well as furthering the scope of microbiota changes in other systems and autoimmune diseases.

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Section: Relationship Between Sle the Gut Microbiome And The Immune S...mentioning

confidence: 99%

Section: Relationship Between Sle the Gut Microbiome And The Immune S...mentioning

confidence: 99%

Section: Relationship Between Sle the Gut Microbiome And The Immune S...mentioning

confidence: 99%

Section: Relationship Between Sle the Gut Microbiome And The Immune S...mentioning

confidence: 99%

See 2 more Smart Citations

A Scoping Review of the Positive and Negative Bacteria Associated With the Gut Microbiomes of Systemic Lupus Erythematosus Patients

McPhail,

Wu,

Tague

et al. 2024

Cureus

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“…IBD is characterized as an uncontrolled and vigorous immune response to the gut microbiota which can occur in predisposed individuals. However, the direct roles that the microbiota play in IBD etiology have yet to be fully resolved (5,6), and it has become apparent that the host glycome is a critical factor in IBD onset and progression (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Human gut metagenomes encode diverse GH156 sialidases

Mann

Shekarriz

Surette

2022

Preprint

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The intestinal lining is protected by a mucous barrier composed predominantly of complex carbohydrates. Gut microbes employ an array of glycoside hydrolases (GHs) to liberate mucosal sugars as a nutrient source to facilitate host colonization. Intensive catabolism of mucosal glycans, however, may contribute to barrier erosion, pathogen encroachment and inflammation.Sialic acid is an acidic sugar featured at terminal positions of host glycans. Characterized sialidases from the microbiome belong to the GH33 family, according to CAZy (Carbohydrate Active enZyme) database classification. A 2018 functional metagenomics screen using thermal spring DNA uncovered the founding member of the GH156 sialidase family, which lacks homology to GH33 sialidases and could not be taxonomically assigned. Subsequent structural analysis revealed critical active site residues. We sought to determine if GH156 sialidases are present in the human gut microbiome where they might contribute to mucous erosion.A subset of GH156 sequences from the CAZy database containing key sialidase residues was used to build a Hidden Markov Model. HMMsearch against public databases revealed ∼10X more putative GH156 sialidases than currently recognized by CAZy. Represented phyla include Bacteroidota, Verrucomicrobiota and Firmicutes_A from human microbiomes, all of which play notable roles in carbohydrate fermentation. Genomic analyses suggested that taxa containing GH156-encoding genes may utilize host-glycans. Analyses of metagenomic datasets revealed that GH156s are frequently encoded in metagenomes, with a greater variety and abundance of GH156 genes observed in traditional hunter-gatherer or agriculturalist societies than in industrialized societies, particularly relative to individuals with IBD. A GH156 gene frequently detected in traditional populations was cloned from stool sample DNA and the recombinant protein exhibited sialidase activity with a fluorogenic substrate.ImportanceSialic acids occupy terminal positions of human glycans where they act as receptors for microbes, toxins and immune signaling molecules. Microbial enzymes that remove sialic acids, sialidases, are abundant in the human microbiome where they may contribute to shaping the microbiota community structure or contribute to pathology. Furthermore, sialidases have proven to hold therapeutic potential for cancer therapy. Here we examined the sequence space of a sialidase family of enzymes, GH156, previously unknown to the human gut environment. Our analyses suggest that human populations with disparate dietary practices harbour distinct varieties and abundances of GH156-encoding genes. Furthermore, we demonstrate the sialidase activity of a gut derived GH156. These results expand the diversity of sialidases that may contribute to host glycan degradation and these sequences may have biotechnological or clinical utility.

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A Computational and Chemical Design Strategy for Manipulating Glycan‐Protein Recognition

Zhu,

Geng,

et al. 2024

Advanced Science

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Glycans are complex biomolecules that encode rich information and regulate various biological processes, such as fertilization, host‐pathogen binding, and immune recognition, through interactions with glycan‐binding proteins. A key driving force for glycan‐protein recognition is the interaction between the π electron density of aromatic amino acid side chains and polarized C─H groups of the pyranose (termed the CH–π interaction). However, the relatively weak binding affinity between glycans and proteins has hindered the application of glycan detection and imaging. Here, computational modeling and molecular dynamics simulations are employed to design a chemical strategy that enhances the CH–π interaction between glycans and proteins by genetically incorporating electron‐rich tryptophan derivatives into a lectin PhoSL, which specifically recognizes core fucosylated N‐linked glycans. This significantly enhances the binding affinity of PhoSL with the core fucose ligand and enables sensitive detection and imaging of core fucosylated glycans in vitro and in xenograft tumors in mice. Further, the study showed that this strategy is applicable to improve the binding affinity of GafD lectin for N‐acetylglucosamine‐containing glycans. The approach thus provides a general and effective way to manipulate glycan‐protein recognition for glycoscience applications.

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The Role of Glycosylation in Inflammatory Diseases

Cited by 7 publications

References 158 publications

A Scoping Review of the Positive and Negative Bacteria Associated With the Gut Microbiomes of Systemic Lupus Erythematosus Patients

A Scoping Review of the Positive and Negative Bacteria Associated With the Gut Microbiomes of Systemic Lupus Erythematosus Patients

Human gut metagenomes encode diverse GH156 sialidases

A Computational and Chemical Design Strategy for Manipulating Glycan‐Protein Recognition

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