Iranian journal of biotechnology · 2026
Analysis of Gut Microbiota Metabolites in Chronic Kidney Disease-Associated Pruritus Using Network Pharmacology and Molecular Docking.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Fu Xiaoyu, Xia Yu, Han Jing, Wang Wei, Zhang Boning, Liu Heyuan, Yang Xue, Han Shengnan, Zhang Chenggang
Аннотация
BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and distressing symptom in patients with renal dysfunction, yet its biological mechanisms are still not well defined. Growing evidence suggests that gut microbiota-derived metabolites may participate in systemic inflammatory regulation, providing a potential entry point for exploring CKD-aP pathogenesis.
OBJECTIVES: This study aimed to elucidate how gut microbial metabolites interact with host molecular targets involved in CKD-aP, and to identify candidate metabolites with therapeutic relevance through integrative bioinformatics approaches.
MATERIALS AND METHODS: Gut metabolite data were retrieved from the gutMGene database, and CKD-aP-related genes were collected from GeneCards, DisGeNET, and OMIM. Intersection targets were processed through STRING-based protein-protein interaction (PPI) analysis, followed by Gene Ontology and KEGG pathway enrichment using the DAVID platform. An integrated microbiota-substrate-metabolite-target (MSMT) network was constructed to visualize microbial-metabolic interactions. Key metabolites were subsequently examined by molecular docking to assess binding affinity with pivotal targets.
RESULTS: A total of 44 overlapping genes were identified between microbial metabolites and CKD-aP, among which IL6, AKT1, and PPARG were highlighted as major hub regulators. MSMT network analysis indicated strong associations among Lacticaseibacillus paracasei, tryptophan-related metabolites, and linoleic-acid-derived compounds in modulating CKD-aP. KEGG results emphasized pathways enriched in inflammatory and immune responses, including IL-17, C-type lectin receptor, and Toll-like receptor signaling. Docking simulations supported robust interactions for several metabolites, particularly 10-keto-12Z-octadecenoic acid with PPARG, Genipin with CASP3, and Urolithin A with CYP1A1.
CONCLUSION: Our findings suggest that gut microbial metabolites may alleviate CKD-aP by targeting IL6, AKT1, and PPARG through inflammatory signaling pathways. Notably, 10-keto-12Z-octadecenoic acid from Lacticaseibacillus paracasei demonstrates strong binding affinity with PPARG, highlighting the potential of probiotic-derived metabolites as novel therapeutic strategies for managing pruritus in chronic kidney disease patients.
OBJECTIVES: This study aimed to elucidate how gut microbial metabolites interact with host molecular targets involved in CKD-aP, and to identify candidate metabolites with therapeutic relevance through integrative bioinformatics approaches.
MATERIALS AND METHODS: Gut metabolite data were retrieved from the gutMGene database, and CKD-aP-related genes were collected from GeneCards, DisGeNET, and OMIM. Intersection targets were processed through STRING-based protein-protein interaction (PPI) analysis, followed by Gene Ontology and KEGG pathway enrichment using the DAVID platform. An integrated microbiota-substrate-metabolite-target (MSMT) network was constructed to visualize microbial-metabolic interactions. Key metabolites were subsequently examined by molecular docking to assess binding affinity with pivotal targets.
RESULTS: A total of 44 overlapping genes were identified between microbial metabolites and CKD-aP, among which IL6, AKT1, and PPARG were highlighted as major hub regulators. MSMT network analysis indicated strong associations among Lacticaseibacillus paracasei, tryptophan-related metabolites, and linoleic-acid-derived compounds in modulating CKD-aP. KEGG results emphasized pathways enriched in inflammatory and immune responses, including IL-17, C-type lectin receptor, and Toll-like receptor signaling. Docking simulations supported robust interactions for several metabolites, particularly 10-keto-12Z-octadecenoic acid with PPARG, Genipin with CASP3, and Urolithin A with CYP1A1.
CONCLUSION: Our findings suggest that gut microbial metabolites may alleviate CKD-aP by targeting IL6, AKT1, and PPARG through inflammatory signaling pathways. Notably, 10-keto-12Z-octadecenoic acid from Lacticaseibacillus paracasei demonstrates strong binding affinity with PPARG, highlighting the potential of probiotic-derived metabolites as novel therapeutic strategies for managing pruritus in chronic kidney disease patients.