Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response DOI Open Access
Duaa Ahmed Elhag, Manoj Kumar,

Marwa Saadaoui

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 6966 - 6966

Published: June 23, 2022

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with highly heterogeneous presentation. It has relapsing and remitting clinical course that necessitates lifelong monitoring treatment. Although availability variety effective therapeutic options including immunomodulators biologics (such as TNF, CAM inhibitors) led to paradigm shift in treatment outcomes management IBD patients, some patients still either fail respond or lose their responsiveness therapy over time. Therefore, according recent Selecting Therapeutic Targets Bowel Disease (STRIDE-II) recommendations, continuous from symptomatic relief endoscopic healing along short- long-term responses are critical for providing tailored algorithm. Moreover, considering high unmet need novel approaches various new modulators cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors cytokines example IL-12/IL-23, IL-22, IL-36, IL-6 anti-adhesion migration strategies β7 integrin, sphingosine 1-phosphate receptors, stem cells), well microbial-based therapeutics decolonize bed buds fecal microbiota transplantation bacterial currently being evaluated different phases controlled trials. This review aims offer comprehensive overview available emerging patients. Furthermore, predictive biomarkers response therapies also discussed.

Language: Английский

Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease DOI
Benjamin M. Scott, Cristina Gutiérrez‐Vázquez, Liliana M. Sanmarco

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(7), P. 1212 - 1222

Published: June 28, 2021

Language: Английский

Citations

189
The Role of Gut Microbiota Biomodulators on Mucosal Immunity and Intestinal Inflammation DOI Creative Commons
Chiara Amoroso, Federica Perillo, Francesco Strati

et al.

Cells, Journal Year: 2020, Volume and Issue: 9(5), P. 1234 - 1234

Published: May 16, 2020

Alterations of the gut microbiota may cause dysregulated mucosal immune responses leading to onset inflammatory bowel diseases (IBD) in genetically susceptible hosts. Restoring homeostasis through normalization is now considered a valuable therapeutic approach treat IBD patients. The customization microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics and faecal transplantation, therefore support current therapies management. In this review, we will discuss recent advancements understanding host−microbe interactions basis promote homeostatic therapies. By considering dysbiosis as key feature for establishment chronic events, near future it be suitable design new cost-effective, physiologic, patient-oriented strategies treatment that can applied personalized manner.

Language: Английский

Citations

186
Chemically and Biologically Engineered Bacteria‐Based Delivery Systems for Emerging Diagnosis and Advanced Therapy DOI
Zhaoting Li, Yixin Wang, Jun Liu

et al.

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(38)

Published: Aug. 4, 2021

Abstract Bacteria are one of the main groups organisms, which dynamically and closely participate in human health disease development. With integration chemical biotechnology, bacteria have been utilized as an emerging delivery system for various biomedical applications. Given unique features such their intrinsic biocompatibility motility, bacteria‐based systems drawn wide interest diagnosis treatment diseases, including cancer, infectious kidney failure, hyperammonemia. Notably, at interface biotechnology bacteria, many research opportunities initiated, opening a promising frontier application. Herein, current synergy design principles systems, microbial modulation, clinical translation reviewed, with special focus on advances therapy.

Language: Английский

Citations

175
D-mannose suppresses macrophage IL-1β production DOI Creative Commons
Simone Torretta, Alessandra Scagliola, Luisa Ricci

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Dec. 11, 2020

Abstract D-mannose is a monosaccharide approximately hundred times less abundant than glucose in human blood. Previous studies demonstrated that supraphysiological levels of inhibit tumour growth and stimulate regulatory T cell differentiation. It not known whether metabolism affects the function non-proliferative cells, such as inflammatory macrophages. Here, we show suppresses LPS-induced macrophage activation by impairing IL-1β production. In vivo, mannose administration improves survival mouse model endotoxemia well decreases progression DSS-induced colitis. Phosphomannose isomerase controls response LPS-activated macrophages to D-mannose, which impairs raising intracellular mannose-6-phosphate levels. Such alterations result suppression succinate-mediated HIF-1α activation, imposing consequent reduction Il1b expression. Disclosing an unrecognized metabolic hijack our study points towards safe utilization effective intervention against conditions.

Language: Английский

Citations

170
Regulatory role of short-chain fatty acids in inflammatory bowel disease DOI Creative Commons
Zhilin Zhang, Huan Zhang, Tian Chen

et al.

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: May 11, 2022

Inflammatory bowel disease (IBD) comprises a group of chronic inflammatory disorders the gastrointestinal tract. Accumulating evidence shows that development IBD is always accompanied by dysbiosis gut microbiota (GM), causing decrease in prebiotic levels and an increase harmful metabolite levels. This leads to persistent immune response inflammation intestine, greatly impairing physiological function Short-chain fatty acids (SCFAs) are produced probiotic bacteria from fiber-rich diet cannot be digested directly. SCFAs with significant anti-inflammatory functions regulate prevent excessive response, thereby delaying clinical progression IBD. In this review, we summarize generation their potential therapeutic effects on Furthermore, suggest may modulate innate recognition cytokine production intervene Additional randomized controlled trials prospective cohort studies should also investigate impact SCFA. Video Abstract.

