Small molecule metabolites: discovery of biomarkers and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

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Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 8, 2022

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints. Microbial infection considered crucial inducer of RA. Alterations in composition intestinal bacteria individuals with preclinical and established RA suggest vital role gut microbiota immune dysfunction characteristic However, mechanisms by which dysbiosis contributes to are not fully understood. Furthermore, multiple therapies commonly used treat may alter diversity, suggesting modulating help prevent or Hence, better understanding changes accompany should aid development novel therapeutic approaches. This mini-review discusses impact pathogenesis RA, selection microbiota-related biomarkers for diagnosing provides examples cross-modulation between some drugs Some suggestions outlooks also raised, guide future research efforts.

Language: Английский

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Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression

Journal of Autoimmunity, Journal Year: 2023, Volume and Issue: 141, P. 103001 - 103001

Published: March 15, 2023

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA prolonged state before clinical develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due the breakdown of immunologic self-tolerance. As early treatment initiation onset may achieve sustained remission, optimize outcomes, even prevent progression, pre-clinical stage showing prospect window opportunity for treatment. Growing evidence has shown role gut microbiota inducing systemic inflammation via multiple mechanisms, involve molecular mimicry, impaired intestinal barrier function, microbiota-derived metabolites mediated immune regulation, modulation microbiota's effect on cells, epithelial cells autophagy, interaction between microbiome human leukocyte antigen alleles as well microRNAs. Since alterations have been reported, potential therapies modifying RA, including natural products, antibiotic therapy, fecal transplantation, probiotics, microRNAs vitamin D supplementation, autophagy inducer-based treatment, prebiotics, diet, holds great promise successful prevention altering ongoing inflammation. In this review, we summarized current studies include pathogenesis progression promising therapeutic strategies provide novel ideas management possibly preventing progression.

Language: Английский

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The bridge of the gut–joint axis: Gut microbial metabolites in rheumatoid arthritis

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint destruction, synovitis, and pannus formation. Gut microbiota dysbiosis may exert direct pathogenic effects on gut homeostasis. It trigger the host’s innate immune system activate “gut–joint axis”, which exacerbates RA. However, although importance of in development progression RA widely recognized, mechanisms regulating interactions between host remain incompletely defined. In this review, we discuss role microbiota-derived biological mediators, such as short-chain fatty acids, bile tryptophan metabolites, maintaining intestinal barrier integrity, balance bone destruction patients bridge gut–joint axis.

Language: Английский

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Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 27, 2023

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by loss of immune tolerance and chronic inflammation. It pathogenesis complex includes interaction between genetic environmental factors. Current evidence supports the hypothesis that gut dysbiosis may play role triggers arthritis in animals humans. Progress understanding microbiome RA. has been remarkable last decade. In vitro vivo experiments revealed could shape system cause persistent inflammatory responses. Furthermore, induce alterations intestinal permeability, which have found to predate onset. contrast, metabolites derived from microbiota immunomodulatory anti-inflammatory effect. However, precise underlying mechanisms induces development remain elusive. This review aimed highlight contribute The overall data showed RA multiple pathways, including barrier function, molecular mimicry, influences activation differentiation innate acquired cells, cross-talk microbiota-derived microenvironment. relative weight each these remains uncertain. Recent studies a substantial for pathway, especially butyrate, pathogenesis.

Language: Английский

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Relationship between gut microbiota and rheumatoid arthritis: A bibliometric analysis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 1, 2023

Introduction Rheumatoid arthritis (RA) is a multifactorial autoimmune disease. Recently, growing evidence demonstrates that gut microbiota (GM) plays an important role in RA. But so far, no bibliometric studies pertaining to GM RA have ever been published. This study attempts depict the knowledge framework this field from holistic and systematic perspective based on analysis. Methods Literature related involvement of was searched picked Web Science Core Collection (WOSCC) database. The annual output, cooperation, hotspots, research status development trend were analyzed by software (VOSviewer Bibliometricx). Results 255 original articles 204 reviews included can be retrieved WOSCC first published 2004 increased year since then. 2013 growth explosion point. China United States are countries with most contributions, Harvard University affiliation output. Frontiers Immunology (total citations = 603) journal publications fastest rate. eLife 1248). Scher, Jose U. Taneja, Veena productive cited authors. mainly distributed evidence, mechanism practical application participating through analysis keywords documents. There sufficient prove close relationship between RA, which lays foundation for field. extended two colorful tender branches exploration, made some achievements but still broad exploration space. ”metabolites“, ”metabolomics“, ”acid“, ”b cells“, ”balance“, ”treg ”probiotic supplementation“ appeared frequently, tells us its hotspots recent years. Discussion Taken together, these results provide data-based objective introduction giving readers valuable reference help guide future research.

