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Percorrer por autor "Crespo, Ricardo"

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  • miR-21-5p dysregulation is associated with gut microbiota dysbiosis and pro-oncogenic markers in primary sclerosing cholangitis with concomitant inflammatory bowel disease
    Publication . Santos, André Anastácio; Pires, David; Marques, Vanda; Alesina, Nicole; Rodrigues, Pedro Miguel; Bravo, Ana Catarina; Gouveia, Catarina; Saraiva, Susana; Correia, Luís; Crespo, Ricardo; Silva, João Pereira da; Cravo, Marília; Banales, Jesus Maria; Torres, Joana; Rodrigues, Cecília Maria Pereira
    Background: Primary sclerosing cholangitis (PSC) is a chronic liver disease frequently associated with inflammatory bowel disease (IBD) and increased risk of colorectal cancer (CRC). Despite the strong association, the underlying mechanisms linking PSC-IBD, gut inflammation, and neoplastic potential remain unclear. This study explores the role of miR-21-5p dysregulation, gut microbiota dysbiosis, and pro-oncogenic markers in shaping the inflammatory and neoplastic microenvironment in PSC-IBD patients. Methods: A case-control study was conducted, including PSC patients with concomitant IBD (n = 14) and control individuals without diagnosed PSC and IBD (n = 20). miR-21-5p levels were evaluated in serum, fecal samples, and colonic biopsies via qPCR. Gut microbiota composition was analyzed using 16S rRNA sequencing. Pro-oncogenic and inflammatory markers in colonic tissue were assessed via qPCR. In vitro studies were performed using cholangiocyte (H69), colorectal cancer (HCT116), and primary monocyte models to investigate the role of miR-21-5p. Results: miR-21-5p was significantly upregulated in the right colon, serum, and fecal samples of PSC-IBD patients compared to controls. Gut microbiota analysis revealed dysbiosis, characterized by an increased Bacteroidota/Bacillota ratio and reduction in bile acid-metabolizing bacteria, including Clostridium sensu stricto 1, Ruminococcaceae UCG-002, and Christensenellaceae_R7_group. Colonic tissue analysis showed increased expression of EMT-related transcription factors TWIST1 and SNAIL, inflammatory cytokines IL-8, CCL2, and COX2, and the stem cell marker LGR5. In vitro studies confirmed miR-21-5p role in upregulating does markers in monocytes and CRC cells. Conclusion: This study found a link between miR-21-5p dysregulation and gut microbiota dysbiosis, colonic inflammation, and pro-oncogenic signaling in PSC-IBD patients. These findings highlight miR-21-5p as a potential modulator of disease progression and neoplastic risk.
    2026-03-01Artigo de investigação Acesso aberto Ver mais
  • Primary bile acid shapes peripheral immunity in inflammatory bowel disease-associated primary sclerosing cholangitis
    Publication . Santos, André A.; Pires, David; Marques, Vanda; Alesina, Nicole; Herraez, Elisa; Roudnický, Pavel; Rodrigues, Pedro M.; Godinho-Santos, Ana; Bravo, Ana Catarina; Gouveia, Catarina; Saraiva, Susana; Correia, Luís; Crespo, Ricardo; Silva, João Pereira da; Cravo, Marília; Zdráhal, Zbyněk; Banales, Jesus M.; Marin, Jose J. G.; Torres, Joana; Rodrigues, Cecília M. P.; Potesil, David
    Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with underlying inflammatory bowel disease (IBD). This study investigates how PSC predisposes individuals to altered inflammatory immune responses compared with IBD alone. A case–control study was conducted with a cohort of 75 patients, including 16 with PSC (14 with concomitant IBD), 39 with IBD alone, and 20 controls. Serum bile acid profile, proteomic analysis, and immune-related gene expression in the colon tissue were examined. Colonic tissue from PSC patients exhibited up-regulation of immune regulation and inflammatory signaling mRNA markers, including LGR5, IL-8, CCL2, COX2, TWIST1, and SNAIL. Additionally, PSC patients displayed a distinct proinflammatory serum proteomic signature and moderate elevation of some bile acids, such as glycochenodeoxycholic acid (GCDCA). Co-incubation of human-derived monocytes with GCDCA partially replicated the inflammatory profile observed in PSC. These findings suggest that circulating bile acids modulate the peripheral immune system proinflammatory response, contributing to the unique PSC phenotype.
    2025-06-01Artigo de investigação Acesso aberto Ver mais