Surrogate markers of intestinal dysfunction associated with survival in advanced cancers

Deviations in the diversity and composition of the gut microbiota are called “gut dysbiosis”. They have been linked to various chronic diseases including cancers and resistance to immunotherapy. Stool shotgun based-metagenomics informs on the ecological composition of the gut microbiota and the prev...

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Main Authors: Roxanne Birebent, Damien Drubay, Carolina Alves Costa Silva, Federica Marmorino, Giacomo Vitali, Gianmarco Piccinno, Yoan Hurtado, Adele Bonato, Lorenzo Belluomini, Meriem Messaoudene, Bertrand Routy, Marine Fidelle, Gerard Zalcman, Julien Mazieres, Clarisse Audigier-Valette, Denis Moro-Sibilot, François Goldwasser, Arnaud Scherpereel, Hervé Pegliasco, François Ghiringhelli, Anna Reni, Fabrice Barlesi, Laurence Albiges, David Planchard, Stéphanie Martinez, Benjamin Besse, Nicola Segata, Chiara Cremolini, Laurence Zitvogel, Valerio Iebba, Lisa Derosa
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:OncoImmunology
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Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2025.2484880
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author Roxanne Birebent
Damien Drubay
Carolina Alves Costa Silva
Federica Marmorino
Giacomo Vitali
Gianmarco Piccinno
Yoan Hurtado
Adele Bonato
Lorenzo Belluomini
Meriem Messaoudene
Bertrand Routy
Marine Fidelle
Gerard Zalcman
Julien Mazieres
Clarisse Audigier-Valette
Denis Moro-Sibilot
François Goldwasser
Arnaud Scherpereel
Hervé Pegliasco
François Ghiringhelli
Anna Reni
Fabrice Barlesi
Laurence Albiges
David Planchard
Stéphanie Martinez
Benjamin Besse
Nicola Segata
Chiara Cremolini
Laurence Zitvogel
Valerio Iebba
Lisa Derosa
author_facet Roxanne Birebent
Damien Drubay
Carolina Alves Costa Silva
Federica Marmorino
Giacomo Vitali
Gianmarco Piccinno
Yoan Hurtado
Adele Bonato
Lorenzo Belluomini
Meriem Messaoudene
Bertrand Routy
Marine Fidelle
Gerard Zalcman
Julien Mazieres
Clarisse Audigier-Valette
Denis Moro-Sibilot
François Goldwasser
Arnaud Scherpereel
Hervé Pegliasco
François Ghiringhelli
Anna Reni
Fabrice Barlesi
Laurence Albiges
David Planchard
Stéphanie Martinez
Benjamin Besse
Nicola Segata
Chiara Cremolini
Laurence Zitvogel
Valerio Iebba
Lisa Derosa
author_sort Roxanne Birebent
collection DOAJ
description Deviations in the diversity and composition of the gut microbiota are called “gut dysbiosis”. They have been linked to various chronic diseases including cancers and resistance to immunotherapy. Stool shotgun based-metagenomics informs on the ecological composition of the gut microbiota and the prevalence of homeostatic bacteria such as Akkermansia muciniphila (Akk), while determination of the serum addressin MAdCAM-1 instructs on endothelial gut barrier dysfunction. Here we examined patient survival during chemo-immuno-therapy in 955 cancer patients across four independent cohorts of non-small cell lung (NSCLC), genitourinary (GU) and colorectal (CRC) cancers, according to hallmarks of gut dysbiosis. We show that Akk prevalence represents a stable and favorable phenotype in NSCLC and CRC cancer patients. Over-dominance of Akk above the healthy threshold was observed in dismal prognosis in NSCLC and GU and mirrored an immunosuppressive gut ecosystem and excessive intestinal epithelial exfoliation in NSCLC. In CRC, the combination of a lack of Akk and low sMAdCAM-1 levels identified a subset comprising 28% of patients with reduced survival, independent of the immunoscore. We conclude that gut dysbiosis hallmarks deserve integration within the diagnosis toolbox in oncological practice.
