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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Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota–gut–brain axis

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(4), P. 222 - 247

Published: Feb. 14, 2024

Crosstalk between gut and brain has long been appreciated in health disease, the microbiota is a key player communication these two distant organs. Yet, mechanisms through which influences development function of gut–brain axis remain largely unknown. Barriers present are specialized cellular interfaces that maintain strict homeostasis different compartments across this axis. These barriers include epithelial barrier, blood–brain barrier blood–cerebrospinal fluid barrier. ideally positioned to receive communicate microbial signals constituting gateway for gut–microbiota–brain communication. In Review, we focus on how modulation by can constitute an important channel Moreover, malfunction upon alterations composition could form basis various conditions, including often comorbid neurological gastrointestinal disorders. Thus, should unravelling molecular move from simplistic framing as 'leaky gut'. A mechanistic understanding barriers, especially during critical windows development, be aetiology The modulator This Review provides overview examines role disease.

Language: Английский

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Advances in Understanding the Human Gut Microbiota and Its Implication in Pediatric Celiac Disease—A Narrative Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(11), P. 2499 - 2499

Published: May 27, 2023

Celiac disease (CD) is a multifactorial disorder, defined by complex interplay of genetic and environmental factors. Both predisposition dietary exposure to gluten are essential factors in triggering CD. However, there proof that their presence necessary, but not sufficient, for development. Through gut microbiota modulation, several additional have shown potential role as co-factors CD pathogenesis. The aim this review illustrate the possible mechanisms stand behind microbiota's involvement Furthermore, we discuss manipulation's both preventative therapeutic option. available literature provides evidence even before onset, including cesarean birth formula feeding, well intestinal infection exposure, amplify risk genetically predisposed individuals, due influence on microbiome composition. Active was associated with elevated levels Gram-negative bacterial genera, Bacteroides, Escherichia, Prevotella, while beneficial bacteria such lactobacilli bifidobacteria were less abundant. Viral fungal dysbiosis has also been described CD, evidencing specific taxa alteration. A gluten-free diet (GFD) may improve clinical symptoms duodenal histopathology, persistence children under GFD urges need therapy. Probiotics, prebiotics, fecal microbial transplant demonstrated efficacy restoring eubiosis adult patients; however, safety adjunctive therapies pediatric patients needs further investigation.

Language: Английский

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Exploring the Role of the Gut Microbiota in Modulating Colorectal Cancer Immunity

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1437 - 1437

Published: Aug. 27, 2024

The gut microbiota plays an essential role in maintaining immune homeostasis and influencing the landscape within tumor microenvironment. This review aims to elucidate interactions between dynamics, with a focus on colorectal cancer (CRC). spans foundational concepts of immuno-microbial interplay, factors microbiome composition, evidence linking immunotherapy outcomes. Gut modulates anti-cancer immunity through several mechanisms, including enhancement surveillance modulation inflammatory responses. Specific microbial species their metabolic byproducts can significantly influence efficacy immunotherapies. Furthermore, diversity correlates clinical outcomes CRC, suggesting potential as valuable biomarker for predicting response immunotherapy. Conclusions: Understanding relationship responses offers novel therapeutic strategies development. not only influences natural history treatment CRC but also serves critical modulator activity. Further exploration into microbiome's could enhance effectiveness existing treatments guide development new modalities.

Language: Английский

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From gut to liver: unveiling the differences of intestinal microbiota in NAFL and NASH patients

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

Published: April 4, 2024

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized for its global prevalence and potential progression to more severe diseases such as non-alcoholic steatohepatitis (NASH). The gut microbiota plays a pivotal role in the pathogenesis of NAFLD, yet detailed characteristics ecological alterations microbial communities during from (NAFL) NASH remain poorly understood. Methods: In this study, we conducted comparative analysis composition individuals with NAFL elucidate differences characteristics. We utilized 16S rRNA sequencing compare intestinal among healthy control group (65 cases), (64 (53 cases). Random forest machine learning database validation methods were employed analyze data. Results: Our findings indicate significant decrease diversity flora NAFLD ( p < 0.05). At phylum level, high abundances Bacteroidetes Fusobacteria observed both patients, whereas Firmicutes less abundant. genus Prevotella expression was seen (AUC 0.738), an increase combination Megamonas Fusobacterium noted 0.769). Furthermore, KEGG pathway highlighted disturbances various types glucose metabolism pathways compared group, well notably compromised flavonoid flavonol biosynthesis functions. study uncovers distinct microecological changes within transition NASH, providing insights that could facilitate discovery novel biomarkers therapeutic targets NAFLD.

