Integrating multi-omics to unravel host-microbiome interactions in inflammatory bowel disease

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(9), P. 101738 - 101738

Published: Sept. 1, 2024

Language: Английский

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Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2789 - 2789

Published: Feb. 28, 2024

The advent of biologic drugs has revolutionized the treatment Inflammatory Bowel Disease, increasing rates response and mucosal healing in comparison to conventional therapies by allowing corticosteroid-refractory cases reducing corticosteroid-related side effects. However, (anti-TNFα inhibitors, anti-α4β7 integrin anti-IL12/23) are still burdened that hover around 40% (in biologic-naïve patients) or lower (for biologic-experienced patients). Moreover, knowledge mechanisms underlying drug resistance loss is scarce. Several cellular molecular determinants implied therapeutic failure; genetic predispositions, form single nucleotide polymorphisms sequence cytokines Human Leukocyte Antigen, an altered expression other molecules involved inflammation cascade, play most important role. Accessory include gut microbiota dysregulation. In this narrative review current recent literature, we shed light on mentioned failure order pave way for a more personalized approach could help avoid unnecessary treatments toxicities.

Language: Английский

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Inflammatory bowel disease genomics, transcriptomics, proteomics and metagenomics meet artificial intelligence

United European Gastroenterology Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 31, 2024

Abstract Various extrinsic and intrinsic factors such as drug exposures, antibiotic treatments, smoking, lifestyle, genetics, immune responses, the gut microbiome characterize ulcerative colitis Crohn's disease, collectively called inflammatory bowel disease (IBD). All these contribute to complexity heterogeneity of etiology pathogenesis leading major challenges for scientific community in improving management, medical genetic risk, exposome impact. Understanding interaction(s) among their effects on system IBD patients has prompted advances multi‐omics research, development new tools part biology, more recently, artificial intelligence (AI) approaches. These innovative approaches, supported by availability big data large volumes digital datasets, hold promise better understanding natural histories, predictors development, severity, complications treatment outcomes complex diseases, providing decision support doctors, promising bring us closer realization “precision medicine” paradigm. This review aims provide an overview current omics based both individual (genomics, transcriptomics, proteomics, metagenomics) levels, highlighting how AI can facilitate integration heterogeneous summarize our identify gaps knowledge inform upcoming research this field.

Language: Английский

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Laboratory Tests in Inflammatory Bowel Disease: An Evidence-Based Approach to Daily Practice

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 491 - 491

Published: Feb. 17, 2025

Inflammatory bowel diseases (IBDs) comprise a group of chronic gastrointestinal disorders characterized by periods relapse and remission. The mainstay treatment is medical, involving medications such as steroids, immune modulators, monoclonal antibodies (categorized biologics), small molecules. These can provide profound therapeutic benefits, but they also cause severe irreversible toxicities. Clinicians may utilize laboratory tests in the diagnosis management IBD including assessment disease activity, monitoring medication response or toxicity, surveillance infectious complications, detection nutritional deficiencies. Routine use help clinicians avoid reactivation life-threatening infections tuberculosis hepatitis B virus upon initiation suppressive therapy. They be used to detect vitamin deficiencies B12 deficiency, which has potential neurologic damage. While some constitute established practices, utility newer drug (TDM) era biologics an evolving topic. Although clinical with imaging, endoscopic, histopathological examination standard practice, serve valuable adjuncts. We aim explore broad range available summarize their application current daily special attention updates monitoring.

Language: Английский

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DAMP-ing IBD: Extinguish the Fire and Prevent Smoldering

Digestive Diseases and Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

In inflammatory bowel diseases (IBD), the most promising therapies targeting cytokines or immune cell trafficking demonstrate around 40% efficacy. As IBD is a multifactorial inflammation of intestinal tract, single-target approach unlikely to solve this problem, necessitating an alternative strategy that addresses its variability. One often overlooked by pharmaceutically driven therapeutic options address impact environmental factors. This somewhat surprising considering increasingly viewed as condition heavily influenced such factors, including diet, stress, and pollution-often referred "Western lifestyle". IBD, responses result from complex interplay among genetic background patient, molecules, cells, local microenvironment where danger- microbe-associated molecular patterns (D/MAMPs) provide adjuvant-rich environment. Through activating DAMP receptors, array pro-inflammatory factors can stimulate, for example, NLRP3 inflammasome-a major amplifier response in various cells via non-specific bystander activation myeloid (e.g., macrophages) lymphocytes tissue-resident memory T cells). Current biological treatment approaches dampen response, but without reducing exposure e.g., changing diet (reducing ultra-processed foods), landscape never resolved continues drive mucosal dysregulation. Thus, are not enough put out fire. The resultant smoldering, low-grade diminishes physiological resilience (micro)environment, perpetuating state chronic disease. Therefore, our hypothesis posits successful interventions must complexity disease simultaneously all modifiable aspects: innate immunity microbiota, adaptive cytokines, relate (micro)environment. Thus be comprehensively treated across nano-, meso-, microscales, rather than with focus on single targets. A broader perspective also includes adapt DAMPing (micro)environment warranted.

