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Characteristics of Intestinal Barrier State and Immunoglobulin-Bound Fraction of Stool Microbiota in Advanced Melanoma Patients Undergoing Anti-PD-1 Therapy

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dc.abstract.enThe gut microbiota is recognized as one of the extrinsic factors that modulate the clinical outcomes of immune checkpoint inhibitors (ICIs), such as inhibitors targeting programmed cell death protein 1 (PD-1), in cancer patients. However, the link between intestinal barrier, which mutually interacts with the gut microbiota, and therapeutic effects has not been extensively studied so far. Therefore, the primary goal of this study was to investigate the relationship between intestinal barrier functionality and clinical outcomes of anti-PD-1 therapy in patients with advanced melanoma. Fecal samples were collected from 64 patients before and during anti-PD-1 therapy. The levels of zonulin, calprotectin, and secretory immunoglobulin A (SIgA), which reflect intestinal permeability, inflammation, and immunity, respectively, were measured in fecal samples (n = 115) using an Enzyme-Linked Immunosorbent Assay (ELISA). Moreover, the composition of the immunoglobulin (Ig)-bound (n = 108) and total stool microbiota (n = 117) was determined by the V3–V4 region of 16S rRNA gene sequencing. ELISA indicated a higher baseline concentration of fecal SIgA in patients with favorable clinical outcomes than those with unfavorable ones. Moreover, high baseline concentrations of intestinal barrier state biomarkers correlated with survival outcomes. In the cases of fecal zonulin and fecal SIgA, there was a positive correlation, while in the case of fecal calprotectin, there was a negative correlation. Furthermore, there were differences in the microbial profiles of the Ig-bound stool microbiota between patients with favorable and unfavorable clinical outcomes and their changes during treatment. Collectively, these findings indicate an association between intestinal barrier functionality and clinical outcomes of anti-PD-1 therapy in advanced melanoma patients.
dc.affiliationWydział Nauk o Żywności i Żywieniu
dc.affiliation.instituteKatedra Biotechnologii i Mikrobiologii Żywności
dc.contributor.authorDrymel, Bernadeta
dc.contributor.authorTomela, Katarzyna
dc.contributor.authorGalus, Łukasz
dc.contributor.authorOlejnik-Schmidt, Agnieszka
dc.contributor.authorMackiewicz, Jacek
dc.contributor.authorKaczmarek, Mariusz
dc.contributor.authorMackiewicz, Andrzej
dc.contributor.authorSchmidt, Marcin
dc.date.access2025-09-30
dc.date.accessioned2025-09-30T13:12:26Z
dc.date.available2025-09-30T13:12:26Z
dc.date.copyright2025-08-20
dc.date.issued2025
dc.description.abstract<jats:p>The gut microbiota is recognized as one of the extrinsic factors that modulate the clinical outcomes of immune checkpoint inhibitors (ICIs), such as inhibitors targeting programmed cell death protein 1 (PD-1), in cancer patients. However, the link between intestinal barrier, which mutually interacts with the gut microbiota, and therapeutic effects has not been extensively studied so far. Therefore, the primary goal of this study was to investigate the relationship between intestinal barrier functionality and clinical outcomes of anti-PD-1 therapy in patients with advanced melanoma. Fecal samples were collected from 64 patients before and during anti-PD-1 therapy. The levels of zonulin, calprotectin, and secretory immunoglobulin A (SIgA), which reflect intestinal permeability, inflammation, and immunity, respectively, were measured in fecal samples (n = 115) using an Enzyme-Linked Immunosorbent Assay (ELISA). Moreover, the composition of the immunoglobulin (Ig)-bound (n = 108) and total stool microbiota (n = 117) was determined by the V3–V4 region of 16S rRNA gene sequencing. ELISA indicated a higher baseline concentration of fecal SIgA in patients with favorable clinical outcomes than those with unfavorable ones. Moreover, high baseline concentrations of intestinal barrier state biomarkers correlated with survival outcomes. In the cases of fecal zonulin and fecal SIgA, there was a positive correlation, while in the case of fecal calprotectin, there was a negative correlation. Furthermore, there were differences in the microbial profiles of the Ig-bound stool microbiota between patients with favorable and unfavorable clinical outcomes and their changes during treatment. Collectively, these findings indicate an association between intestinal barrier functionality and clinical outcomes of anti-PD-1 therapy in advanced melanoma patients.</jats:p>
dc.description.accesstimeat_publication
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_nocost
dc.description.financecost0,00
dc.description.if4,9
dc.description.number16
dc.description.points140
dc.description.versionfinal_published
dc.description.volume26
dc.identifier.doi10.3390/ijms26168063
dc.identifier.issn1422-0067
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/5099
dc.identifier.weblinkhttps://www.mdpi.com/1422-0067/26/16/8063
dc.languageen
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.relation.pagesart. 8063
dc.rightsCC-BY
dc.sciencecloudnosend
dc.share.typeOPEN_JOURNAL
dc.subject.enintestinal barrier
dc.subject.ensecretory immunoglobulin A
dc.subject.engut microbiota
dc.subject.enadvanced melanoma
dc.subject.enimmune checkpoint inhibitors
dc.titleCharacteristics of Intestinal Barrier State and Immunoglobulin-Bound Fraction of Stool Microbiota in Advanced Melanoma Patients Undergoing Anti-PD-1 Therapy
dc.title.volumeSpecial Issue Molecular Basis and Treatment of Skin Diseases and Their Associated Complications (2nd Edition)
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.issue16
oaire.citation.volume26