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spelling doaj-art-6e73f92ec26c4a38b2dec9ee534602362025-08-20T02:26:23ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2484880Surrogate markers of intestinal dysfunction associated with survival in advanced cancersRoxanne Birebent0Damien Drubay1Carolina Alves Costa Silva2Federica Marmorino3Giacomo Vitali4Gianmarco Piccinno5Yoan Hurtado6Adele Bonato7Lorenzo Belluomini8Meriem Messaoudene9Bertrand Routy10Marine Fidelle11Gerard Zalcman12Julien Mazieres13Clarisse Audigier-Valette14Denis Moro-Sibilot15François Goldwasser16Arnaud Scherpereel17Hervé Pegliasco18François Ghiringhelli19Anna Reni20Fabrice Barlesi21Laurence Albiges22David Planchard23Stéphanie Martinez24Benjamin Besse25Nicola Segata26Chiara Cremolini27Laurence Zitvogel28Valerio Iebba29Lisa Derosa30Gustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceUnit of Medical Oncology 2, University Hospital of Pisa, Pisa, ItalyGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceDepartment CIBIO, University of Trento, Trento, ItalyGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceCentre Hospitalier de l’Université de Montréal (CHUM), Hematology-Oncology Division, Department of Medicine, Montréal, QC, CanadaCentre Hospitalier de l’Université de Montréal (CHUM), Hematology-Oncology Division, Department of Medicine, Montréal, QC, CanadaGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceThoracic Oncology Department-CIC1425/CLIP2 Paris-Nord, Bichat-Claude Bernard Hospital, AP-HP, Université Paris Cité, Paris, FranceService de Pneumologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, FrancePneumology Department, Centre Hospitalier Toulon Sainte-Musse, Toulon, FranceDepartment of Thoracic Oncology, Centre Hospitalier Universitaire, Grenoble, FranceINSERM U1016-CNRS UMR8104-Cochin Institute, Université Paris-Cité, Paris,FranceDepartment of Pulmonary and Thoracic Oncology, University of Lille, University Hospital (CHU), INSERM unit OncoThAI, Lille, FrancePulmonary Department, European Hospital, Marseille, FranceCancer Biology Transfer Platform, Centre Georges-François Leclerc, Dijon, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceService des Maladies Respiratoires, Centre Hospitalier d’Aix-en-Provence, Aix-en-Provence, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceDepartment CIBIO, University of Trento, Trento, ItalyUnit of Medical Oncology 2, University Hospital of Pisa, Pisa, ItalyGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceGustave Roussy Cancer Campus, ClinicObiome, Villejuif, FranceDeviations in the diversity and composition of the gut microbiota are called “gut dysbiosis”. They have been linked to various chronic diseases including cancers and resistance to immunotherapy. Stool shotgun based-metagenomics informs on the ecological composition of the gut microbiota and the prevalence of homeostatic bacteria such as Akkermansia muciniphila (Akk), while determination of the serum addressin MAdCAM-1 instructs on endothelial gut barrier dysfunction. Here we examined patient survival during chemo-immuno-therapy in 955 cancer patients across four independent cohorts of non-small cell lung (NSCLC), genitourinary (GU) and colorectal (CRC) cancers, according to hallmarks of gut dysbiosis. We show that Akk prevalence represents a stable and favorable phenotype in NSCLC and CRC cancer patients. Over-dominance of Akk above the healthy threshold was observed in dismal prognosis in NSCLC and GU and mirrored an immunosuppressive gut ecosystem and excessive intestinal epithelial exfoliation in NSCLC. In CRC, the combination of a lack of Akk and low sMAdCAM-1 levels identified a subset comprising 28% of patients with reduced survival, independent of the immunoscore. We conclude that gut dysbiosis hallmarks deserve integration within the diagnosis toolbox in oncological practice.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2484880Gut dysbiosisAkkermansiaMAdCAM-1biomarkerimmune checkpoint inhibitorschemotherapy
spellingShingle Roxanne Birebent
Damien Drubay
Carolina Alves Costa Silva
Federica Marmorino
Giacomo Vitali
Gianmarco Piccinno
Yoan Hurtado
Adele Bonato
Lorenzo Belluomini
Meriem Messaoudene
Bertrand Routy
Marine Fidelle
Gerard Zalcman
Julien Mazieres
Clarisse Audigier-Valette
Denis Moro-Sibilot
François Goldwasser
Arnaud Scherpereel
Hervé Pegliasco
François Ghiringhelli
Anna Reni
Fabrice Barlesi
Laurence Albiges
David Planchard
Stéphanie Martinez
Benjamin Besse
Nicola Segata
Chiara Cremolini
Laurence Zitvogel
Valerio Iebba
Lisa Derosa
Surrogate markers of intestinal dysfunction associated with survival in advanced cancers
OncoImmunology
Gut dysbiosis
Akkermansia
MAdCAM-1
biomarker
immune checkpoint inhibitors
chemotherapy
title Surrogate markers of intestinal dysfunction associated with survival in advanced cancers
title_full Surrogate markers of intestinal dysfunction associated with survival in advanced cancers
title_fullStr Surrogate markers of intestinal dysfunction associated with survival in advanced cancers
title_full_unstemmed Surrogate markers of intestinal dysfunction associated with survival in advanced cancers
title_short Surrogate markers of intestinal dysfunction associated with survival in advanced cancers
title_sort surrogate markers of intestinal dysfunction associated with survival in advanced cancers
topic Gut dysbiosis
Akkermansia
MAdCAM-1
biomarker
immune checkpoint inhibitors
chemotherapy
url https://www.tandfonline.com/doi/10.1080/2162402X.2025.2484880
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