Biochemical and structural basis of sialic acid utilization by gut microbes

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(3), P. 102989 - 102989

Published: Feb. 8, 2023

The human gastrointestinal (GI) tract harbors diverse microbial communities collectively known as the gut microbiota that exert a profound impact on health and disease. repartition availability of sialic acid derivatives in have significant modulation microbes host susceptibility to infection inflammation. Although N-acetylneuraminic (Neu5Ac) is main form acids humans, family regroups more than 50 structurally chemically distinct modified derivatives. In GI tract, are found terminal location mucin glycan chains constituting mucus layer also come from milk oligosaccharides infant or meat-based foods adults. influences composition pathogen colonization. this review, we provide an update mechanisms underpinning utilization by microbes, focusing sialidases, transporters, metabolic enzymes. Correction: Biochemical structural basis microbesJournal Biological ChemistryVol. 299Issue 4PreviewIn JBC Reviews article entitled "Biochemical microbes" arrows Figure 6 should be adjusted. correct provided below. Full-Text PDF Open Access

Language: Английский

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Coprophagy Prevention Affects the Reproductive Performance in New Zealand White Rabbits Is Mediated through Nox4-ROS-NFκB Pathway

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 13

Published: Dec. 21, 2022

Coprophagy is of great significance to the growth, development, and reproductive performance rabbits. This study aimed at exploring effect coprophagy on New Zealand white rabbits by prevention (CP). The results showed that CP treatment significantly decreased growth development female live birth rate embryos. blood biochemical indexes increased contents serum ALB, ALP, MDA, while SOD activity was decreased. Transcriptome analysis GO terms were mainly enriched in transport function after treatment. In addition, KEGG inflammation related signal pathways activated expression level genes tight junction proteins downregulated Concurrently, western blot further confirmed KEGG. short, fecal feeding an important survival strategy for some small rodents, will affect inflammatory body, change oxidative stress then activate NOX4-ROS-NF-κB pathway, increase adhesion protein ICAM-1 VCAM-1, lead damage uterine epithelial barrier,

Language: Английский

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Mucin networks: Dynamic structural assemblies controlling mucus function

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 79, P. 102524 - 102524

Published: Feb. 6, 2023

Contrary to first appearances, mucus structural biology is not an oxymoron. Though hydrogels derive their characteristics largely from intrinsically disordered, heavily glycosylated polypeptide segments, the secreted mucin glycoproteins that constitute undergo orderly assembly process controlled by folded domains at termini. Recent studies revealed how complexes promote disulphide-mediated polymerization produce gel scaffold. Additional protein–protein and protein-glycan interactions likely tune mesoscale properties, stability, activities of mucins. Evidence emerging even disordered segments have specific roles in production properties mucus. soft-matter biophysical approaches understanding remain highly relevant, high-resolution mucins other components are providing new perspectives on these vital, protective hydrogels.

Language: Английский

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Effect of Extracelluar Vesicles Derived from Akkermansia muciniphila on Intestinal Barrier in Colitis Mice

Nutrients, Journal Year: 2023, Volume and Issue: 15(22), P. 4722 - 4722

Published: Nov. 8, 2023

Inflammatory bowel disease (IBD) is a chronic and recurrent disease. It has been observed that the incidence prevalence of IBD are increasing, which consequently raises risk developing colon cancer. Recently, regulation intestinal barrier by probiotics become an effective treatment for colitis. Akkermansia muciniphila-derived extracellular vesicles (Akk EVs) nano-vesicles contain multiple bioactive macromolecules with potential to modulate barrier. In this study, we used ultrafiltration in conjunction high-speed centrifugation extract Akk EVs. A lipopolysaccharide (LPS)-induced RAW264.7 cell model was established assess anti-inflammatory effects found EVs were able be absorbed cells significantly reduce expression nitric oxide (NO), TNF-α, IL-1β (p < 0.05). We explored preventative on colitis regulating using mouse caused dextran sulfate sodium (DSS). The findings demonstrated effectively prevented symptoms reduced colonic tissue injury. Additionally, enhanced effectiveness elevating MUC2 (0.53 ± 0.07), improving mucus integrity, reducing permeability Moreover, increased proportion beneficial bacteria Firmicutes (33.01 0.09%) downregulated harmful Proteobacteria (0.32 0.27%). These suggest possess ability regulate immune responses, protect barriers, gut microbiota. research presents intervention approach prevent

Language: Английский

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Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 4, 2023

Abstract Mucin-domain glycoproteins are densely O-glycosylated and play critical roles in a host of biological functions. In particular, the T cell immunoglobulin mucin-domain containing family proteins (TIM-1, -3, -4) decorate immune cells act as key regulators cellular immunity. However, their dense O-glycosylation remains enigmatic, primarily due to challenges associated with studying mucin domains. Here, we demonstrate that mucinase SmE has unique ability cleave at residues bearing very complex glycans. enables improved mass spectrometric analysis several mucins, including entire TIM family. With this information in-hand, perform molecular dynamics (MD) simulations TIM-3 -4 understand how glycosylation affects structural features these proteins. Finally, use models investigate functional relevance for function ligand binding. Overall, present powerful workflow better detailed structures functions mucinome.

