Single-cell omics in inflammatory bowel disease: recent insights and future clinical applications

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 334165

Published: Feb. 4, 2025

Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD), are chronic conditions characterised by inflammation of the intestinal tract. Alterations in virtually all cell types, including immune, epithelial stromal cells, have been described these diseases. The study IBD has historically relied on bulk transcriptomics, but this method averages signals across diverse limiting insights. Single-cell omic technologies overcome intrinsic limitations analysis reveal complexity multicellular tissues at a cell-by-cell resolution. Within healthy inflamed tissues, single-cell omics, particularly RNA sequencing, contributed to uncovering novel types functions linked activity or development complications. Collectively, results help identify therapeutic targets difficult-to-treat complications such as fibrostenosis, creeping fat accumulation, perianal fistulae pouch. More recently, omics gradually adopted studies understand responses, mechanisms drug failure potentially develop predictors with clinical utility. Although early days, lay groundwork for implementation practice new diagnostics, monitoring prediction prognosis. With review, we aim provide comprehensive survey that applied UC CD, offer our perspective main findings contribute. Finally, discuss potential benefits integration into could offer.

Language: Английский

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The intestinal barrier: a pivotal role in health, inflammation, and cancer

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

SummaryThe intestinal barrier serves as a boundary between the mucosal immune system in lamina propria and external environment of lumen, which contains diverse array microorganisms ingested environmental factors, including pathogens, food antigens, toxins, other foreign substances. This has central role regulating controlled interaction luminal factors system. Disruptions epithelial cells, serve physical barrier, or antimicrobial peptides mucins they produce, act chemical can lead to leaky gut. In this state, wall is unable efficiently separate flora contents from The subsequent activation an important pathogenesis inflammatory bowel disease, well metabolic dysfunction-associated steatohepatitis, primary sclerosing cholangitis, colorectal cancer. Dysregulated integrity also been described patients with chronic diseases outside gastrointestinal tract, rheumatoid arthritis neurodegenerative disorders. Mechanistic studies dysfunction have revealed that local systemic circulation activated cells cytokines secrete, extracellular vesicles, promote proinflammatory processes within tract. Review, we summarise these findings highlight several new therapeutic concepts currently being developed attempt control via direct indirect modulation function.

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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Enzymatic Oxidants, Antioxidants, and Inflammatory Bowel Disease

Applied Biosciences, Journal Year: 2025, Volume and Issue: 4(2), P. 19 - 19

Published: April 1, 2025

The role of oxidants and antioxidants in inflammatory bowel disease (IBD) has been actively explored since the early 1980s, starting with respiratory burst neutrophils ischemia pathology. Since that time, enzymatic components contributing to pool reactive oxygen species, including superoxide, H2O2, lipid hydroperoxides, counteracting antioxidants—catalase, glutathione peroxidases (Gpx), peroxiredoxins (PRDX), superoxide dismutases, others—have fleshed out. My perspective on IBD is from balance or imbalance oxidant sources process. I will present evidence involvement antioxidant processes based, as much possible, my experiences Gpxs. This be discussed terms both immune system local systems. As Gpxs are generally selenium-dependent, possible deficiencies selenium uptake active impact Gpx expression explored. more recently introduced ferroptosis, an iron-dependent peroxidation-based pathological process, reviewed for its IBD.

Language: Английский

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Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 21, 2025

Total proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas pouches using scRNA-seq scATAC-seq data from paired biopsy samples segment above (pre-pouch) (male=4, female=2), biopsies terminal ileum ascending colon healthy individuals (male=3, female=3) serving as reference. Our study finds an additional population absorptive secretory epithelial cells within but not pre-pouch. These pouch-specific enterocytes express subset colon-specific genes, including CEACAM5 CD24. However, compared to normal colonocytes, expression these genes lower, also inflammatory while maintaining some ileal-specific genes. This transcriptomic establishes reference investigating physiology pathology. Patients refractory colitis often undergo forming pouch. Here authors use single-cell genomics approach show that feature unique type which colonocyte-specific retaining marker

Language: Английский

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Deep Sequencing of Crohn’s Disease Lamina Propria Phagocytes Identifies Pathobionts and Correlates With Pro-Inflammatory Gene Expression

