New insights into the intestinal barrier through “gut-organ” axes and a glimpse of the microgravity’s effects on intestinal barrier

Frontiers in Physiology, Год журнала: 2024, Номер 15

Опубликована: Окт. 10, 2024

Gut serves as the largest interface between humans and environment, playing a crucial role in nutrient absorption protection against harmful substances. The intestinal barrier acts initial defense mechanism non-specific infections, with its integrity directly impacting homeostasis health of human body. primary factor attributed to impairment previous studies has always centered on gastrointestinal tract itself. In recent years, concept "gut-organ" axis gained significant popularity, revealing profound interconnection gut other organs. It speculates that disruption these axes plays pathogenesis progression damage. evaluation function detection enterogenic endotoxins can serve "detecting agents" for identifying early functional alterations heart, kidney, liver, thereby facilitating timely intervention disorders. Simultaneously, consolidating may also present potential therapeutic approach attenuate damage Studies have demonstrated diverse signaling pathways their corresponding key molecules are extensively involved pathophysiological regulation barrier. Aberrant activation dysregulated expression play pivotal process impairment. Microgravity, being predominant characteristic space, potentially exert influence barriers. We will discuss interaction damage, further elucidate underlying summarize various components under microgravity. This review aims offer novel perspective comprehending etiology molecular mechanisms injury well prevention management microgravity environment.

Язык: Английский

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Allergic rhinitis in children is associated with high serum levels of zonulin

International Journal of Pediatric Otorhinolaryngology, Год журнала: 2025, Номер unknown, С. 112350 - 112350

Опубликована: Апрель 1, 2025

Язык: Английский

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Effects of POPs-induced SIRT6 alteration on intestinal mucosal barrier function: A comprehensive review

Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 289, С. 117705 - 117705

Опубликована: Янв. 1, 2025

Persistent organic pollutants (POPs) are pervasive chemicals with significant environmental and ecological ramifications, extending to adverse human health effects due their toxicity persistence. The intestinal mucosal barrier, a sophisticated defense mechanism comprising the epithelial layer, chemistry, cellular immunity, shields host from external threats fosters symbiotic relationship bacteria. Sirtuin 6 (SIRT6), sirtuin family member, is pivotal in genome telomere stability, inflammation regulation, metabolic processes. Result shows POPs have been implicated diseases, particularly barrier dysfunction, through mechanisms such as damage, epigenetic alterations, inflammation, microbiota changes, disruptions. While impact of SIRT6 expression changes on functions has reviewed, linking remain elusive. This review summarized latest research results discussed role multiple perspectives, proposed new directions POPs, health, explored therapeutic potential SIRT6.

Язык: Английский

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Novel Transcriptomic Signatures in Fibrostenotic Crohn’s Disease: Dysregulated Pathways, Promising Biomarkers, and Putative Therapeutic Targets

Inflammatory Bowel Diseases, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Fibrosis is a common complication in Crohn's disease (CD), often leading to intestinal strictures. This study aims explore the transcriptomic signature of fibrostenotic ileal CD for comprehensive characterization biological and cellular mechanisms underlying fibrosis. Nine patients undergoing surgery fibrotic strictures were prospectively recruited. RNA was extracted from fresh resected samples bulk transcriptomics. Differentially expressed genes (DEGs) identified (adj. P value < .05), machine learning analyses employed compare gene expression patterns between non-strictured margins. Pathway enrichment analysis pinpointed relevant pathways. Furthermore, random forest model constructed evaluate significance targeted genes. Relevant subsequently validated through qPCR further analyzed using publicly available RNA-seq dataset (GSE192786). Single-cell sequencing (scRNA-seq) performed 10× Chromium Controller platform. Bulk transcriptomics revealed unique transcriptomes with 81 DEGs, 64 significantly up-regulated, 17 down-regulated compared Up-regulated mainly associated inflammation, matrix tissue remodeling, adipogenesis stress, while linked epithelial barrier integrity. LY96, AKAP11, SRM, GREM1, EHD2, SERPINE1, HDAC1, FGF2 showed high specificity scRNA-seq up-regulated GREM1 exclusively fibroblasts, EHD2 upregulation both fibroblasts endothelial cells. LY96 SRM by immune cells, whereas SERPINE1 low across all subsets. comprehensively characterizes strictures, elucidating main dysregulated pathways identifying promising biomarkers putative therapeutic targets.