Language: Английский

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Bacteroides methylmalonyl-CoA mutase produces propionate that promotes intestinal goblet cell differentiation and homeostasis

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 32(1), P. 63 - 78.e7

Published: Dec. 5, 2023

Language: Английский

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DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 9, 2024

Abstract Epithelial barrier dysfunction and crypt destruction are hallmarks of inflammatory bowel disease (IBD). Intestinal stem cells (ISCs) residing in the crypts play a crucial role continuous self-renewal rapid recovery intestinal epithelial (IECs). However, how ISCs dysregulated IBD remains poorly understood. Here, we observe reduced DHX9 protein levels patients, mice with conditional depletion epithelium ( Dhx9 ΔIEC ) exhibit an increased susceptibility to experimental colitis. Notably, display significant reduction numbers Paneth cells. Further investigation using ISC-specific or cell-specific -deficient demonstrates involvement ISC-expressed maintaining homeostasis. Mechanistically, deficiency leads abnormal R-loop accumulation, resulting genomic instability cGAS-STING-mediated response, which together impair ISC function contribute pathogenesis IBD. Collectively, our findings highlight R-loop-mediated as risk factor

Language: Английский

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Gut microbiota and blood biomarkers in IBD-Related arthritis: insights from mendelian randomization

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

With the ongoing rise in incidence of inflammatory bowel disease (IBD), its extraintestinal manifestations have garnered significant attention. IBD-related arthritis is notable for insidious onset and unpredictability, presenting considerable challenges clinical diagnosis management. Factors such as gut microbiota, plasma proteins, biomarkers found blood urine may be closely associated with arthritis. However, mechanisms by which these factors influence this condition remain poorly understood require urgent investigation. We employed method linkage disequilibrium two-sample Mendelian randomization (MR) approach, utilizing single nucleotide polymorphisms (SNPs) identified from large-scale genome-wide association studies instrumental variables. In scientifically rigorous manner, we explored potential causal relationship between relation to resulting (IBD). This aids elucidating roles development following IBD, while minimizing confounding reverse causality commonly encountered observational studies. To further verify strengthen our findings, conducted subsequent sensitivity analyses. These analyses will evaluate strength SNPs studied biomarkers, well post-IBD arthritis, accounting variations SNP distribution among populations other genetic influencing factors. Through analytical steps, objective enhance robustness credibility research findings provide more reliable scientific evidence regarding pathogenesis MR analysis provides genetically predicted risk investigates characteristics associations specific Among pterin-4-alpha-carbinolamine dehydratase, aldo-keto reductase family 1 member C4, cathepsin L2, angiostatin, hepatocyte growth factor-like protein, hepatitis A virus cellular receptor 2, protein O-linked mannose beta-1,4-N-acetylglucosaminyltransferase epididymal-specific alpha-mannosidase, platelet-derived factor receptor-like are Crohn's disease-related contrast, agrin, methylenetetrahydrofolate synthetase domain-containing neurotrophin-3 (NT-3) receptor, neuropilin-1 ulcerative colitis-related Furthermore, bacterial pathway abundance, adenosylcobalamin, N-acetylglucosamine, N-acetylmannosamine, N-acetylneuraminic acid degradation, glycolysis metabolism degradation pathways, Meanwhile, abundance (pentose phosphate pathway) microbiota (Bacteroidetes, Bacteroidia, Bacteroidales, Porphyromonadaceae, Faecalibacterium, Eubacterium eligens) linked Notably, did not identify any connections factors, Lastly, study, insufficient number available precluded detection a relationship. study employs elucidate relationships occurrence progression offers novel perspective deeper understanding highlights future directions treatment strategies condition.

Language: Английский

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Gut Microbiota Serves as a Crucial Independent Biomarker in Inflammatory Bowel Disease (IBD)

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2503 - 2503

Published: March 11, 2025

Inflammatory bowel disease (IBD), encompassing Crohn’s (CD), ulcerative colitis (UC), and IBD unclassified (IBD-U), is a complex intestinal disorder influenced by genetic, environmental, microbial factors. Recent evidence highlights the gut microbiota as pivotal biomarker modulator in pathogenesis. Dysbiosis, characterized reduced diversity altered composition, hallmark of IBD. A consistent decrease anti-inflammatory bacteria, such Faecalibacterium prausnitzii, an increase pro-inflammatory species, including Escherichia coli, have been observed. Metabolomic studies reveal decreased short-chain fatty acids (SCFAs) secondary bile acids, critical for homeostasis, alongside elevated metabolites. The interacts with host immune pathways, influencing morphogens, glycosylation, podoplanin (PDPN) expression. disruption glycosylation impairs mucosal barriers, while aberrant PDPN activity exacerbates inflammation. Additionally, alterations contribute to oxidative stress, further destabilizing barriers. These molecular cellular disruptions underscore role microbiome pathophysiology. Emerging therapeutic strategies, probiotics, prebiotics, dietary interventions, aim restore balance mitigate Advanced on microbiota-targeted therapies their potential reduce severity improve patient outcomes. Nevertheless, research needed elucidate bidirectional interactions between responses translate these insights into clinical applications. This review consolidates current findings microbiota’s IBD, emphasizing its diagnostic implications, advocates continued exploration microbiome-based interventions combat this debilitating disease.

Language: Английский

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Role of the mucin-like glycoprotein FCGBP in mucosal immunity and cancer

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 22, 2022

IgGFc-binding protein (FCGBP) is a mucin first detected in the intestinal epithelium. It plays an important role innate mucosal epithelial defense, tumor metastasis, and immunity. FCGBP forms disulfide-linked heterodimers with mucin-2 members of trefoil factor family. These formed complexes inhibit bacterial attachment to surfaces, affect motility pathogens, support their clearance. Altered expression levels may be pathologic processes Crohn’s disease ulcerative colitis. also involved regulating infiltration immune cells into microenvironments. Thus, molecule valuable marker prognosis. This review summarizes functional relevance responses development, highlights potential diagnosis predicting

Language: Английский

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