Language: Английский

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Metabolomics and lipidomics signature in celiac disease: a narrative review

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 10, 2024

Abstract Celiac disease (CD) is a chronic immune-mediated inflammatory of the small intestine caused by aberrant immune responses to consumed gluten proteins. CD diagnosed combination patients reported symptoms, serologic and endoscopic biopsy evaluation intestine; adherence strict gluten-free diet (GFD) considered only available therapeutic approach for this disorder. Novel approaches need be finding new biomarkers help disorder diagnosis alternative method group patients. Metabolomics lipidomics are powerful tools provide highly accurate sensitive biomarkers. Previous studies indicated metabolic fingerprint deriving from alterations in gut microflora or intestinal permeability, malabsorption, energy metabolism. Moreover, since characterized increased permeability due importance membrane lipid components controlling barrier integrity, conducting great importance. In current study, we tried critical overview metabolomic lipidomic changes CD.

Language: Английский

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Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut

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

Published: Sept. 26, 2023

Human leukocyte antigen (HLA) genes are associated with more diseases than any other region of the genome. Highly polymorphic HLA produce variable haplotypes that specifically correlated pathogenically different autoimmunities. Despite differing etiologies, however, many autoimmune disorders share same risk-associated often resulting in comorbidity. This shared risk remains an unanswered question field. Yet, several groups have revealed links between gut microbial community composition and diseases. Autoimmunity is frequently dysbiosis, loss barrier function permeability tight junctions, which increases class II expression levels thus further influences microbiome. However, autoimmune-risk-associated connected to dysbiosis long before autoimmunity even begins. review evaluates current research on HLA-microbiome-autoimmunity triplex proposes pre-autoimmune bacterial important determinant comorbidities systemic inflammation as a common denominator.

Language: Английский

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Li-Hong Tang alleviates dextran sodium sulfate-induced colitis by regulating NRF2/HO-1 signaling pathway and gut microbiota

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

Published: May 30, 2024

Ulcerative colitis (UC) is marked by recurring inflammation. Existing treatments are ineffective and may have toxic side effects. Thus, new therapeutic agents urgently needed. We studied the botanical formula "Li-Hong Tang (LHT)", which contains two main ingredients,

Language: Английский

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NIAID workshop on infections and autoimmune diseases

Nature Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Language: Английский

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Children who develop celiac disease are predicted to exhibit distinct metabolic pathways among their gut microbiota years before diagnosis

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

ABSTRACT Celiac disease (CD) is an autoimmune caused by a loss of gluten tolerance in genetically predisposed individuals. While 30%–40% people possess the predisposing alleles, only 1%–2% are diagnosed with CD, suggesting that environmental factors involved pathogenesis. To determine association between pediatric CD and gut microbiome, we analyzed fecal samples from prospective cohort study (ABIS). These were collected children who later developed (CD progressors) age-matched healthy (at ages 1, 2.5, 5) similar HLA genotypes, breastfeeding durations, exposure times. We previously reported microbiome differences at 2.5 5 this cohort; here, present findings age 1 ( n = 5). identified 14 ASVs differing significantly progressors controls, including taxa linked to had increased Firmicutes higher alpha diversity IgA− bacteria. Using PICRUSt, metabolic pathways enriched compared controls 5–16), revealing inflammatory pathogenic potentially contributing CD-related immune dysregulation. results based on primary EdgeR analysis, also applied non-parametric method statistical reporting those supplementary figures. In conclusion, our suggest distinct years before diagnosis, which could inform targeted therapeutics for CD. As discussed limitations section, small pilot should be replicated larger sample sizes broader generalization. IMPORTANCE data celiac first life. corresponding three phases development, uncovered functional microbial 1. Some these pathways, implicated bacterial pathogenesis, microbiota modulation, inflammation, have been correlated Lachnospiraceae , Alistipes Bifidobacterium dentium associated potential role onset highlighting early interventions. exploratory validated sizes, suggests related onset, enhancing understanding pathogenesis microbiome-mediated alterations.

Language: Английский

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