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 prevalence of homeostatic bacteria such as <i>Akkermansia muciniphila (</i>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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Publication Details

Journal
OncoImmunology
Published
2025-04-06
DOI
https://doi.org/10.1080/2162402x.2025.2484880
Citations
10
Primary Topic
Diet and metabolism studies
Type
article
Field-Weighted Citation Impact
11.64

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article

Surrogate markers of intestinal dysfunction associated with survival in advanced cancers

Marine Fidelle, Hervé Pegliasco, Gianmarco Piccinno, Benjamin Besse et al.
10 citations
OncoImmunology
Diet and metabolism studies
11.64
article

Surrogate markers of intestinal dysfunction associated with survival in advanced cancers

Marine Fidelle, Hervé Pegliasco, Gianmarco Piccinno, Benjamin Besse, Federica Marmorino, David Planchard, Denis Moro‐Sibilot, Adele Bonato, Bertrand Routy, François Ghiringhelli, Giacomo Vitali, Meriem Messaoudene, Anna Reni, Lisa Derosa, Julien Mazières, Gérard Zalcman, François Goldwasser, Nicola Segata, Valerio Iebba, Laurence Albigès, Laurence Zitvogel, Lorenzo Belluomini, Chiara Cremolini, Damien Drubay, Fabrice Barlési, Roxanne Birebent, Arnaud Scherpereel, Stéphanie Martinez, Clarisse Audigier-Valette, Carolina Alves Costa Silva, Yoan Hurtado
article en
10 citations

Abstract

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 <i>Akkermansia muciniphila (</i>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.

OncoImmunologyVol. 14(1)
University of Pisa (IT), University of Verona (IT), Inserm (FR), University of Trento (IT), Université Paris Cité (FR), Université de Lille (FR), Université Paris-Saclay (FR), Institut Gustave Roussy (FR), Centre Hospitalier Universitaire de Toulouse (FR), Hôpital Cochin (FR), Centre Georges François Leclerc (FR), La Ligue Contre le Cancer (FR), Assistance Publique – Hôpitaux de Paris (FR), Centre de recherche en Epidémiologie et Santé des Populations (FR), Centre Hospitalier Intercommunal Aix-Pertuis (FR), Center for Translational Molecular Medicine (NL), Centre Hospitalier de l’Université de Montréal (CA), European Hospital (IT), Hôpital Bichat-Claude-Bernard (FR), Centre Hospitalier Intercommunal Toulon-La Seyne-sur-Mer (FR), Azienda Ospedaliera Universitaria Pisana (IT), European Institute of Oncology (IT)
H2020 European Research Council
Zero hunger
Openalex Percentile: Top 1%
Diet and metabolism studies
11.64
DOIOpen Access PDFOpenAlex
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