Inflammatory Bowel Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Crohn's disease (CD) is characterized by an inflammatory response to gut microbiota. Macrophages and dendritic cells play active role in CD inflammation. Specific microbiota have been implicated the pathogenesis of ileal CD. We investigated phagocyte-associated microbiome using unbiased sequencing approach identify potential pathobionts elucidate host these microbes. collected colonic mucosal biopsies from patients controls without bowel (IBD), isolated lamina propria phagocytes (CD11b+ cells), performed deep RNA (n = 37). Reads were mapped human genome for gene expression analysis a prokaryotic database taxonomic metatranscriptomic profiling. Results confirmed second IBD cohort 17). Lysed plated bacterial culturing; colonies underwent whole 11). contained higher relative abundances Escherichia coli, Ruminococcus gnavus, Enterocloster spp. than those controls. microbes had increased lipopolysaccharide (LPS) biosynthesis pathways. Phagocytes with pathobiont burden showed pro-inflammatory antimicrobial genes, including PI3 (antimicrobial peptide) BPIFB1 (LPS-binding molecule). E. coli more flagellar motility antibiotic resistance genes control-derived strains. Lamina resident harbor strains that may act as Our findings shed light on immune suggest new targets therapies.

Language: Английский

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Microbial-Derived Antioxidants in Intestinal Inflammation: A Systematic Review of Their Therapeutic Potential

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 321 - 321

Published: March 6, 2025

The potential of microbial-derived antioxidants to modulate intestinal inflammation is increasingly recognized, which especially important in inflammatory bowel diseases (IBD). Oxidative stress, a major contributor chronic inflammation, the result an imbalance between production reactive oxygen species (ROS) and body's antioxidant defenses. This systematic review explores role alleviating IBD. Among main findings are certain compounds, such as exopolysaccharides (EPS) short-chain fatty acids (SCFAs), have demonstrated their ability neutralize ROS strengthen integrity barrier, thereby attenuating responses. These offer dual benefit mitigating oxidative stress rebalancing gut microbiota, often disrupted Evidence from preclinical clinical studies provides better understanding mechanisms involved effects these microbial antioxidants. Conventional treatments for IBD primarily focus on immune modulation. In this context, integration could complementary approach by addressing both damage dysbiosis. Further research trials essential establish standardized treatment guidelines clarify long-term efficacy promising therapeutic agents.

Language: Английский

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Regulation of signaling pathways by metal and metal-doped nanozymes in inflammatory bowel disease: A therapeutic perspective

Nano Today, Journal Year: 2025, Volume and Issue: 63, P. 102747 - 102747

Published: April 7, 2025

Language: Английский

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A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

ABSTRACT Inflammatory bowel disease (IBD) is a chronic condition caused by altered cytokine signaling, maladaptive immunity, dysbiosis, and intestinal barrier dysfunction. Patients with IBD receive therapy to correct these imbalances achieve remission. However, most patients relapse, suggesting that pathological mechanisms persist during Here, we show excess epithelial cell death an underlying feature of arises in remission on advanced therapy. Mechanistically, nascent inflammation reprograms cells into macrophage-like state promotes RIPK1-independent necroptotic then triggers iNOS-mediated mitochondrial apoptosis absorptive PUMA-mediated stem death. These findings reveal aberrant signaling as hallmark occurs early mucosal lesion development persists despite current therapeutic approaches. One-Sentence Summary Epithelial dysregulated inflammatory disease.

Language: Английский

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Extracellular Vesicles Derived from Lipopolysaccharide-Pretreated Periodontal Ligament Stem Cells Ameliorate Inflammatory Responses in Experimental Colitis via the PI3K/AKT Signaling Pathway

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 11997 - 12013

Published: Nov. 1, 2024

Inflammatory bowel disease is a complex chronic inflammatory condition characterized by dysbiosis of the gut microbiota and dysregulation immune system. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells have garnered significant attention for their beneficial potentials in modulation tissue repair. This study aims to evaluate therapeutic effects underlying mechanisms EVs lipopolysaccharide (LPS)-pretreated periodontal ligament (PDLSCs) mice with colitis.

Language: Английский

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