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Volume 26
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Article

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

by
Bernadeta Drymel
1,*,
Katarzyna Tomela
2,
Łukasz Galus
3,
Agnieszka Olejnik-Schmidt
1,
Jacek Mackiewicz
3,4,
Mariusz Kaczmarek
2,4,
Andrzej Mackiewicz
2,4 and
Marcin Schmidt
1,*
1
Department of Biotechnology and Food Microbiology, Poznań University of Life Sciences, 60-627 Poznań, Poland
2
Department of Cancer Immunology, Poznań University of Medical Sciences, 61-866 Poznań, Poland
3
Department of Medical and Experimental Oncology, Institute of Oncology, Poznań University of Medical Sciences, 60-355 Poznań, Poland
4
Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, 61-866 Poznań, Poland
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(16), 8063; https://doi.org/10.3390/ijms26168063 (registering DOI)
Submission received: 12 June 2025 / Revised: 8 August 2025 / Accepted: 15 August 2025 / Published: 20 August 2025
(This article belongs to the Special Issue Molecular Basis and Treatment of Skin Diseases and Their Associated Complications (2nd Edition))
Review Reports Versions Notes

Abstract

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.
Keywords: intestinal barrier; secretory immunoglobulin A; gut microbiota; advanced melanoma; immune checkpoint inhibitors intestinal barrier; secretory immunoglobulin A; gut microbiota; advanced melanoma; immune checkpoint inhibitors

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MDPI and ACS Style

Drymel, B.; Tomela, K.; Galus, Ł.; Olejnik-Schmidt, A.; Mackiewicz, J.; Kaczmarek, M.; Mackiewicz, A.; Schmidt, M. Characteristics of Intestinal Barrier State and Immunoglobulin-Bound Fraction of Stool Microbiota in Advanced Melanoma Patients Undergoing Anti-PD-1 Therapy. Int. J. Mol. Sci. 2025, 26, 8063. https://doi.org/10.3390/ijms26168063

AMA Style

Drymel B, Tomela K, Galus Ł, Olejnik-Schmidt A, Mackiewicz J, Kaczmarek M, Mackiewicz A, Schmidt M. Characteristics of Intestinal Barrier State and Immunoglobulin-Bound Fraction of Stool Microbiota in Advanced Melanoma Patients Undergoing Anti-PD-1 Therapy. International Journal of Molecular Sciences. 2025; 26(16):8063. https://doi.org/10.3390/ijms26168063

Chicago/Turabian Style

Drymel, Bernadeta, Katarzyna Tomela, Łukasz Galus, Agnieszka Olejnik-Schmidt, Jacek Mackiewicz, Mariusz Kaczmarek, Andrzej Mackiewicz, and Marcin Schmidt. 2025. "Characteristics of Intestinal Barrier State and Immunoglobulin-Bound Fraction of Stool Microbiota in Advanced Melanoma Patients Undergoing Anti-PD-1 Therapy" International Journal of Molecular Sciences 26, no. 16: 8063. https://doi.org/10.3390/ijms26168063

APA Style

Drymel, B., Tomela, K., Galus, Ł., Olejnik-Schmidt, A., Mackiewicz, J., Kaczmarek, M., Mackiewicz, A., & Schmidt, M. (2025). Characteristics of Intestinal Barrier State and Immunoglobulin-Bound Fraction of Stool Microbiota in Advanced Melanoma Patients Undergoing Anti-PD-1 Therapy. International Journal of Molecular Sciences, 26(16), 8063. https://doi.org/10.3390/ijms26168063

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