Language: Английский

Citations

145
Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome DOI Creative Commons
Cheng Kong, Xuebing Yan, Yongqiang Liu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: April 23, 2021

Abstract Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, consequences this unique diet on colitis remain unknown. We performed series systematic studies using dextran sulfate sodium (DSS) animal model inflammatory colitis. Animals were fed with KD, low-carbohydrate (LCD), or normal (ND). Germ-free mice utilized in validation experiments. Colon tissues analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, immunofluorescence. Serum samples metabolic assay kit. Fecal 16S rRNA gene liquid chromatography–mass spectrometry gas spectrometry. observed KD alleviated altering gut microbiota metabolites manner distinct from LCD. Quantitative experiments confirmed impact relative to LCD reproducible increase Akkermansia , whereas opposite was for Escherichia/Shigella . After induction, protected intestinal barrier function, reduced production RORγt + CD3 − group 3 innate lymphoid cells (ILC3s) related cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal transplantation into germ-free revealed KD- mediated inhibition ILC3 regulation dependent modification microbiota. Taken together, our study presents global view microbiome-metabolomics changes occur during treatment, identifies microbiome ILC3s as novel targets involving IBD dietary therapy.

Language: Английский

Citations

144
Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation DOI Creative Commons
Qi Lv, Xing Yao, Jian Liu

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 11(9), P. 2880 - 2899

Published: March 10, 2021

Aberrant activation of NLRP3 inflammasome in colonic macrophages strongly associates with the occurrence and progression ulcerative colitis. Although targeting has been considered to be a potential therapy, underlying mechanism through which pathway intestinal inflammation is modulated remains controversial. By focusing on flavonoid lonicerin, one most abundant constituents existed long historical anti-inflammatory anti-infectious herb Lonicera japonica Thunb., here we report its therapeutic effect by binding directly enhancer zeste homolog 2 (EZH2) histone methyltransferase. EZH2-mediated modification H3K27me3 promotes expression autophagy-related protein 5, turn leads enhanced autophagy accelerates autolysosome-mediated degradation. Mutations EZH2 residues (His129 Arg685) indicated dynamic simulation study have found greatly diminish protective lonicerin. More importantly, vivo studies verify that lonicerin dose-dependently disrupts NLRP3–ASC–pro-caspase-1 complex assembly alleviates colitis, compromised administration overexpression plasmid. Thus, these findings together put forth stage for further considering as an epigenetic agent suggesting EZH2/ATG5/NLRP3 axis may serve novel strategy prevent colitis well other inflammatory diseases.

Language: Английский

Citations

141
Bile Acid–Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside DOI Open Access
Min Yang, Yu Gu,

Lingfeng Li

et al.

Nutrients, Journal Year: 2021, Volume and Issue: 13(9), P. 3143 - 3143

Published: Sept. 9, 2021

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota bile acids play pivotal roles in intestinal homeostasis inflammation. Patients IBD exhibit decreased microbial diversity abnormal composition marked by depletion phylum Firmicutes (including bacteria involved acid metabolism) enrichment Proteobacteria. Dysbiosis leads to blocked transformation. Thus, concentration primary conjugated elevated at expense secondary IBD. In turn, could modulate community. Gut dysbiosis disturbed impair barrier immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal transplantation ursodeoxycholic acid, may alleviate restoring acids. acid-gut axis closely connected pathogenesis. Regulation this be novel option for treating

Language: Английский

Citations

125
Mechanisms of mucosal healing: treating inflammatory bowel disease without immunosuppression? DOI
Eduardo J. Villablanca, Katja Selin, Charlotte Hedin

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2022, Volume and Issue: 19(8), P. 493 - 507

Published: April 19, 2022

Language: Английский

Citations

123
The Role of Innate and Adaptive Immune Cells in the Pathogenesis and Development of the Inflammatory Response in Ulcerative Colitis DOI Open Access

Aleksandra Kałużna,

Paweł Olczyk, Katarzyna Komosińska‐Vassev

et al.

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(2), P. 400 - 400

Published: Jan. 13, 2022

Ulcerative colitis (UC) is a chronic inflammatory disease with an underlying excessive immune response directed against resident microbiota and/or dietary antigens. Both innate and adaptive cells play crucial role in the pathogenesis of UC. In case cells, neutrophils, dendritic macrophages have impact on development disease, as well lymphoid which received particular attention recent years. On other hand, mechanisms involve such as: cytotoxic lymphocytes, regulatory lymphocytes Treg, or helper Th–Th2, Th9, Th17, Th22, among significant discoveries about Th9 Th17 been made Due to presence antibodies one’s own tissues, influence B UC also highlighted. Additionally, cytokines shaping sustaining inflammation seems be crucial. This review briefly describes current state knowledge involvement systems The based personal selection literature that were retrieved by selective search PubMed using terms “ulcerative colitis” “pathogenesis ulcerative colitis”. It included systematic reviews, meta-analyses clinical trials. Our system pathophysiology IBD has advanced rapidly over last two decades, leading several immune-targeted treatments biological source, known biologic agents.

Language: Английский

Citations

118