Язык: Английский

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Interplay of gut microbiota in Kawasaki disease: role of gut microbiota and potential treatment strategies

Future Microbiology, Год журнала: 2025, Номер unknown, С. 1 - 13

Опубликована: Фев. 27, 2025

Kawasaki disease (KD) is an acute systemic immune vasculitis with predominant involvement of the medium and small arteries. It mostly affects pediatric patients, representing most common form in children less than 5 years old. Numerous diseases, especially those related to system, have established links intestinal flora. Recent studies investigated flora changes throughout management KD. There was gut microbiota dysbiosis KD at phase, particularly downregulation short-chain fat acids-producing over-proliferation opportunistic pathogens. The relationship between response therapies individuals specific remains uncertain. Targeted microbial supplements dietary regulation may serve as potential measures alleviate complications thus improve prognosis. This review provides overview current understanding interplay Furthermore, it discusses possibility altering reinstate a healthy condition.

Язык: Английский

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AI-enabled ‘endo-histo-omics’: breaking down intestinal barriers in IBD

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Язык: Английский

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The Ulcerative Colitis-Associated Gene NXPE1 Catalyzes Glycan Modifications on Colonic Mucin

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Colonic mucus forms a first line of defense against bacterial invasion while providing nutrition to support coinhabiting microbes in the gut. Mucus is composed polymeric networks mucin proteins, which are heavily modified post-translationally. The full compendium enzymes responsible for these modifications and their roles health disease remain incompletely understood. Herein, we determine biochemical function NXPE1, gene implicated ulcerative colitis (UC), demonstrate that it encodes an acetyltransferase modifies glycans. Specifically, NXPE1 utilizes acetyl-CoA regioselectively modify sialic acid, 5-N-acetylneuraminic acid (Neu5Ac), at 9-OH group generate 9-O-acetylated Neu5Ac (Neu5,9Ac2). We further colonic organoids derived from donors harboring missense variant G353R, protective UC, exhibit severely impaired acetylation on mucins. Together, our findings model masks alcohols sialoglycans via acetylation, important modulating barrier properties limit interactions with commensal microbes.

Язык: Английский

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Therapeutic potential of gut microbiota modulation in epilepsy: A focus on short-chain fatty acids

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106880 - 106880

Опубликована: Март 1, 2025

According to the criteria established by International League Against Epilepsy (ILAE), epilepsy is defined as a disorder characterized at least two unprovoked seizures occurring more than 24 h apart. Its pathogenesis closely related various physiological and pathological factors. Advances in high-throughput metagenomic sequencing have increasingly highlighted role of gut microbiota dysbiosis epilepsy. Short-chain fatty acids (SCFAs), major metabolites key regulators gut-brain axis, support homeostasis through multiple mechanisms. Recent studies indicated that SCFAs not only regulate maintaining intestinal barrier integrity modulating immune responses, but also affect structure function blood-brain (BBB) neuroinflammation. This review, based on current literatures, explores relationship between epilepsy, emphasizing how BBB. In-depth may reveal their therapeutic potential inform development microbiota-targeted treatments.

Язык: Английский

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Si-Ni Decoction as a Potential Treatment for Ulcerative Colitis: Modulation of Gut Microbiota and AKT1 Inhibition Through Network Pharmacology and in vivo Validation

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 6263 - 6280

Опубликована: Май 1, 2025

Sini Decoction (SND), a time-honored formulation in traditional Chinese medicine, consists of three key ingredients: aconite, licorice, and ginger rhizome. It has been used for more than thousand years to relieve symptoms associated with acute gastroenteritis, dyspepsia, abdominal discomfort, but its therapeutic efficacy ulcerative colitis (UC) the mechanisms involved have not validated. In this study, comprehensive approach integrating network pharmacology, molecular docking, dynamics simulation experimentation was assess SND treatment UC explore mechanisms. The bioactive compounds were identified using TCMSP database, potential targets predicted via Swiss Target Prediction database. Protein-protein interaction networks constructed STRING database Cytoscape most important genes identified. Subsequently, docking combined simulations binding affinity main active ingredient AKT1. To evaluate effects SND, we utilized dextran sodium sulfate-induced mouse model. Additionally, fecal samples collected analysis intestinal microbiota influence on gut flora composition. Fifteen components from identified, their activities results indicated that AKT serine/threonine kinase 1 is core target UC. anti-inflammatory, barrier-protective, microbiota-regulating confirmed animal models, alongside evidence inhibitory effect ingredients screened, focus AKT1 inhibition, reduce inflammation UC, protect barrier, regulate microbiota, demonstrating significant potential.

Язык: Английский

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Latest Advanced Techniques for Improving Intestinal Organoids Limitations

Stem Cell Reviews and Reports, Год журнала: 2025, Номер unknown

Опубликована: Май 19, 2025

Язык: Английский

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