A Versatile Intestine‐on‐Chip System for Deciphering the Immunopathogenesis of Inflammatory Bowel Disease

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(7)

Published: Jan. 23, 2024

Abstract The multifactorial nature of inflammatory bowel disease (IBD) necessitates reliable and practical experimental models to elucidate its etiology pathogenesis. To model the intestinal microenvironment at onset IBD in vitro, it is important incorporate relevant cellular noncellular components before inducing stepwise pathogenic developments. A novel intestine‐on‐chip system for investigating multiple aspects IBD's immunopathogenesis presented. includes an array tight polarized barrier formed from epithelial cells on in‐vivo‐like subepithelial matrix within one week. dynamic remodeling by or their secretome demonstrates physiological relevance on‐chip models. design enables introduction various immune cell types stimuli specific locations same model, which facilitates investigations distinct roles each type inflammation development. It showed that behavior manifests upregulated expression markers cytokines (TNF‐α). neutralizing effect anti‐inflammatory antibody Infliximab levels TNF‐α inducible could be explicitly shown. Overall, innovative approach systematically developing a microphysiological comprehend immune‐system‐mediated disorders identify new therapeutic strategies

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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Psoriasis: Interplay between dysbiosis and host immune system

Autoimmunity Reviews, Journal Year: 2022, Volume and Issue: 21(11), P. 103169 - 103169

Published: Aug. 12, 2022

Language: Английский

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Homeostasis and Dysbiosis of the Intestinal Microbiota: Comparing Hallmarks of a Healthy State with Changes in Inflammatory Bowel Disease

Microorganisms, Journal Year: 2022, Volume and Issue: 10(12), P. 2405 - 2405

Published: Dec. 5, 2022

The gut microbiota, which represent a community of different microorganisms in the human intestinal tract, are crucial to preserving health by participating various physiological functions and acting as metabolic organ. In conditions, microbiota-host partnership exerts homeostatic stability; however, changes microbiota composition (dysbiosis) an important factor pathogenesis inflammatory bowel disease its two main entities: ulcerative colitis Crohn's disease. incidence prevalence these conditions have increased rapidly last decade, becoming significant problem for healthcare system true challenge finding novel therapeutic solutions. issue is that, despite numerous studies, etiopathogenesis not completely clear. Based on current knowledge, chronic inflammation occurs due altered environmental factors, well complex interplay between genetic predisposition host inappropriate innate acquired immune response. It note that development biological immunomodulatory therapy has led progress treating Certain lifestyle approaches-including fecal transplantation nutritional supplementation with probiotics, prebiotics, synbiotics-have offered solutions dysbiosis management paved way towards restoring healthy microbiome, only minimal long-term unfavorable effects.

Language: Английский

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Melatonin–Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions

Antioxidants, Journal Year: 2022, Volume and Issue: 11(11), P. 2244 - 2244

Published: Nov. 14, 2022

Melatonin is a pineal indolamine, allegedly known as circadian rhythm regulator, and an antioxidative immunomodulatory molecule. In both experimental clinical trials, melatonin has been shown to have positive effects in various pathologies, modulator of important biochemical pathways including inflammation, oxidative stress, cell injury, apoptosis, energy metabolism. The gut represents one melatonin's most abundant extra sources, with 400-times-higher concentration than the gland. importance microbial community-namely, microbiota, multiple critical functions organism- extensively studied throughout time, its imbalance associated variety human pathologies. Recent studies highlight possible microbiota-modulating role melatonin, implications for treatment these Consequently, might prove be valuable versatile therapeutic agent, it well elicit on microbiota many dysbiosis-associated conditions, such inflammatory bowel disease, chronodisruption-induced dysbiosis, obesity, neuropsychiatric disorders. This review intends lay basis deeper comprehension host-health subtle interactions.

Language: Английский

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Probiotic-Based Intervention in the Treatment of Ulcerative Colitis: Conventional and New Approaches

Biomedicines, Journal Year: 2022, Volume and Issue: 10(9), P. 2236 - 2236

Published: Sept. 9, 2022

Although there are number of available therapies for ulcerative colitis (UC), many patients unresponsive to these treatments or experience secondary failure during treatment. Thus, the development new alternative strategies with minimal side effects is inevitable. Strategies targeting dysbiosis gut microbiota have been tested in management UC due unquestionable role etiology UC. Advanced molecular analyses microbiomes revealed evident patients, characterized by a reduced biodiversity commensal microbiota. Administration conventional probiotic strains commonly applied approach disease modify microbiome, improve intestinal barrier integrity and function, maintain balanced immune response. However, probiotics do not always provide expected health benefits patient. Their vary significantly, depending on type stage strain dose administered. mechanism action also strain-dependent. Recently, candidates potential next-generation discovered. This could bring light approaches restoration microbiome homeostasis treatment targeted manner. The aim this paper an updated review current options probiotic-based therapies, highlight effective strains, outline future possibilities postbiotic supplementation fecal transplantation