Language: Английский

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The Role of the Microbiome and of Radiotherapy-Derived Metabolites in Breast Cancer

Cancers, Journal Year: 2024, Volume and Issue: 16(21), P. 3671 - 3671

Published: Oct. 30, 2024

The gut microbiome has emerged as a crucial player in modulating cancer therapies, including radiotherapy. In the case of breast cancer, interplay between and radiotherapy-derived metabolites may enhance therapeutic outcomes minimize adverse effects. this review, we explore bidirectional relationship cancer. We explain how composition influences progression treatment response, its treatments influence composition. A dual role for is explored article, highlighting both their benefits potential hazards. By integrating genomics, metabolomics, bioinformatics tools, present comprehensive overview these interactions. study provides real-world insight through studies clinical trials, while innovations such probiotics, dietary interventions are examined to modulate effectiveness. Moreover, ethical considerations patient perspectives discussed, ensuring understanding subject. Towards revolutionizing strategies improving outcomes, review concludes with future research directions. It also envisions metabolite into personalized therapy.

Language: Английский

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Long noncoding RNAs and circular RNAs as potential diagnostic biomarkers of inflammatory bowel diseases: a systematic review and meta-analysis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 8, 2024

Introduction Inflammatory bowel disease (IBD) poses a growing global burden, necessitating the discovery of reliable biomarkers for early diagnosis. The clinical significance dysregulated expression long noncoding RNAs (lncRNAs) and circular (circRNAs) in diagnosing IBD has not been well established. Thus, our study aimed to investigate diagnostic value lncRNAs circRNAs based on currently available studies. Methods A comprehensive search was carried out diverse electronic databases, such as PubMed, Embase, Scopus, Science Direct Wiley Online Library retrieve articles published until October 30, 2023. Stata 17.0 software employed determine pooled sensitivity, specificity, positive likelihood ratio (PLR), negative (NLR), (DOR), area under curve (AUC). Heterogeneity, subgroup analysis, meta-regression were explored, publication bias assessed using Deeks’ funnel plot. Fagan’s nomogram scattergram evaluate validity. Result total 11 encompassing 21 studies which involved 1239 patients 985 healthy controls investigated. findings revealed exhibit high level sensitivity 0.94 (95% CI: 0.87-0.97) specificity 0.99 0.89-1.00), along with PLR, NLR, DOR, AUC values 64.25 7.39-558.66), 0.06 0.03-0.13), 1055.25 70.61-15770.77), 0.97-0.99), respectively. Conversely, CircRNAs showed moderate accuracy diagnosis, 0.68 0.61-0.73), 0.73 0.65-0.79), PLR 2.47 1.94-3.16), NLR 0.45 0.38-0.53), DOR 5.54 3.88-7.93), 0.75 0.71-0.79). Moreover, from analysis depicted heightened efficacy when employing lncRNA H19 large sample size (≥100), notable both ulcerative colitis (UC) Crohn’s (CD). Conclusion LncRNAs distinguishing signifying their possible use potential biomarkers, while accuracy. Nevertheless, validate confirm utility pool prospective multi-center should be undertaken. Systematic review registration https://www.crd.york.ac.uk/PROSPERO , identifier CRD42023491840.

Language: Английский

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GutUDB: A comprehensive multiomics database for intestinal diseases

iMeta, Journal Year: 2024, Volume and Issue: 3(3)