Language: Английский

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Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(706)

Published: July 26, 2023

Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity affects arthritis. To characterize community structure and associated functional processes driving microbial involvement arthritis, Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 diagnosed with rheumatoid ankylosing spondylitis, or psoriatic arthritis 219 healthy controls individuals joint pain without an underlying cause. Diagnosis explained about 2% taxonomic variability, is comparable magnitude bowel disease. We identified several candidate microbes differential carriage patterns patients elevated blood markers for inflammation. Our results confirm extend previous findings increased typically oral taxa decreased abundance prevalence typical clades, indicating that distal as well local correspond alterations composition. differentially encoded pathways including changes vitamin B salvage biosynthesis enrichment iron sequestration. Although these characteristic inflammation could causal roles, we hypothesize they are mainly positive feedback responses host physiology immune homeostasis. By connecting alternations alterations, this work expands our understanding shifts ecosystem occur response systemic during

Language: Английский

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Simulated Digestion and Fecal Fermentation Behaviors of Levan and Its Impacts on the Gut Microbiota

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(3), P. 1531 - 1546

Published: Jan. 9, 2023

Levan is a microbial fructan widely explored in various fields owing to its excellent physical and biochemical properties. However, little known about digestion fermentation characteristics vitro. This study evaluated the potential prebiotic properties of levan obtained by enzymatic synthesis. Scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy showed that primary structures remained stable after saliva-gastrointestinal digestion. The microtopography, molecular weight, functional group were seriously damaged during fecal fermentation. Moreover, total short-chain fatty acid levels increased significantly, especially for propionic acid, butyric valeric acid. 16S rDNA sequencing mainly abundance Firmicutes; genus levels, certain beneficial bacteria such as Megasphaera Megamonas genera remarkably promoted, proliferation harmful was inhibited (such Cedecea Klebsiella). Overall, this provided new insights into probiotic mechanism levan.

Language: Английский

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Microbiota-dependent indole production stimulates the development of collagen-induced arthritis in mice

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 134(4)

Published: Dec. 19, 2023

Altered tryptophan catabolism has been identified in inflammatory diseases like rheumatoid arthritis (RA) and spondyloarthritis (SpA), but the causal mechanisms linking metabolites to disease are unknown. Using collagen-induced (CIA) model, we alterations metabolism, specifically indole, that correlated with disease. We demonstrated both bacteria dietary were required for indole supplementation was sufficient induce their absence. When mice CIA on a low-tryptophan diet supplemented observed significant increases serum IL-6, TNF, IL-1β; splenic RORγt+CD4+ T cells ex vivo collagen-stimulated IL-17 production; pattern of anti-collagen antibody isotype switching glycosylation corresponded increased complement fixation. IL-23 neutralization reduced severity indole-induced CIA. Finally, exposure human colonic lymphocytes expression genes involved signaling plasma cell activation. Altogether, propose mechanism by which intestinal dysbiosis during results altered catabolism, leading stimulation development. Blockade generation may present unique therapeutic pathway RA SpA.

Language: Английский

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Impaired immune tolerance mediated by reduced Tfr cells in rheumatoid arthritis linked to gut microbiota dysbiosis and altered metabolites

Arthritis Research & Therapy, Journal Year: 2024, Volume and Issue: 26(1)

Published: Jan. 13, 2024

Abstract Background Patients with rheumatoid arthritis (RA) showed impaired immune tolerance characterized by reduced follicular regulatory T (Tfr) cells, and they also exhibited altered gut microbiotas their metabolites in RA. However, the association of mediated Tfr cells RA remains unclear. Methods Peripheral blood stool samples were collected from 32 new-onset patients 17 healthy controls (HCs) Second Hospital Shanxi Medical University between January 2022 June 2022. The peripheral was used to detect circulating (Treg), helper T(Th)17, Tfr, (Tfh) modified flow cytometry. analyze via 16S rDNA sequencing metabolomic profiling. We aimed characterize identified cell-mediated tolerance. Results demonstrated Treg associated disease activity autoantibodies. There significant differences two groups as results β diversity analysis ( P = 0.039) including 21 differential phylum genus levels. In which, Ruminococcus 2 autoantibodies RA, it potential biomarker [area under curve (AUC) 0.782, 95% confidence interval (CI) 0.636–0.929, 0.001]. Eleven participated four main pathways related Arachidonic acid might be (AUC 0.724, CI 0.595–0.909, 0.038), core metabolite positive six enriched , arachidonic involved biosynthesis unsaturated fatty pathway 3-methyldioxyindole tryptophan metabolism pathway. Conclusion breakdown implying possible mechanism pathogenesis perspective microecology-metabolism-immune.

Language: Английский

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