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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) in cancer patients. However, the role of the intestinal barrier, which mutually interacts with the gut microbiota, in shaping anti-cancer immune responses has not been extensively studied so far. Therefore, the primary goal of our 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 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, 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, intestinal barrier functionality was associated with clinical outcomes of anti-PD-1 therapy in advanced melanoma patients. Future studies are warranted to elucidate whether intestinal barrier modification could improve ICI efficacy and estimate the clinical value and utility of biomarkers reflecting its state.
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 Adam
dc.contributor.authorSchmidt, Marcin
dc.date.access2025-10-16
dc.date.accessioned2025-10-23T11:10:14Z
dc.date.available2025-10-23T11:10:14Z
dc.date.copyright2025-06-16
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) in cancer patients. However, the role of the intestinal barrier, which mutually interacts with the gut microbiota, in shaping anti-cancer immune responses has not been extensively studied so far. Therefore, the primary goal of our 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 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, 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, intestinal barrier functionality was associated with clinical outcomes of anti-PD-1 therapy in advanced melanoma patients. Future studies are warranted to elucidate whether intestinal barrier modification could improve ICI efficacy and estimate the clinical value and utility of biomarkers reflecting its state.</jats:p>
dc.description.accesstimebefore_publication
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_nocost
dc.description.financecost0,00
dc.description.versionoriginal_author
dc.identifier.doi10.20944/preprints202506.1274.v1
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/5417
dc.identifier.weblinkhttps://www.preprints.org/manuscript/202506.1274/v1
dc.languageen
dc.relation.ispartofPreprints.org
dc.relation.pagesart. 2025061274
dc.rightsCC-BY
dc.sciencecloudnosend
dc.share.typeOPEN_REPOSITORY
dc.subject.enintestinal barrier
dc.subject.ensecretory immunoglobulin A
dc.subject.engut microbiota
dc.subject.enadvanced melanoma
dc.subject.enimmune checkpoint inhibitors
dc.subtypeArticleEarlyAccess
dc.titleCharacteristics of Intestinal Barrier State and Immunoglobulin-Bound Fraction of Stool Microbiota in Advanced Melanoma Patients Undergoing Anti-PD-1 Therapy
dc.typeJournalArticle
dspace.entity.typePublication