Published: April 27, 2024

Gut Universe Database (GutUDB) provides a comprehensive, systematic, and practical platform for researchers, is dedicated to the management, analysis, visualization of knowledge related intestinal diseases. Based on this database, eight major categories omics data analyses are carried out explore genotype-phenotype characteristics certain disease. The first tool comprehensive research diseases will help each researcher better understand intestine serves as central organ in digestive system nutrient absorption digestion processes [1]. In recent years, high-throughput sequencing technologies have significantly broadened our comprehension biological mechanisms from diverse aspects, including DNA-level processes, transcriptional dynamics, protein-related activities, epigenetic modifications. These various could provide more systematic insight into [2, 3]. However, complexity analytical techniques data, coupled with dispersed nature storage voluminous size sets, has impeded researchers fully exploit these resources [4, 5]. Therefore, establishment database integrate analyze sets would be urgent instrumental dealing challenges. Here, we present (GutUDB), high-quality multiomics about It user-friendly collection types epigenomics, genomics, transcriptomics, spatial omics, single-cell proteomics, metabolomics, microbiomics spanning 56 distinct across six species. GutUDB offers thorough analysis diseases, presenting through informative charts. We also highlight therapeutic targets both chemical traditional medicine suitable along associated outcomes involving probiotics. play pivotal role identifying diagnostic unveiling molecular underlying progression conditions. To date, accumulated approximately 9 million generated profiles which encompasses species: Homo sapiens, Mus musculus, Rattus norvegicus, Macaca mulatta, Danio rerio, Sus scrofa. Overall, incorporated 58,970 genes derived 11 subtypes tissue or 63 cell lines, identified potential clinical therapeutics, drugs, medicine, probiotic agents. assist users easily elucidate interrogate intricate gene-disease-omics network, four core functionalities—Browse, Query, Visualization, Download—were integrated (Figure 1A). total, 260,790 disease-gene associations were embedded GutUDB. main intestine-related colon cancer, colorectal cancer (CRC), bleeding colon, rectal constipation, diarrhea, ileus, inflammatory bowel disease, small (Supporting Information: Figure S1A), shared common such STK11, CFTR, BMPR1A, SMAD4, NOTCH1, PKD1, MLH1, MSH2, APC, MEFV S1B) [6-11]. Specifically, STK11 well-known etiological factor Peutz-Jeghers syndrome. SMAD4 BMPR1A reported Juvenile Polyposis Syndrome [12]. findings illustrated strong relationship between pathologies genes. further specific can obtain detailed information homepage using gene symbols. For example, METTL3, upon clicking "Search" icon, results exhibited details gene, genome location functional (e.g., RNA-binding protein transcription factor) S1C), expression levels patterns different tissues 1B). observed frequency copy number variation (CNV) deletion only 0.04 METTL3 CRC, while there was high RNA gene. concluded that weak correlation CNV similar conducted other proteomics S1D). Additionally, specifically offered differential survival prognosis adenocarcinoma (COAD) patients 1C–E). primarily divided modules—SPECIES, DISEASES, OMICS, THERAPY, facilitating access browse corresponding icon homepage. "THERAPY" module, curated 21,984 drug-disease interactions, 6281 compounds, 393 medicinal herbs, 22 probiotics S1E). Among associations, cisplatin, chemotherapy drug patients, infiltrate tumor cells, induce DNA damage, ultimately lead death [13]. demonstrated cisplatin had connectivity drug-disease-gene highlighting reliability accessibility stored "DISEASES" take deeper interest disorders S1F). "SPECIES" all select species they interested S1G). All presented tabular format facilitated efficiently retrieve filter them by inputting keywords symbol type disease) terms level hot genes) at top current page. Recently, methods advanced study cellular heterogeneity, immune regulation, revealed maps delineating tumor-specific samples, annotation maps. Upon selecting peruse gene-related Furthermore, provided sample, type, biotechnology, gene's showed uniform manifold approximation projection plots RNA-seq, sample's detail page contained cells 1F). Besides, expression, alternative polyadenylation, splicing, GutUDB, comprehensively regulatory dimensions proteins level. facilitate integration types, combined complex interplay among DNA, RNA, proteins, aspects genetic turbulence. Users assess "Omics" option navigation bar. Eight bulk interactive visualization. Epigenetics plays crucial development screened utilized molecules diagnosis biomarkers trials [14]. three mainly epigenomics embedded, methylation, histone modification (H3K27me3, H3K27ac, H3K36me3, H3K4me1, H3K4me3, H3K9me3), chromosome structure. them, posttranscriptional m6A focal points research. Here demonstrate status, H3K27me3 modification, MUTYH an example 1G). miCLIP-seq, 1908 sites included As alterations influence result transcript alteration, may consequently affect levels. splicing exon skipping, 5′splice site, 3′splice mutually exclusive exons, retained introns [15]. use status CRC currently includes 72,248 single-nucleotide polymorphisms (SNPs), 54,131 CNVs, 1097 structural variations (SVs), 92,888 mutated established "Statistics" Notably, genomic alternation accompanied its populations well set source. SNP 137 RNA-seq 7.9 under conditions collected S1H). noncoding RNAs separately displayed panels, 62 circular RNAs, 182 long 58 microRNAs. proteomic metabolomic profiles, aberrations impact pathophysiology [16, 17]. domains, active sites, posttranslational modifications artificial regulation. Moreover, metabolomics 2764 relationships gut microbes metabolites enabled conduct deep interconnections multiple insights, thus sophisticated study, challenge standardization integrating platforms, microarray data. Admittedly, platforms instruments. Our utilizes transcriptomics due it still standardized compared effectively. Integrating illuminate pathogenic changes enhance understanding disease diagnosis, mechanisms, treatment strategies [18]. definitely serve resource wide range users, clinicians specializing gastroenterology, academic scientific institutions, educators students universities anyone applications. get extensive array directly without exhaustive searches disease-specific databases, repositories, microbiome databases. With rapid accumulation responsible frequently updating proudly announce serving open-access global community advance plan models within next 1–2 real-time communication platform. pathological slides radiomics cohorts individuals all, procedures ensure obtains newest latest Sanqi An, Shuaiyi Liang, HaoLiang, Xuena Chen conceived designed revised manuscript, prepared publication. Yi Bao, Yaxin Chen, Lizhu Lin, Jingyi Li implementation supervision project, analyzed results, built website, interpreted wrote manuscript. Gang Wang Xinli Liu performed analysis. Yueqi Yao Lin assisted application. Yajing Lijuan Zhou organized reviewed Yawen Qi Yufang Xie excluded corrected Zhenrui Zhe Sun, Yuwen Fan, Jinjing Jiang, Feiyu Zhang part Hubin Jiemei Chu, Jiegang Huang search relevant literatures. authors read final manuscript approved like thank Wanan Daowen Yang Baidu Health Team their contributions construction website. This work supported National Natural Science Foundation China (82160389), Guangxi Medical University Training Program Distinguished Young Scholars Technology Base Talent Project (2022AC19006). declare no conflict interest. No animals humans involved study. sources Supporting Information (Table S1). freely available https://intestine.splicedb.net. code tables figures article been uploaded GitHub https://github.com/Ansanqi/GutUDB. (methods, figures, tables, scripts, graphical abstract, slides, videos, Chinese translated version, updated materials) found online DOI iMeta http://www.imeta.science/. Please note: publisher not content functionality any supporting supplied authors. Any queries (other than missing content) should directed author article.

