AIRRWAS integrates TCR-microbiome data to reveal how the gut microbiome shapes the circulating and mucosal T cell repertoire

T cell receptor (TCR) sequencing with fecal 16S rRNA microbiome profiling and developed adaptive immune receptor repertoire-wide association study (AIRRWAS), a framework integrating computational TCR-microbiome interaction analysis with targeted in vitro validation. Across three independent cohorts, AIRRWAS identified reproducible associations between convergent TCR clusters and 21 bacterial genera, including core commensals, probiotics, and taxa with immunomodulatory roles. Predicted clonotypes were enriched in genus-specific interaction networks and preferentially activated by matched bacterial stimuli. These findings reveal conserved microbiome-driven immune signatures across distinct repertoires and demonstrate that the gut microbiome shapes both local and circulating T cell populations, providing a resource for biomarker discovery, immune monitoring, and microbiome-targeted therapies.

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Publication Details

Journal
Cell Reports
Published
2026-05-30
DOI
https://doi.org/10.1016/j.celrep.2026.117479
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
0.00

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article

AIRRWAS integrates TCR-microbiome data to reveal how the gut microbiome shapes the circulating and mucosal T cell repertoire

Ilke De Boeck, Naomi De Roeck, Esther Bartholomeus, Ting Pu et al.
Cell Reports
Gut microbiota and health
article

AIRRWAS integrates TCR-microbiome data to reveal how the gut microbiome shapes the circulating and mucosal T cell repertoire

Ilke De Boeck, Naomi De Roeck, Esther Bartholomeus, Ting Pu, Benson Ogunjimi, Pieter Meysman, Kris Laukens, Sara Verbandt, Mỹ Hà, Thies Gehrmann, Hajar Besbassi, Sarah Lebeer, Romi Vandoren, Fabio Affaticati, Vincent M.L. Van Deuren, Bas Oldenburg, Femke van Wijk, Eelco C. Brand, Peter Delputte, Sabine Tejpar, Maria Kuznetsova
article en

Abstract

T cell receptor (TCR) sequencing with fecal 16S rRNA microbiome profiling and developed adaptive immune receptor repertoire-wide association study (AIRRWAS), a framework integrating computational TCR-microbiome interaction analysis with targeted in vitro validation. Across three independent cohorts, AIRRWAS identified reproducible associations between convergent TCR clusters and 21 bacterial genera, including core commensals, probiotics, and taxa with immunomodulatory roles. Predicted clonotypes were enriched in genus-specific interaction networks and preferentially activated by matched bacterial stimuli. These findings reveal conserved microbiome-driven immune signatures across distinct repertoires and demonstrate that the gut microbiome shapes both local and circulating T cell populations, providing a resource for biomarker discovery, immune monitoring, and microbiome-targeted therapies.

Cell ReportsVol. 45(6)
University of Antwerp (BE), Utrecht University (NL), University Medical Center Utrecht (NL), Antwerp University Hospital (BE), Infectious Diseases Institute (UG), Biomedical Informatics Research Center Antwerp (BE), KU Leuven (BE)
Universitaire Stichting, Chan Zuckerberg Initiative, ZonMw, Fonds Wetenschappelijk Onderzoek, Vlaamse Interuniversitaire Raad, HORIZON EUROPE Reforming and enhancing the European Research and Innovation system
Zero hunger
Openalex Percentile: Top 9%
Gut microbiota and health
DOIOpen Access PDFOpenAlex
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