Language: Английский

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Fusobacterium nucleatum aggravates ulcerative colitis through promoting gut microbiota dysbiosis and dysmetabolism

Journal of Periodontology, Journal Year: 2022, Volume and Issue: 94(3), P. 405 - 418

Published: Sept. 11, 2022

The correlation between periodontitis and ulcerative colitis (UC) has drawn widespread attention recently. Fusobacterium nucleatum (F. nucleatum) as a periodontal pathogen also reservoirs in gut may play role intestinal diseases. However, its the pathogenesis of UC is unclear.Mice were orally given dextran sulphate sodium (DSS) solution F. to construct experimental models. survival rate, weight, disease activity index (DAI) mice monitored. Alveolar bone loss, abundance colon, colon length, histopathological assessment, inflammatory cytokines detected. Apoptosis epithelial cells (IECs) evaluated by TUNEL assay pro-apoptotic gene Bax. barrier function was assessed tight junction proteins. By 16S rRNA sequencing LC-MS-based methods, composition microbiota metabolites analyzed.F. facilitated alveolar loss colonized only infected tissue. Mice fed with DSS showed destruction structure, increased expressions interleukin one-beta (IL-1β) tumor necrosis factor alpha (TNF-α), decreased expression IL-10, higher apoptosis IECs, dysbiosis bile acid dysmetabolism compared healthy ones. further aggravated inflammation damage. Probiotics such Bifidobacterium Faecalibacterium decreased, opportunistic pathogens Escherichia-Shigella differential microorganisms highly associated parameters metabolites. Meanwhile, level uric involving purine metabolism significantly elevated mice.F. promotes inflammation, dysfunction, aggravate UC.

Language: Английский

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Advancements in hydrogel-based drug delivery systems for the treatment of inflammatory bowel disease: a review

Biomaterials Science, Journal Year: 2023, Volume and Issue: 12(4), P. 837 - 862

Published: Dec. 22, 2023

Inflammatory bowel disease (IBD) is a chronic disorder that affects millions of individuals worldwide. However, current drug therapies for IBD are plagued by significant side effects, low efficacy, and poor patient compliance. Consequently, there an urgent need novel therapeutic approaches to alleviate IBD. Hydrogels, three-dimensional networks hydrophilic polymers with the ability swell retain water, have emerged as promising materials delivery in treatment due their biocompatibility, tunability, responsiveness various stimuli. In this review, we summarize recent advancements hydrogel-based systems We first identify three pathophysiological alterations be addressed IBD: damage intestinal mucosal barrier, dysbiosis flora, activation inflammatory signaling pathways leading disequilibrium within intestines. Subsequently, discuss depth processes required prepare hydrogel systems, from selection materials, types drugs loaded, methods loading release mechanisms key points preparation systems. Additionally, highlight progress impact system through regulation physical barrier immune responses, promotion repair, improvement gut microbiota. conclusion, analyze challenges clinical applications treatment, propose potential solutions our perspective.

Language: Английский

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Biodegradable Polymeric Nanoparticles Loaded with Flavonoids: A Promising Therapy for Inflammatory Bowel Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4454 - 4454

Published: Feb. 23, 2023

Inflammatory bowel disease (IBD) is a group of disorders that cause chronic non-specific inflammation in the gastrointestinal (GI) tract, primarily affecting ileum and colon. The incidence IBD has risen sharply recent years. Despite continuous research efforts over past decades, aetiology still not fully understood only limited number drugs are available for its treatment. Flavonoids, ubiquitous class natural chemicals found plants, have been widely used prevention treatment IBD. However, their therapeutic efficacy unsatisfactory due to poor solubility, instability, rapid metabolism, systemic elimination. With development nanomedicine, nanocarriers can efficiently encapsulate various flavonoids subsequently form nanoparticles (NPs), which greatly improves stability bioavailability flavonoids. Recently, progress also made methodology biodegradable polymers be fabricate NPs. As result, NPs significantly enhance preventive or effects on In this review, we aim evaluate effect flavonoid Furthermore, discuss possible challenges future perspectives.

Language: Английский

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Inflammatory Bowel Disease: Crosstalk between Histamine, Immunity, and Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 9937 - 9937

Published: June 9, 2023

Inflammatory bowel disease (IBD) is increasingly recognized as a serious, worldwide public health concern. It generally acknowledged that variety of factors play role in the pathogenesis this group chronic inflammatory diseases. The diversity molecular actors involved IBD does not allow us to fully assess causal relationships existing such interactions. Given high immunomodulatory activity histamine and complex immune-mediated nature disease, its receptors gut may be significant. This paper has been prepared provide schematic most important possible signaling pathways related their relevance for development therapeutic approaches.

Language: Английский

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