Language: Английский

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Considerations in Paediatric and Adolescent Inflammatory Bowel Disease

Journal of Crohn s and Colitis, Journal Year: 2024, Volume and Issue: 18(Supplement_2), P. ii31 - ii45

Published: Oct. 1, 2024

Abstract The incidence of inflammatory bowel disease [IBD] is rising most rapidly among children and adolescents. Paediatric-onset IBD associated with a more extensive severe course compared to adult-onset IBD. At young age, screening for underlying genetic immunological disorders important may impact treatment management. Early effective crucial reach remission prevent complications ongoing active disease. In Crohn’s disease, exclusive enteral nutrition an induction therapy. Other promising dietary therapies, such as the exclusion diet, are emerging. Within paediatric IBD, anti-tumour necrosis factor therapy only approved biological thus far additional options crucially needed. vedolizumab ustekinumab, currently prescribed off-label in this population. A specific challenge unacceptable major delay approval drugs guided transfer period patients adult care improved outcomes required. Major knowledge gaps challenges within include aetiology, diagnostics, monitoring tailoring treatment, both understanding coping physical psychological consequences living Challenges research paediatrics should be addressed without any comparison field, order ensure high quality all irrespective age onset.

Language: Английский

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Multi-omics phenotyping characterizes molecular divergence underlying different clinical scenarios of inflammatory bowel disease

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

Published: May 15, 2024

ABSTRACT Clinically heterogeneous spectrum and molecular phenotypes of inflammatory bowel disease (IBD) remain to be comprehensively elucidated. This study set out explore the serum profiles (I) IBD subtypes; in association with (II) elevated fecal calprotectin (III) activity states; (IV) upon treatment escalation; (V) patients who needed escalation. The proteome, metabolome, lipidome 75 treated were profiled. Single- multi-omic data analysis was performed determine differential analytes integrative biosignatures. Chronic inflammation, phosphatidylcholine bile acid homeostasis disturbances underlined differences between Crohn’s (CD) ulcerative colitis. Elevated associated higher levels proteins sphingomyelins (SM) lower acids, amino triacylglycerols (TG). Relative patient remission, active state characterized by decreased SMs increased TGs. Treatment escalation augmented response-related reduced acids. Most TG species post-treatment Moreover, needed-treatment-escalation had significantly TGs (V). They also showed signaling receptor binding proteins. Multi-omics revealed biosignatures that captured groups each scenario. Eight analytes, including NFASC, ANGPTL4, chenodeoxycholate, found at least three Collectively, immune response, homeostasis, lipids alteration potentially underlie clinically IBD.

Language: Английский

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